Glucose Intolerance - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

GLUCOSE

INTOLERANCE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Glucose Intolerance: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00486-0 1. Glucose Intolerance-Popular works.I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on glucose intolerance. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON GLUCOSE INTOLERANCE .......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glucose Intolerance....................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 47 The National Library of Medicine: PubMed ................................................................................ 48 CHAPTER 2. NUTRITION AND GLUCOSE INTOLERANCE ................................................................ 93 Overview...................................................................................................................................... 93 Finding Nutrition Studies on Glucose Intolerance...................................................................... 93 Federal Resources on Nutrition ................................................................................................... 95 Additional Web Resources ........................................................................................................... 96 CHAPTER 3. ALTERNATIVE MEDICINE AND GLUCOSE INTOLERANCE .......................................... 97 Overview...................................................................................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 97 Additional Web Resources ......................................................................................................... 104 General References ..................................................................................................................... 104 CHAPTER 4. PATENTS ON GLUCOSE INTOLERANCE ..................................................................... 107 Overview.................................................................................................................................... 107 Patents on Glucose Intolerance.................................................................................................. 107 Patent Applications on Glucose Intolerance .............................................................................. 110 Keeping Current ........................................................................................................................ 111 CHAPTER 5. BOOKS ON GLUCOSE INTOLERANCE ........................................................................ 113 Overview.................................................................................................................................... 113 Book Summaries: Federal Agencies............................................................................................ 113 Chapters on Glucose Intolerance................................................................................................ 115 CHAPTER 6. MULTIMEDIA ON GLUCOSE INTOLERANCE .............................................................. 123 Overview.................................................................................................................................... 123 Video Recordings ....................................................................................................................... 123 CHAPTER 7. PERIODICALS AND NEWS ON GLUCOSE INTOLERANCE ........................................... 125 Overview.................................................................................................................................... 125 News Services and Press Releases.............................................................................................. 125 Academic Periodicals covering Glucose Intolerance .................................................................. 127 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 131 Overview.................................................................................................................................... 131 NIH Guidelines.......................................................................................................................... 131 NIH Databases........................................................................................................................... 133 Other Commercial Databases..................................................................................................... 135 APPENDIX B. PATIENT RESOURCES ............................................................................................... 137 Overview.................................................................................................................................... 137 Patient Guideline Sources.......................................................................................................... 137 Finding Associations.................................................................................................................. 139 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 143 Overview.................................................................................................................................... 143 Preparation................................................................................................................................. 143 Finding a Local Medical Library................................................................................................ 143 Medical Libraries in the U.S. and Canada ................................................................................. 143 ONLINE GLOSSARIES................................................................................................................ 149 Online Dictionary Directories ................................................................................................... 149

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GLUCOSE INTOLERANCE DICTIONARY ............................................................................ 151 INDEX .............................................................................................................................................. 209

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with glucose intolerance is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about glucose intolerance, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to glucose intolerance, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on glucose intolerance. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to glucose intolerance, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on glucose intolerance. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON GLUCOSE INTOLERANCE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glucose intolerance.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glucose intolerance, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “glucose intolerance” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Glucose Intolerance and Insulin Resistance in Aging is Related to Abdominal Obesity Source: Diabetes Spectrum. 6(4): 262-263. July-August 1993. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: In this article, the author considers recent findings that glucose intolerance and insulin resistance in aging are related to abdominal obesity. She stresses that some conditions often thought of as inevitable results of aging may instead be avoidable effects of fat accumulation. Topics include abdominal fat as a risk factor for developing glucose intolerance, insulin resistance, dyslipidemia, and hypertension; the link

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between abdominal obesity and the development of NIDDM and cardiovascular disease (CVD); sex and age factors; modest changes in body composition and their effects on glucose metabolism; the relationship between deteriorations in glucose tolerance and insulin resistance; and the possibility that monitoring a simple measure, such as waist size, may lead to early recognition of risk for NIDDM and CVD. 10 references. •

Renal Disease, Insulin Resistance, and Glucose Intolerance Source: Diabetes Reviews. 2(1): 19-28. Winter 1994. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: The author of this review article examines evidence of abnormal insulin action in renal diseases, underlying mechanisms, and potential pathogenetic implications. Hypotheses and controversies are analyzed, and potential areas of further research are identified. The author also discusses the clinical impact of these hormonal disturbances. Specific topics include the factors implicated in the pathogenesis of chronic renal failure (CRF), such as uremic toxins, exercise tolerance, metabolic acidosis, vitamin D deficiency, and anemia; the cellular basic of insulin resistance; glucose intolerance and insulin secretion in CRF; and the clinical implications of insulin abnormalities in CRF, including cardiovascular, metabolic, nutritional, and growth complications. 8 figures. 3 table. 58 references. (AA-M).

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Age and Glucose Intolerance: Effect of Fitness and Fatness. (editorial) Source: Diabetes Care. 26(2): 539-540. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: The fact that glucose intolerance increases with age has been apparent for over 30 years, leading to the suggestion at one time that the diagnostic criteria for diabetes be amended to account for this inevitable consequence of the aging process. However, these earlier findings did not differentiate the effects on the plasma glucose response to an oral glucose challenge of age per se from those due to the impact of a number of age-related variables. This editorial serves as an introduction to an article that provides additional information concerning the effect of body fat on glucose tolerance, as apparently healthy volunteers grow older. However, the editorial author notes that the potential effect of differences in fitness, an age-related variable of comparable magnitude, was apparently not considered in their study. The author concludes that loss of glucose tolerance with age is primarily related to weight gain and sedentary lifestyle, and level of physical activity is as powerful a factor as adiposity (body fat deposits) in this regard. The best way to stem the rapidly growing epidemic of type 2 diabetes is by concerted efforts beginning at a young age to prevent fatness and encourage fitness. 17 references.

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Insulin and Hypertension: Relationship to Obesity and Glucose Intolerance in Pima Indians Source: Diabetes. Volume 39: 1430-1435. November 1990. Summary: The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2,873 Pima Indians aged 18 to 92 years. Age-and sex-adjusted to the Pima population, the prevalence of hypertension was 7.1 percent for subjects with normal glucose tolerance, compared with 13.0 percent for

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subjects with impaired glucose tolerance, and 19.8 percent for those with noninsulindependent diabetes mellitus (NIDDM). The authors conclude that insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians. 5 figures. 4 tables. 59 references. (AA-M). •

Low Birth Weight, Family History of Diabetes, and Glucose Intolerance in Swedish Middle-Aged Men Source: Diabetes Care. 22(7): 1043-1047. July 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: This article describes a population based, cross sectional study that investigated the influence of family history of diabetes on the association between low birth weight and glucose intolerance. The study population consisted of 2,237 men born from 1938 to 1957 in four municipalities at the outskirts of Stockholm, Sweden. Fifty of the men had a family history of diabetes. Oral glucose tolerance testing detected 35 cases of type 2 diabetes, 102 cases of impaired glucose tolerance, and 57 cases of impaired fasting glucose. The study found that men whose birth weight was less than or equal to 3,000 grams were more than four times as likely to have diabetes as men whose birth weight was greater than or equal to 3,601 grams. For impaired glucose tolerance and impaired fasting glucose, the corresponding estimates were 1.9 and 2.6, respectively. In subjects with a family history of diabetes, the corresponding figures were approximately similar, except for diabetes, for which the odds ratio was 5.4. For men who had low birth weight in combination with a family history of diabetes, the odds ratio was 10.9 for diabetes, 2.4 for impaired glucose tolerance, and 5.9 for impaired fasting glucose. The article concludes that low birth weight is an important determinant of glucose intolerance but that the combination of low birth weight and family history of diabetes is particularly important to the risk of developing diabetes. 4 tables. 28 references. (AAM).

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Gestational Diabetes: Antepartum Characteristics That Predict Postpartum Glucose Intolerance and Type 2 Diabetes in Latino Women Source: Diabetes. 47(8): 1302-1310. August 1998. Summary: This article describes a study that examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks of gestation and returned between 1 and 6 months postpartum for a 75-gram OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. Results revealed that, at postpartum testing, 40 percent of the cohort had normal glucose tolerance, 50 percent had IGT, and 10 percent had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were

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the 30-minute incremental insulin:glucose ratio during a 75-gram OGTT and the total area under the diagnostic 100-gram glucose tolerance curve. Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response, a diagnosis of GDM before 22 weeks of gestation, and weight gain between prepregnancy and the postpartum examination. All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the third trimester were associated with the risk of IGT or diabetes within 6 months after delivery. Results highlight the importance of pancreatic beta cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the third trimester in women with such a beta cell defect. 1 appendix. 5 figures. 3 tables. 36 references. (AA-M). •

Epidemiology of Glucose Intolerance and Gestational Diabetes in Women of Childbearing Age Source: Diabetes Care. 21(Supplement 2): B9-B13. August 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article examines epidemiological data on gestational diabetes mellitus (GDM) from several sources. Available data suggest that the frequency of diabetes in pregnancy is highly variable, generally reflecting the underlying pattern of type 2 diabetes in the particular population. Different ethnic groups in the same environmental setting experience widely variable risk. Impaired glucose tolerance is usually more prevalent than diabetes in women of childbearing age. Maternal age, overweight, parity, and family history of diabetes all predispose to GDM. Incidence is low in the absence of risk factors, suggesting that selective screening programs may be cost-effective. Adverse outcome may be more frequent in women with impaired glucose tolerance than in women with normal tolerance. Programs to reduce the incidence of subsequent type 2 diabetes in women who have GDM may be cost effective to health services and improve the quality of life for those concerned. The worldwide epidemic of glucose intolerance predicted by the latest World Health Organization studies will undoubtedly increase the burden of GDM, especially in developing countries. 3 figures. 6 tables. 24 references. (AA-M).

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Inverse Association Between Fish Intake and Risk of Glucose Intolerance in Normoglycemic Elderly Men and Women Source: Diabetes Care. 14(11): 935-941. November 1991. Summary: This article reports on a research study undertaken to examine the association of fish intake with the subsequent risk of impaired glucose tolerance and diabetes mellitus (glucose intolerance). In 1971, information about food intake was obtained by the cross-check dietary history method on 175 men and women aged 64 to 87 years who were normoglycemic and free of clinical diabetes. During the follow-up period from 1972 to 1975, an oral glucose tolerance test was performed annually, and in 59 of 175 elderly people a diagnosis of glucose intolerance was made at least once. The results showed that in fish eaters, the incidence of glucose intolerance was significantly lower compared with nonfish eaters. The authors conclude that, in an elderly population, the habitual consumption of a small amount of fish may protect against the

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development of impaired glucose tolerance and diabetes mellitus. 6 tables. 49 references. (AA-M). •

Hypercholesterolemia in Diabetes and Glucose Intolerance in the U.S. Population Source: Diabetes Care. 14(5): 366-374. May 1991. Summary: This article reports on the prevalence of hypercholesterolemia, according to the guidelines of the National Cholesterol Education Program, which has been determined in a national survey of diabetes and glucose intolerance. Rates of elevated total cholesterol in people with diabetes in the United States are only slightly greater than in those without diabetes after adjusting for age and sex. Nevertheless, high or borderline high total cholesterol is common in diabetes and is present in 70 percent of adults with diagnosed diabetes and 77 percent with undiagnosed diabetes. The authors discuss the findings as they apply to risks for coronary heart disease. The authors conclude that investigation of blood lipid levels and coronary heart disease risk factors should be routine in all patients with diabetes, and treatment strategies should include management of lipid disorders and the multiple other risk factors for coronary heart disease that are highly prevalent in these patients. 2 figures. 7 tables. 50 references. (AAM).

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Long-Term (5-Year) Effects of a Reduced-Fat Diet Intervention in Individuals with Glucose Intolerance Source: Diabetes Care. 24(4): 619-624. April 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article reports on a study that determined whether reducing dietary fat would reduce body weight and improve long term glycemia in people with glucose intolerance. The study design was a 5 year follow up of a 1 year randomized controlled trial of a reduced fat ad libitum diet versus a usual diet. Participants with glucose intolerance were recruited from a Workforce Diabetes Survey conducted in 41 work sites around Auckland, New Zealand, between 1988 and 1990. The group that was randomized to a reduced fat diet participated in monthly small group education sessions on reduced fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline, 6 months, and 1 year, with follow up at 2 years, 3 years, and 5 years. Of the 136 participants who completed the 1 year intervention, 103 were reassessed at 5 years. The study found that, compared with the control group, weight decreased in the reduced fat diet group. The greatest difference was noted at 1 year, diminished at subsequent follow up, and was no longer present by 5 years. Glucose tolerance also improved in patients on the reduced fat diet. A lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year, but in subsequent years, there were no differences between groups. However, the more compliant 50 percent of the intervention group maintained lower fasting 2 hour glucose at 5 years compared with control subjects. The article concludes that the natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake. 2 figures. 3 tables. 26 references. (AA-M).

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Federally Funded Research on Glucose Intolerance The U.S. Government supports a variety of research studies relating to glucose intolerance. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to glucose intolerance. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore glucose intolerance. The following is typical of the type of information found when searching the CRISP database for glucose intolerance: •

Project Title: CAH: CALCIUM CHANNELS AS THERAPEUTIC TARGETS Principal Investigator & Institution: Loechner, Karen J.; Professor; Pediatrics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): This K08 application under the co-mentorship of Drs. Bob Rosenberg and Gerry Oxford has two goals: 1) to understand the cellular mechanisms that underlie coupling of voltage-activated calcium channels to regulated peptide secretion in the anterior pituitary, and 2) to assess the clinical impact of targeted calcium channel blockade in Congenital Adrenal Hyperplasia (CAH), a disorder resulting from pituitary hypersecretion. In studies of a pituitary corticotroph cell line (AtT-20) I identified three distinct high voltage-activated calcium channels that are expressed in similar abundance. Despite this, only the L-type [dihydropyridine (DHP)sensitive] channel is capable of triggering calcium-dependent secretion of ACTH. The primary focus of this proposal, therefore, is to examine the mechanisms that underlie the coupling of DHP-sensitive channels to ACTH release. I hypothesize that differential localization of the L-type channels accounts for the distinct function of the neurosecretory apparatus in ACTH-secreting cells. I propose to: a) examine the cellular sites of calcium channels and synaptic components using immunocytochemistry/ confocal microscopy, and b) disrupt coupling using a dominant-negative approach. In CAH, the most common adrenal disorder in children, a molecular defect in cortisol production removes normal negative feedback to the anterior pituitary and results in elevated ACTH secretion. Elevated ACTH further increases cortisol precursors, and shunts these steroid intermediates to androgen synthetic pathways. The clinical stigmata (e.g., ambiguous genitalia, virilization and short stature in adults) are due to the excess in androgens. Treatment requires life-long glucocorticoid replacement to restore the normal feedback mechanism. Determining the "optimal level" ofglucocorticoid replacement, however, is difficult: under-treatment leads to adrenal insufficiency and androgen excess; over-treatment leads to glucocorticoid excess (e.g., obesity, glucose intolerance and osteopenia). My work with the pituitary cells in culture suggests that

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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selective pharmacologic blockade of L-type (DHP-sensitive) channels, and, in turn, attenuation of ACTH release, will provide a novel adjunct therapy by allowing lower glucocorticoid dosing. This would result in enhanced linear growth and improved bone mineral density. These basic research and clinical studies complement one another, and together, they should enhance our understanding of the cellular mechanisms underlying peptide secretion. Furthermore, they may allow for improved treatment in hypersecretory conditions, such as CAH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR HEALTH IN CHILDREN AND YOUTH (CHIC III) Principal Investigator & Institution: Harrell, Joanne S.; Professor; None; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-MAR-1990; Project End 30-JUN-2004 Summary: This continuation of the Cardiovascular Health in Children and Youth Study (CHIC III) will investigate the childhood development of several risk factors for cardiovascular disease (CVD) and the aggregation of those risk factors over time. One recognized aggregation, or cluster, of risk factors is commonly linked to Type 2 diabetes and CVD in adults. This aggregation is called the insulin resistance syndrome and consists of related metabolic abnormalities including dyslipidemia (high triglyceride and low high density lipoprotein cholesterol [HDL-C], hypertension, hyperinsulinemia, and glucose intolerance). Obesity is thought by some to also be a part of the syndrome. At this time, little is known about the prevalence or development of the insulin resistance syndrome during childhood and adolescence. In addition, no studies have examined insulin resistance in youth with regard to eating habits, physical activity and maturational level, all of which can affect various risk factors, particularly those in the insulin resistance syndrome. Using an accelerated, longitudinal (cohort-sequential) design, CHIC II subjects and additional adolescent and preadolescent children will be followed through all stages of puberty. CVD risk factors as well as aggregation of specific factors into the insulin resistance syndrome will be studied. The contribution of obesity, heredity and environmental factors (broadly defined), as well as a newer risk factor (lipid particle subclass profiles), will also be examined to determine their effects on the emergence, aggregation and developmental course of risk factors for CVD. Youth in three cohorts, aged 8-18, will be evaluated annually for risk factors of CVD for 4 years or until they graduate from high school. We will measure: blood pressure; body mass index; skinfolds; waist and other circumferences; insulin, glucose, and lipids via venipuncture; CV fitness; eating habits; physical activity; and smoking to examine the emergence, aggregation and developmental course of risk factors across all stages of puberty. We will also store all blood for possible future genetic studies as well as gather data from parents on the family history of CVD and their personal health habits. This is a cost effective way to obtain these data, as we will be able to capitalize on the data already collected for CHIC II subjects. Major analysis will include general linear models and latent class models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOVASCULAR RISK IN SECOND GENERATION SOUTH ASIAN AME Principal Investigator & Institution: Agarwal, Simi; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2002 Summary: Several studies from the United States, South Africa and the United Kingdom have documented an increased risk of cardiovascular disease in immigrants from the Indian subcontinent when compared to people of European orgin. Several risk factors have been identified as increased in South Asian immigrants including lipoprotein (a), insulin resistance and glucose intolerance, truncal obesity, and total cholesterol:HDL ratio. Furthermore, both anecdotal and scientific evidence shows an increased morbidity from cardiovascular events in South Asian males. There have not been, however, any studies to date assessing the risk factors of cardiovascular morbidity in second generation South Asians born in the United States. The objective of this study is to determine whether second generation American-born South Asians have poorer prognostic cardiovascular risk profiles compared to white Americans. The reason this question is important is that it is unclear what the relationship is between the risk for heart disease someone inherits from his/her parents and the risk for heart disease which may come about by living in a particular environment. In order to understand this relationship, we will recruit a group of American born South Asians aged 18-30 who are children of immigrants, and a group of American born whites aged 18-30. Through these 18-30 year olds, we will be able to enlist the participation of their parents aged 4570. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZING AND MAPPING OBESITY AND DIABETES GENES Principal Investigator & Institution: Naggert, Juergen K.; Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2004 Summary: Non insulin dependent diabetes mellitus (NIDDM) is a major health problem which affects an estimated 5-10 percent of the American population. Although NIDDM is highly heritable in humans, its inheritance does not follow simple Mendelian laws and is, therefore, thought to be caused by the simultaneous action of many genes. Because such polygenic inheritance is still very difficult to unravel, single gene mutant models offer significant advantages for gene identification and for detailed physiological studies. Five recently cloned single gene obesity mutations in mouse have provided exciting new insights into the etiology of obesity. In contrast, identification of NIDDM genes is delayed, because single gene mouse mutations for NIDDM are lacking. We have identified a new mouse model for maturity onset NIDDM, which apparently is due to a recessive single gene mutation, that has provisionally been named sugar baby (sub). The Tallyho-sub/sub mouse stock is characterized by glucose intolerance, hyperinsulinemia, chronic hyperglycemia, and increased body weight. We have carried out a preliminary outcross to a nondiabetic, nonobese mouse strain to map the sub diabetes mutation. In this cross, in addition to the sub locus which determines plasma glucose levels, we were able to map a second locus, nicknamed 'brother of sub' (bos), which controls body weight. We also found evidence that the two loci interact epistatically, i.e. homozygosity at the bos locus is necessary for sub/sub mice to become diabetic. In contrast, homozygous bos/bos mice without the sub gene do not become diabetic. Based on our preliminary results, we hypothesize that the Tallyho strain carries a major obesity susceptibility allele (bos) that interacts with the sub mutation to produce the obese/diabetic phenotype of Tallyho-sub/sub mice. To test this hypothesis, we propose to carry out two specific aims. a.) to construct separate congenic lines of mice that carry either the bos and sub genes individually or in combination on a common

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genetic background and to use these lines to generate fine structure genetic maps for bos and sub in order to positionally clone these genes. b.) to physiologically characterize the Tallyho strain and the congenic lines and test the hypothesis that the sub gene can interact with obesity mutations other than bos to cause diabetes. At the successful conclusion of this work, we will have identified two new genes, bos and sub, that constitute an epistatic genetic system involved in the etiology of type II diabetes. Additionally, through examination of the mutations individually and in combination in a common genetic background, we will gain a better understanding of the pathways and physiological abnormalities that are necessary to cause diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHICAGO CHILDHOOD DIABETES REGISTRY Principal Investigator & Institution: Lipton, Rebecca B.; Associate Professor; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 30-SEP-1992; Project End 31-MAY-2008 Summary: (provided by applicant): Recent increases in childhood diabetes present an urgent public health challenge: to mount effective primary and secondary prevention efforts as soon as possible. We must therefore understand the mechanisms underlying the current epidemic, particularly the interaction of genetics with the changing epidemiology of behavioral risk factors. We propose to investigate the determinants of childhood diabetes risk in affected probands and their family members. This is a competing continuation application for the population-based Chicago Childhood Diabetes Registry. This database represents the largest number of non-Hispanic black children with diabetes worldwide, and the largest patient database for Latino children in the continental US. Ongoing ascertainment of incident cases will provide basic epidemiologic data and will anchor a further effort, in families of affected children, to describe the spectrum of youth-onset glucose intolerance in terms of inheritance and the expression of disease susceptibility alleles within families. We will specifically address these hypotheses: 1. That diabetes in youth is caused by a spectrum of etiologic processes, from the insulinopenia of autoimmune type 1 to obesity-related, insulinresistant type 2 diabetes. A subset of children demonstrate a mixed etiology, with autoimmune beta-cell destruction aggravated by the presence of insulin resistance due to genetic susceptibility, obesity and/or physical inactivity. 2. That secular changes in the epidemiology of childhood diabetes are directly related to changes in the prevalence of both type 1 and type 2 risk factors, including obesity, physical inactivity, and perinatal exposures. 3. That familial aggregation of specific traits affects the risk of chronic complications in young people with diabetes, over and above that of glycemic control. Ultimately, this approach will permit a truly population-based molecular epidemiologic study of early-onset diabetes in families from a range of ethnic groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTROL OF CAMP-MEDIATED GLUCAGON RESPONSE BY BILE ACIDS Principal Investigator & Institution: Bouscarel, Bernard E.; Associate Research Professor; Medicine; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: Cholestatic liver disease with cirrhosis in particular, is the 9th leading cause of death in the USA. Prognosis is poor, with a generally irreversible condition marked by progressive destruction of liver cells. Around 50 percent of patients with liver disease

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and 80 percent of cirrhotic patients display glucose intolerance associated with decreased gluconeogenic response to glucagon. Regulation of helpatocellular metabolism by glucagon is in part through increased cAMP synthesis. The central hypothesis is that certain bile acids alter the glucagon receptor-stimulatory G protein (Gs) coupling through a phosphorylation/dephosphorylation mechanism and that these alterations are responsible for attenuation and delayed recovery of glucagon responsiveness in cholestasis. We have shown that bile acids inhibit hepatic glucagoninduced cAMP synthesis at physiologic concentrations. The effect was at the level of receptor-Gs coupling, most likely through phosphorylation, and was mediated by a calcium-dependent PKC. We have reported that hepatic glucagon-mediated cAMP production was attenuated in cholestasis in hamster induced by ligation of the common bile duct (BDL). Bile acids were either without or with reduced effects after BDL suggesting that the site of cAMP synthesis cascade altered in cholestasis is the same as that altered by bile acids. Specific aims will test the hypotheses: 1)that short-term incubation of hepatocytes with bile acids leads to decreased glucagon receptor-Gs coupling through a phosphorylation/dephosphorylation mechanism involving PKC; 2)that alteration of both glucagon receptor-Gs coupling and receptor dephosphorylation are responsible for the respective attenuation and delayed recovery of glucagon responsiveness in cholestasis. In HEK293 clones expressing glucagon receptor, and in hepatocytes from BDL hamsters we will study the respective effect of physiologic/pathophysiologic bile acid concentrations and cholestasis on receptor/Gs coupling and phosphorylation using a multifaceted approach designed to determine the protein phosphorylation target. We will study the role of protein phosphatases on the time course of glucagon response recovery in cholestasis. Knowledge gained from these studies will have bearing on both diagnosis and treatment of cholestatic hepatobiliary disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--NUTRITION INTERVENTION Principal Investigator & Institution: Campbell, Marci K.; Associate Professor and Director, Cancer; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: (adapted from the application): We propose a CNRU that is specifically designed to enhance the translation of basic science information and technology into population-based and clinical nutrition research, and also to facilitate the transfer of ideas and information in the opposite direction. These population-based studies are the major approach for prevention research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures that typify nutrition versus drug studies. A major reason to locate a CNRU at UNC-CH is the strength and interdisciplinary breadth of our research programs in nutrition. Fifty-five active investigators conduct research that spans areas of basic, clinical and applied science relevant to human nutrition, including clinical nutrition, metabolic biochemistry, molecular biology, gastroenterology, hepatology, pharmacology, health behavior, nutrition epidemiology, physiology, oncology, and endocrinology. Excellent graduate students and postdoctoral fellows are working with CNRU investigators, and CNRU faculty are the awardees for four T32 training grants from the NIDDK, NHLBI, NIEHS and NCI. Our research base generates more than $20 million in annual NIH-funded (or equivalent) nutrition-related research support. CNRU faculty are appointed in many departments including nutrition, medicine, pharmacology, pediatrics, biostatistics,

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epidemiology, cell and molecular physiology, pathology, and environmental. Steven Zeisel, MD serves as CNRU director, and Rosalind Coleman, MD as associate director. An internal governance committee (consisting of the director, associate director, three core directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity and continuity of policies that govern the CNRU. An external advisory committee will be established. The Administrative Core will be responsible for management of the CNRU and will provide biostatistical support, grant pre-review services, facilitation of access to research populations, computer support, an enrichment program, a medical student education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a young investigator award, community outreach and public education. Several of these activities will be conducted in collaboration with the UNC-CH General Clinical Research Center. The proposed Translational Core for Population Studies, led by Lenore Kohlmeier, Ph.D., is designed to facilitate the translation of new findings and technology into ongoing research projects and to stimulate the incorporation of state of the art methodology in population based human nutrition studies. The core services will be in five areas: incorporation of biomarkers of dietary intake in ongoing studies, technical support in the preparation of multi-media based dietary assessment, statistical support in the design and analyses of epidemiological studies, support in the preparation of and access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of the Molecular Biology and Nutritional Biochemistry Core, directed by Melinda Beck, Ph.D., is to provide a state-of-the-art facility for nutrition research investigators. The Core will serve as an educational and training resource for the development and application of molecular biology techniques and biomarkers for nutritional research. It will provide a number of specialized techniques requested by CNRU investigators. In addition, the Core will provide consultation and assistance to investigators who may just be beginning to use molecular techniques and biomarkers in their research. The Nutrition Intervention Core, directed by Marci Campbell, Ph.D., will provide expertise and state-of-the-art resources and techniques for developing and evaluating nutritional interventions aimed at promoting health and preventing disease in populations at risk. CNRU investigators will have access to intervention development and tracking tools, and will receive help and consultation on their application to each project. Five junior investigators propose P/F projects on Selenium and arsenic toxicity, Gene targeted animal models for CVD, Church-based nutrition intervention in African Americans, Epidemiology of glucose intolerance during pregnancy, and Vitamin D therapy for bone disease in cystic fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIABETES MECHANISMS

IN

HEMOCHROMATOSIS:

PREVALENCE

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Principal Investigator & Institution: Mcclain, Donald A.; Professor and Director; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-OCT-2006 Summary: Although the hemochromatosis gene (HFE) has been identified there is little information about the diabetes that often accompanies the disease. We hypothesize nondiabetic homozygotes for mutations in HFE will exhibit a defect in insulin secretion as iron overload develops. This notion is supported by preliminary data obtained in HFE mutant mice. The insulin deficiency will progress to type 2 diabetes only if insulin resistance also occurs, either from cirrhosis or inheritance of type 2 diabetes genes.

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Insulin resistance from cirrhosis is hypothesized to result from excess carbohydrate delivery to peripheral tissues, resulting in excess hexosamine generation, an established cause of insulin resistance. Our specific aims are to: 1. Determine the prevalence of impaired glucose intolerance (IGT) and diabetes in clinically unselected individuals with hemochromatosis by oral glucose tolerance criteria. 2. Determine if a defect in insulin secretion exists in nondiabetic homozygotes with or without iron overload. This will be accomplished using the frequently sampled intravenous glucose tolerance test (FSIVGTT) with insulin levels. Reversibility of the defect will be examined after subjects have undergone phlebotomy. The hypothesis will be verified in studies of isolated islets from mice carrying disrupted or mutant HFE genes. 3. Using animal models, determine if diabetes in hemochromatosis results only when insulin resistance is superimposed on an iron- mediated defect in insulin secretion. 4. Determine the sequence and relative contributions of insulin resistance and hepatic glucose production (HGP) in the evolution of diabetes in human hemochromatosis. Insulin resistance and HGP will be quantified by the hyperinsulinemic euglycemic clamp and stable isotope techniques in subjects with hemochromatosis who have normal or IGT, with or without hepatic involvement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOES HYPERGLYCEMIA PREDICT PANCREATIC CANCER DIAGNOSIS? Principal Investigator & Institution: Chari, Suresh T.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Pancreatic cancer causes glucose intolerance and diabetes in up to 80% of patients. Pancreatic cancer induced diabetes (PaCDM) is often asymptomatic, of short duration (50 years of age may have PaCDM. We propose to establish whether newly elevated fasting blood glucose (FBG) is indicative of underlying pancreatic cancer as evidenced by diagnosis of pancreatic cancer within 3 years of the FBG measurement. If so, this would provide an entirely novel approach to screening for sporadic pancreatic cancer. We hypothesize that the 3-year likelihood of diagnosis of pancreatic cancer will be high in subjects: a) equal to or > 50 years of age with newly elevated FBG, b) with elevated fasting glucose who have known risk factors for pancreatic cancer (e.g. smoking), and/or c) who manifest an abrupt increase in FBG in serial measurements over time. We will identify visits to Mayo Clinic between years 1988 to 2002 by subjects equal to or >50 years of age who resided in its surrounding catchment area and had a routine physical examination that included a FBG. Preliminary data reveal that about 150,000 different subjects made >300,000 such visits during this time period providing >1 million person-years of follow-up. We will electronically retrieve clinical, and laboratory data and examine 3-year follow-up from date of FBG measurement to identify those diagnosed with pancreatic cancer. We expect 340 to 510 pancreatic cancer events in this cohort. Our Specific Aims are: Aim 1A). To test if FBG drawn during routine physical examination predicts likelihood of underlying pancreatic cancer and to test for non-linearity of this association. Aim 1B) To establish a FBG threshold that predicts a high 3-year likelihood of diagnosis of pancreatic cancer. Aim 2). To estimate the extent to which known risk factors for pancreatic cancer (age, smoking, obesity and family history) modify the likelihood of underlying pancreatic cancer in subjects with FBG greater than the threshold defined by Aim 1B. Aim 3). To test if patterns of change in serial measurements of FBG over time predict likelihood of underlying pancreatic cancer. The clinical and research implications of this study are

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considerable. These data may lead to delineation of individuals who have a high likelihood of existing pancreatic cancer, and who may be ideal candidates for more intensive screening or early detection regimens. The research described in this application is 100% relevant to pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF SLEEP APNEA ON METABOLIC FUNCTION Principal Investigator & Institution: Punjabi, Naresh M.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function. In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate: a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals. In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that: a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FASTING, INSULIN ACTION & POST-PRANDIAL METABOLISM Principal Investigator & Institution: Bergman, Bryan C.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-2002

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Summary: (Scanned from the applicant's description) Obesity is a public health epidemic that is commonly associated with insulin resistance, and predisposes people to development of Type II diabetes. I am interested in how insulin resistance affects nutrient metabolism, particularly in the post-prandial state, and the implications of this for obesity and diabetes. In the future, I intend to investigate effects of fasting and caloric restriction on post-prandial metabolism in lean, obese, and post-obese subjects. Acute changes in insulin action, despite having different origins to chronic insulin resistance, can profoundly affect nutrient metabolism. For example, two days of fasting induces glucose intolerance following a normal mixed meal, and promotes non-hepatic decreased insulin action. The proposed study will investigate the effects of an acute change in insulin action induced by fasting, on post-prandial nutrient partitioning in lean and obese men and women. The relative oxidation rates of meal- derived lipid and carbohydrate will be determined in addition to storage of meal derived nutrients. It is hypothesized that glucose intolerance induced by fasting will be associated with a) greater post-prandial lipid oxidation (endogenous and meal-derived), and b) greater storage of meal derived carbohydrate as glycogen. As these data have direct implications for weight reduction practices, studies will be performed in both lean and obese, men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE, INTRAUTERINE ENVIRONMENT AND PCOS Principal Investigator & Institution: Dunaif, Andrea E.; Chief, Division of Women's Health; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in premenopausal women. Women with PCOS have profound insulin resistance as well as pancreatic beta-cell dysfunction, independent of obesity and glucose intolerance. However, skeletal muscle insulin resistance reverse in cultured myotubes suggesting that insulin resistance in this tissue is induced by factors in the in vivo environment. We have recently shown that hyperandrogenemia is the reproductive phenotype in males as well as female relatives of PCOS women. Moreover, Urbanek and colleagues have shown (Project 2) that this phenotype appears to have a genetic basis in PCOS families and shows significant linkage and association with a marker locus on chromosome 19P in the region of the insulin receptor (allele 8 of D19S884). We now have extremely existing evidence that this allele is also associated with a metabolic phenotype in PCOS probands and their brothers: increased post-challenge glucose levels, apparent defects in insulin secretion, especially in response to sulfonylurea, and accelerated weight gain with age. Abbott (Project 3) has shown that in utero testosterone excess can reproduce many features of the PCOS reproductive and metabolic phenotype in female rhesus monkeys, including decreased insulin secretion and increased LH levels. Levine (Project 4) has shown that one mechanism for these changes is androgen-mediated sulfonylurea-stimulated insulin secretion by the pancreatic beta cells. Taken together, these observations have led to a new hypothesis for the etiology of PCOS: genetic variation resulting in hyperandrogenemia results in many of the reproductive and metabolic features of PCOS by fetal androgen programming. In this Project, we will test two components of the hypothesis. First, is the metabolic phenotype that is associated with the marker locus decreased insulin secretion, consistent with androgen-mediated suppression of K+/ATP channels? Second, is there in utero androgen excess, decreased fetal insulin secretion and/or intrauterine growth retardation (IUGR) in the female

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offspring of PCOS women, and does the marker allele identify a subpopulation of offspring with these findings? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUCOSE TOLERANCE IN HIV INFECTED PATIENTS ON PROTEASE INHIBITOR THER Principal Investigator & Institution: Erbelding, Emily J.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The pathogenesis of glucose intolerance in patients taking PI therapy and developing diabetes is not known. The oral glucose tolerance test has been used clinically to screen for diabetes mellitus. We propose to use the oral glucose tolerance test to address the specific aims outlined below: 1. To determine if use of protease inhibitors is associated with glucose intolerance. 2. To determine if acute phase insulin release is appropriate in patients on protease inhibitors. The patient population for this study will be adult men and women with HIV infection, with no prior history of diabetes who are about to initiate antiretroviral therapy using one or more protease inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUCOSE TRANSPORTER REGULATION IN OBESITY AND DIABETES Principal Investigator & Institution: Kahn, Barbara B.; Chief; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2006 Summary: Recent studies challenge long-held paradigms about the role of specific insulin target tissues in whole body insulin action and in the pathogenesis of insulin resistance. Studies in this application will investigate the importance of the Glut4 glucose transporter in muscle and adipose tissue, and the dynamic interactions by which altering glucose transport in one of these tissues may cause insulin resistance in other insulin target tissues including liver. The overall goal is to determine the role of glucose transport in adipose tissue and in muscle in whole body glucose homeostasis. Our preliminary data indicate that markedly reducing Glut4 expression selectively in adipose tissue causes insulin resistance and glucose intolerance which are as severe as knocking out Glut4 from muscle. This is important since in humans with obesity and type 2 diabetes, Glut4 expression is down-regulated in adipocytes but not in skeletal muscle. We also find that mice with muscle specific Glut4 knockout eventually become insulin resistant in fat and liver. We will investigate the molecular mechanisms for these effects. Specific aims are: 1) To determine the mechanisms by which altering Glut4 expression selectively in adipocytes affects whole body glucose homeostasis. 2) To determine what genes/molecules mediate the effects of altered Glut4 expression in adipocytes on whole body glucose homeostasis. 3) To determine the role of brown adipose tissue in the insulin resistance caused by reduced Glut4 expression is adipose tissue. 4) To determine the mechanisms by which altering Glut4 expression selectively in muscle affects insulin action in other tissues. 5) To determine whether combined knockout of Glut4 from adipose tissue and muscle will lead to greater insulin resistance than knockout from either tissue alone and how this is affected by genetic background. These studies will lead to a better understanding of the mechanisms for regulation of glucose homeostasis and the role of impaired glucose transport, which is present in

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adipocytes and muscle of humans with obesity and type 2 diabetes, in the pathogenesis of insulin resistance. Our goal is to find new therapeutic targets to prevent or ameliorate type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAPO: DATA COORDINATING CENTER Principal Investigator & Institution: Dyer, Alan R.; Professor and Associate Chair; Preventive Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 04-MAY-1999; Project End 31-MAR-2004 Summary: There is a consensus that overt diabetes mellitus (DM), whether or not accompanied by symptoms or signs of metabolic decompensation, is associated with a significant risk of adverse pregnancy outcome. On the other hand, the risk of adverse outcome associated with degrees of glucose intolerance less severe than overt DM is controversial. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a basic epidemiologic investigation aiming to clarify unanswered questions on the association of various levels of glucose intolerance during the third trimester of pregnancy and risk of adverse outcomes. Its General Aim -- by means of an international cooperative study involving 16 centers and approximately 25,000 pregnant women -- is to achieve a major advance in knowledge on levels of glucose during pregnancy that place the mother, fetus, and neonate at increased risk. The primary hypothesis is that hyperglycemia during pregnancy, less severe than overt DM, is associated with increased risk of adverse maternal, fetal, and neonatal outcome that is independently related to the degree of metabolic disturbance. Specific Aims of HAPO are: 1. to examine glucose tolerance in a large, heterogeneous, multinational, multicultural, ethnically diverse cohort of women in the third trimester of gestation with medical caregivers "blinded" to status of glucose tolerance (except in those instances where fasting and/or two hour OGTT plasma glucose concentration exceeds a predefined cutoff value); and 2. to derive internationally acceptable criteria for the diagnosis and classification of gestational diabetes mellitus (GDM) based on the specific relationships between maternal glycemia and the risk of specific adverse outcomes that are established through this study. The study is to be accomplished with high quality standardized data collection on the women during the third trimester of gestation (including the OGTT) and at time of delivery for assessment of adverse outcomes, including operative delivery (caesarean section), increased fetal size (macrosomia/obesity), neonatal morbidity (hypoglycemia), and fetal hyperinsulinism. HAPO is to include a Clinical Coordinating Center and Data Coordinating Center, both located at the Northwestern University Medical School in Chicago, as well as a Central Laboratory located in Belfast, United Kingdom. This application requests support for the Data Coordinating Center for HAPO. Cost effectiveness for HAPO is enhanced through cost sharing by colleagues in non-U.S. centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV PROTEASE INHIBITORS AND GLUCOSE TRANSPORT Principal Investigator & Institution: Mueckler, Michael M.; Professor; Cell Biology and Physiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-JAN-2002; Project End 31-DEC-2004 Summary: (Provided by the applicant): The advent of HIV protease inhibitor (PI) therapy was a major advance in the treatment of HIV infection. Combined treatment of

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HIV-infected patients with reverse transcriptase inhibitors and PIs (intensive antiretroviral therapy, IART) has been shown to delay the onset of overt disease and to prolong survival. Current guidelines recommend the use of IART for the treatment of all newly diagnosed cases of HIV infection. Unfortunately, IART is associated with the development of numerous metabolic abnormalities, including peripheral lypodystrophy, hyperlipemia, insulin resistance, glucose intolerance, and type 2 diabetes. The reported incidence of type 2 diabetes in PI-treated patients is at least 10fold greater than that in the general age- and sex-matched population and is particularly alarming considering the relatively young age of the patient populations and the rapidity of diabetes onset after the start of therapy. PIs have recently been shown to rapidly and selectively suppress the activity of Glut4, the insulin-responsive glucose transporter, an effect that can directly account for the insulin resistance and increased incidence of diabetes associated with PI therapy. The long-term goal of this proposal is to elucidate the relationship between the effect of PIs on Glut4 and the metabolic abnormalities associated with IART and to determine the mechanism of the effect of PIs on Glut4 activity. To accomplish these goals, the following specific aims will be pursued: 1) To determine the acute effect of PIs on whole body glucose disposal and glucose transport in skeletal muscle. This aim will directly test the hypothesis that Pls acutely induce whole-body insulin resistance via the inhibition of skeletal muscle Glut4. 2) To determine whether PIs suppress insulin-stimulated glucose transport by direct binding to Glut4. This aim will ascertain whether the PI effect is due to competitive or noncompetitive binding to Glut4 or binding to a molecule involved in the regulation of Glut4 activity in the plasma membrane. 3) To determine whether PIs suppress the activity of Glut isoforms other than Glut4. This aim will address a potentially important clinical issue: whether PIs, as a result of the inhibition of one or more of the other 8 known Glut isoforms, may have iatrogenic effects that have not yet been detected. 4) To determine the structural determinants of Glut4 interaction with PIs. This aim will identify specific Glut4 domains and amino acid residues involved in its predicted binding to PIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERGLYCEMIA AND ADVERSE PREGNANCY OUTCOME Principal Investigator & Institution: Metzger, Boyd E.; Professor; Medicine; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 04-MAY-1999; Project End 31-MAR-2004 Summary: There is a consensus that overt diabetes mellitus (DM), whether or not accompanied by symptoms or signs of metabolic decompensation, is associated with a significant risk of adverse pregnancy outcome. On the other hand, the risk of adverse outcome associated with degrees of glucose intolerance less severe than overt DM is controversial. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a basic epidemiologic investigation aiming to clarify unanswered questions on the association of various levels of glucose intolerance during the third trimester of pregnancy and risk of adverse outcomes. Its General Aim, by means of an international cooperative study involving 16 field centers and approximately 25,000 pregnant women, is to achieve a major advance in knowledge on levels of glucose during pregnancy that place the mother, fetus, and neonate at increased risk. The primary hypothesis is that hyperglycemia, less severe than overt DM, is associated with increased risk of adverse maternal, fetal, and neonatal outcome that is independently related to the degree of metabolic disturbance. Specific Aims of HAPO are: 1. To examine glucose tolerance in a large, heterogeneous, multinational, multicultural, ethnically diverse cohort of women

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Glucose Intolerance

in the third trimester of gestation with medical caregivers "blinded" to status of glucose tolerance (except in those instances where fasting and/or two hour OGTT plasma glucose concentration exceeds a predefined cutoff value); and 2. To provide data that can be used to derive internationally acceptable criteria for the diagnosis and classification of gestational diabetes mellitus (GDM) based on the identification of pregnancies at risk for specific adverse outcomes. The study is to be accomplished with high quality standardized data collection on the women during the third trimester of gestation (including the OGTT) and at time of delivery for assessment of adverse outcomes, including fetal hyperinsulinism, fetal obesity (macrosomia), operative delivery (caesarian section), and neonatal morbidity (hypoglycemia). HAPO is to include field centers and regional centers where the participants will be studied, a Clinical Coordinating Center and Data Coordinating Center, both located at the Northwestern University Medical School in Chicago, as well as a Central Laboratory located in Belfast, Northern Ireland. This application requests support for the Clinical Coordinating Center, the field and regional centers and Central Laboratory. Cost effectiveness for the HAPO study is enhanced through cost sharing by colleagues in non-U.S. centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN & GLUCOSE SIGNALING PATHWAYS IN ISLET BETA CELLS Principal Investigator & Institution: Kulkarni, Rohit N.; Assistant Professor; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Type 2 diabetes is characterized by insulin resistance and beta-cell failure resulting in uncontrolled hyperglycemia. The basis of the beta-cell defect is presently unclear. A growing body of evidence indicates insulinsignaling proteins are present in the islets and contribute to the maintenance of glucose homeostasis. Thus, normal beta-cells show glucose-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1). Secondly, mice with a targeted disruption of the IR show loss of insulin secretory response to glucose and progressive glucose intolerance. Third, primary islets and beta-cell lines derived from IRS-1 knockout mice show reduced insulin content and blunted secretory responses to multiple stimuli, and IRS-2 knockout mice manifest a defect in beta-cell development. These data indicate the presence of an insulin-signaling pathway in the islets/beta-cells potentially linked to glucose signaling that plays an important role in islet function. The goals of this proposal are to understand the mechanisms by which the insulin-signaling proteins modulate beta-cell function and to delineate the cross-talk between the insulinand glucose-signaling pathways. Our studies will be directed at the following specific aims: 1) to identify the cellular mechanisms by which proteins in the insulin-signaling pathway modulate insulin secretion and synthesis in response to different stimuli, 2) to determine the alterations in glucose metabolism in islets/beta-cells isolated from mice lacking the IR and the IRS proteins and to study the effects of re-expression of the proteins in the knockout cell lines, and 3) to evaluate the expression of insulin signaling proteins and glucose metabolism in islets isolated from rodent models of diabetes. My earlier training in islet physiology and metabolism and the experience I am currently gaining as a research fellow at the Joslin Diabetes Center have provided me with a unique perspective to explore the significance of the insulin signaling pathway in islet/beta-cell function. The mentoring support of Prof. Kahn and the academic environment of the Joslin Diabetes Center and Harvard Medical School provides me

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with an excellent opportunity to continue my investigation in type 2 diabetes and further develop my skills to attain my goals as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN ACTION IN MUSCLE & FAT CELL Principal Investigator & Institution: Lawrence, John C.; Professor; Pharmacology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-1981; Project End 31-MAR-2006 Summary: Insulin lowers blood glucose by stimulating glucose uptake and storage in various target tissues, the most important being liver, skeletal muscle, and fat. The failure to respond appropriately to insulin results in a rise in blood sugar. Type II diabetes mellitus develops if beta cells become unable to release enough insulin to compensate for the insulin resistance. Determining the processes involved in the normal response to insulin will be essential for understanding insulin resistance, and the overall objective of this project is to define mechanisms involved in the actions of insulin in skeletal muscle and fat cells. Initial aims are to investigate the stimulation of glycogen synthesis by insulin. This effect is of particular importance in the control of blood glucose levels, as most of the glucose taken up following a meal is deposited as glycogen in skeletal muscle. Experiments in Aim 1 are proposed to investigate both the mechanism through which insulin activates glycogen synthase (GS), the enzyme that synthesizes glycogen from uridine diphosphoglucose (UDPG), and the importance of increasing GS activity in the stimulation of glycogen synthesis. Treating rats with insulin results in a marked decrease in muscle UDPG, implying that the activity of UDPG pyrophosphorylase (PPL) may limit the rate of glycogen synthesis. Objectives of Aim 2 are to determine whether UDPG PPL is subject to hormonal and/or metabolic control, and to investigate the potential limiting role of UDPG PPL in glycogen synthesis in rodent and human muscles. In the last two Aims we will investigate new targets of insulin action. We have recently discovered an adipocyte protein, designated betaip140, which is phosphorylated in response to insulin and coimmunoprecipitates with the beta isoform of protein kinase B (PKB). By purifying betaip140 and sequencing peptides by tandem mass spectrometry, we have shown that betaip140 is the product of the Kiaa0188 gene, recently identified by genetic fine mapping as a candidate gene for the fld mouse phenotype. Mice homozygous for the fld gene exhibit insulin resistance, glucose intolerance, and markedly diminished adipose tissue mass. Aim 3 is to investigate the potential interactions between betaip140 and PKBbeta, to define the mechanisms controlling betaip140 phosphorylation, and to determine the role of betaip140 in insulin action. Many other proteins that are phosphorylated in response to insulin can be detected, but have not been identified. This represents a serious gap in our understanding of insulin action, since at least some of the proteins are likely to represent downstream targets that are involved in the important metabolic responses to insulin. The objective of Aim 4 is to identify these new targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INSULIN AND THE POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Nestler, John E.; Professor and Chairman; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2005 Summary: The polysystic ovary syndrome (PCOS) is a poorly understood disorder that affects approximately 6-10 percent of women of reproductive age. PCOS is characterized

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Glucose Intolerance

by hyperandrogenism and chronic anovulation, and is the leading cause of female infertility in the United States. Women with PCOS are also at high risk for developing type 2 diabetes, presumably due to the insulin resistance that accompanies the syndrome. Our long-term goal is to elucidate the relationship between insulin resistance and PCOS, especially as it relates to hyperandrogenism. Some actions of insulin may be effected by putative inositolphosphoglycan (IPG) mediators of insulin action and a deficiency in a specific D-chiro-inositol-containing IPG may contribute to insulin resistance in individuals with impaired glucose tolerance or type 2 diabetes. Our studies indicate that D-chiro-inositol (DCI) administration improves glucose intolerance while reducing circulating insulin in women with PCOS, and is also associated with decreases in serum androgens and improved ovulatory function. In addition, our in vitro studies in human thecal cell cultures suggest that the IPG signaling system plays a role in transducing insulin's stimulation of ovarian androgen biosynthesis. These studies have led us to focus our short- term goals on an assessment of the role of the IPG signaling system in PCOS, and pursue a unifying hypothesis to explain the above experimental observations. Our hypothesis is that women with PCOS are DCI deficient, perhaps related to an intracellular defect in the conversion of myo-inositol (MYO) to DCI. This results in a decrease in a DCI-containing IPG mediator (DCI-IPG) and an increase in a MYO-containing IPG mediator (MYO-IPG) bound to the outer leaflet of the cell membrane. We further propose that the resulting deficient insulin-mediated release of DCI-IPG contributes to insulin resistance in PCOS, whereas the simultaneous hyperinsulinemia mediated increased release of MYO-IPG at the level of the ovary acts to stimulate ovarian androgen biosynthesis. If our proposed studies confirm a role for IPG's in insulin resistance and hyperandrogenism of PCOS, they will substantially enhance our understanding of the disorder's pathogenesis and are likely to provide insights into novel treatment strategies directed specifically at the IPG system and normalization of its function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN MEDIATED GLUCOSE TRANSPORT DISRUPT BY ETHANOL Principal Investigator & Institution: Nagy, Laura E.; Associate Professor; Nutrition; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from the investigator's abstract). Epidemiological studies have identified alcohol consumption as an independent risk factor for the development of non-insulin dependent diabetes mellitus (NIDDM). Moreover, both short and long-term ethanol consumption result in glucose intolerance in humans and rats. However, the mechanism(s) for this disruption of glucose homeostasis by ethanol is not well understood. Since adipose and skeletal muscle are major sites for both insulin action and glucose disposal, the applicants have investigated the effects of ethanol on insulinmediated control of glucose transport in adipocytes and skeletal muscle from rats. Ethanol feeding to rats for four weeks decreased insulin-stimulated glucose uptake in adipocytes and soleus, a red oxidative muscle, but had no effect on uptake in the epitrochlearis, a white glycolytic muscle. Decreased uptake in the adipocyte was associated with an impairment in translocation of GLUT4 from intracellular vesicles to the plasma membrane. Total GLUT4 protein was also reduced after ethanol feeding; as in other model systems, decreased GLUT4 was associated with an increase in G alpha s and cAMP production in the adipocyte. The major goals of this proposal will be to determine whether ethanol impairs insulin-stimulated glucose uptake in red, oxidative

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muscle and adipocytes by: (1) disrupting insulin receptor mediated signal transduction and/or (2) impairing the ability of GLUT4 vesicles to dock and fuse with the plasma membrane. The effects of ethanol on early events in insulin signalling (insulin receptor substrate-1 phosphorylation and activation of phosphotidylinositol-3-kinase) which lead to translocation of GLUT4 will be measured. The applicants will also investigate the effects of ethanol on the intracellular distribution of GLUT4 protein after insulin stimulation, as well as the distribution of vesicular proteins involved in GLUT4 vesicle trafficking. Investigation of the mechanisms for ethanol-induced insulin resistance is critical for understanding the interaction between alcohol consumption and the development of NIDDM. Such an understanding will foster the development of strategies to either prevent or reverse the long-term effects of ethanol on glucose homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: JAPANESE AMERICAN COMMUNITY DIABETES STUDY Principal Investigator & Institution: Boyko, Edward J.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This longitudinal study examines the relationship of environmental factors in the development of the insulin resistance syndrome (hyperinsulinemia, central obesity, glucose intolerance, hypertension, dyslipidemia, and coronary heart disease) in Japanese Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KETONE DYSREGULATION AND MUSCLE INSULIN RESISTANCE Principal Investigator & Institution: Muoio, Deborah M.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): Compelling evidence links the development of muscle insulin resistance to fatty acid (FA) oversupply, but there is still uncertainty regarding which specific FA metabolite(s) and regulatory pathways are directly responsible for mediating insulin desensitization. Our current knowledge is based largely on a candidate molecule approach in which the selection of potentially relevant lipid metabolites relies heavily on implicit biases or availability of specific assays. To overcome this obstacle, we have employed mass spectroscopy-based metabolic profiling to comprehensively evaluate multiple lipid-derived metabolites in muscle from rats made insulin resistant by a high fat diet compared to controls. This unbiased "metabolomics" approach led to our discoveries that insulin resistant rats exhibit marked intramuscular accumulation of the ketone, beta-hydroxybutyrate (betaHB), at least a portion of this accumulated ketone was synthesized directly in the muscle tissue, and that genetic manipulations that restored insulin sensitivity corresponded with a 55% decrease in muscle (HB levels. These exciting findings implicate muscle ketone dysregulation as a causal factor in the etiology of lipid-induced insulin resistance. Previous research supports an inverse correlation between ketogenesis and glucose intolerance, but no consideration has been given to the possibility that dysregulated metabolism of ketones within muscle tissue could contribute to insulin resistant states. We hypothesize that chronic high fat feeding and/or overnutrition imposes a state of persistent and abnormal ketogenesis in skeletal muscle, which in turn plays a direct role in causing maladaptive changes in glucose handling and insulin sensitivity. We propose

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to test these hypotheses with the following specific aims: 1) To determine whether ketone dysregulation is a common feature in multiple animal models of insulin resistance. This will be done by profiling gene expression and metabolic markers of ketone metabolism in rodent models of obesity and diabetes. 2) To determine whether perturbing ketone metabolism (by FA overexposure or by adenovirus-mediated delivery of ketogenic genes), disrupts glucose handling and insulin signaling in isolated muscles and/or muscle cells in culture. 3) To determine whether adenovirus-mediated overexpression of genes that suppress ketogenesis and/or enhance ketone degradation in muscle can reverse diet-induced insulin resistance in vivo. The results from these studies are expected to yield important new insights into the mechanism of FA-induced insulin resistance in skeletal muscle, with potential therapeutic implications for treatment of type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEPTIN AND PERIPHERAL GLUCOSE METABOLISM Principal Investigator & Institution: Harris, Ruth B.; Associate Professor; Foods and Nutrition; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 28-FEB-2004 Summary: Leptin is a protein produced by adipose tissue and hypothesized to be a circulating lipostatic factor (82). Our preliminary data shows that leptin infusion into normal mice inhibits insulin release in response to a glucose challenge, induces insulin resistance in adipocytes, but promotes insulin-stimulated glycogen synthesis in muscle. An impaired acute insulin release in response to glucose is a risk factor for development of non-insulin dependent diabetes (NIDDM) (25) and increased insulin-stimulated glycogen synthesis in muscle is characteristic of the early metabolic changes observed during the development of insulin resistance in high-fat fed rats (48). We hypothesize that leptin mediates development of an impaired glucose tolerance that precedes early NIDDM by suppressing glucose stimulated insulin release and modifying insulinstimulated glucose utilization in a tissue and pathway specific manner. Experiments described in Specific Aim 1 will examine the effects of leptin infusion on glucose and fatty acid metabolism of the three major insulin-responsive tissues in lean mice and will determine whether the effects on insulin responsiveness are mediated by the long-form leptin receptor, OB-Rb. Experiments in Specific Aim 2 will investigate the role of leptin in modifying insulin signaling to determine whether leptin changes tissue insulin receptor number, glucose transporter number or translocation, and insulin receptor tyrosine kinase activity. These processes represent the first stage of the insulin signaling cascade and the results of these experiments will determine how leptin modifies the initial stages of insulin signaling to change peripheral tissue glucose utilization. The studies described in this proposal will provide the information required to understand how leptin treatment modifies insulin responsiveness in peripheral tissues and the mechanisms by which this is achieved. It is essential to elucidate this aspect of leptin activity as it may account for the increased risk of development of glucose intolerance that is associated with obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIPODYSTROPHY AMONG HIV-INFECTED PATIENTS Principal Investigator & Institution: Crane, Heidi M.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 30-APR-2009

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Summary: (provided by applicant): CANDIDATE: Heidi M Crane, MD, MPH is currently completing an Infectious Disease Fellowship at the University of Washington. Her long-term interest in complications of HIV disease has developed into a specific interest in the epidemiology of metabolic complications among HIV-infected patients. ENVIRONMENT: The University of Washington represents an ideal environment for Dr Crane's training and for the research she proposes. World-renowned clinical and epidemiological expertise related to HIV and to metabolism are available to support the development of Dr. Crane's research career. RESEARCH: A dramatic decline in overall HIV-related morbidity and mortality has been accompanied by an increase in metabolic complications such as lipodystrophy. The syndrome of lipodystrophy consists of several body morphology abnormalities and is often associated with metabolic abnormalities such as dyslipidemia and glucose intolerance. Why some patients develop these complications and others do not is not understood. Dr. Crane proposes to study body morphology and metabolic abnormalities in a clinical cohort of approximately 1500 patients infected with HIV. This investigation will be facilitated by the University of Washington HIV Information System, a state-of-the art clinical and research database, and by the longitudinal collection of patient-completed measures of body morphology abnormalities, depression, and health-related quality-of-life. This study will examine the association between antiretroviral therapy, patient-related characteristics, and the development of body morphology and metabolic abnormalities. This study will also examine the association between body morphology abnormalities and health-related quality-of-life. Identification of factors that increase or decrease the likelihood of developing metabolic abnormalities may lead to changes in the clinical care of patients with HIV; to advances in understanding the mechanisms that lead to the development of these abnormalities; and ultimately to therapy for these complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG-TERM FOLLOW-UP OF A PROSPECTIVE RANDOMIZED TRIAL OF SIROLIMUS AND TACROLIMUS Principal Investigator & Institution: Matas, Arthur J.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Our objectives are to determine the best long-term immunosuppression protocol for kidney transplant recipients on a steroid-free regimen. Steroids are associated with numerous side effects posttransplant including osteoporosis, avascular necrosis, fractures, cataracts, hypertension, glucose intolerance, and appearance and mood changes. And it is recognized that side effects lead to noncompliance; in transplantation, noncompliance reads to increased rejection and graft loss. We and others have shown that kidney transplants can be successfully done with either complete avoidance or rapid discontinuation of steroids. We will compare long-term outcome of 3 immunosuppressive protocols, all using antibody induction and rapid discontinuation of prednisone: cyclosporine and mycophenolate vs. high (blood) level tacrolimus and low level sirolimus vs. low (blood) level tacrolimus and high level sirolimus. Our main end points will include patient and graft survival, incidence of biopsy-proven chronic allograft nephropathy, and renal function. We will also determine the incidence of complications and the long-term costs of the individual protocols. We will be able to determine whether or not one of these clinical care protocols provides better outcome for kidney transplant recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM OF GLUCOSE INTOLERANCE PREADOLESCENT/ADOLESCENT CHILDREN WITH IDDM

IN

Principal Investigator & Institution: Tamborlane, William V.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ACTION IN DPP INTERVENTIONS Principal Investigator & Institution: Kitabchi, Abbas E.; Professor; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 05-AUG-1998; Project End 30-JUN-2005 Summary: (adapted from the application) The Diabetes Prevention Program (DPP) is an NIH-sponsored multicenter study with the specific objective of comparing, in high risk individuals, the efficacy of three intervention methods (intensive behavior modification, metformin, and troglitazone) vs control placebo group in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). A total of 4000 subjects (from 26 clinical centers) of whom 50% will consist of minority groups, will be randomly assigned to one of the four groups. Since the DPP is not designed to study the mechanism of action of these interventions, the present proposal is an ancillary study to the DPP to investigate the mechanisms by which the three interventions affect glucose intolerance and insulin resistance. Other rationales for the proposed study are that: (a) hyperandrogenism and decreased sex hormone binding globulin (SHBG) are known to be additional risk factors for development of NIDDM in certain female populations, (b) hyperandrogenism of gonadal origin [i.e. testosterone(T), and androstenedione(A)] is believed to be more deleterious to glucose tolerance and insulin sensitivity than adrenal androgens [i.e. DHEA(D) DHEAS(DS)] and c) recent preliminary studies suggest that metformin, troglitazone and exercise plus dietary modification alter androgenic profiles and improve glucose intolerance, possibly by three different mechanisms. Therefore, the DPP offers a unique opportunity to study the mechanism of action of these three interventions. We hypothesize that those modalities which most improve glucose intolerance and insulin resistance will be associated with more favorable androgenic profiles (i.e. lower T/D ratio) and CV risk factors. The specific aim of this ancillary study is to recruit 200 pre- and perimenospausal women from eight of the DPP centers (equally distributed among the four treatment groups) and among three ethnic groups (Caucasians, Hispanics and African-Americans) to: (a) assess insulin secretion by OGTT, (b) measure androgenic profiles, (c) measure body fat distribution by CT Scan, and lean body mass (LBM) and fat content by DEXA and (d) study glucose and insulin metabolism and clearance, and insulin sensitivity by the use of modified frequently sampled iv glucose tolerance test (FSIGT). These studies will be done at baseline, and at the end of the 1st and 3rd year of intervention. The proposed ancillary study should, therefore, enable us to assess the correlation between glucose intolerance, insulin resistance, and androgenic profile, as well as the effect of various treatment modalities on them and the mechanism of action, in a setting of multiethnic diabetes prevention program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF INSULIN RESISTANCE IN GDM Principal Investigator & Institution: Friedman, Jacob E.; Associate Professor of Pediatrics; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Gestational Diabetes Mellitus (GDM) complicates up to 10% of all pregnancies and results in fetal hyperinsulinemia, macrosomia, and maternal complications during delivery. The morbidity to the mother and fetus does not end after pregnancy as recent data demonstrate a higher risk of obesity and glucose intolerance in adult offspring from GDM women and extremely high risk for type II DM in former GDM women. Our human studies have shown that a major defect in GDM involves the inability of insulin to stimulate glucose transport into skeletal muscle. The mechanisms for this severe insulin resistance are unknown, but likely involve a defect in the insulin receptor, IRS-1, and an unknown post-receptor defect at the level of GLUT4 translocation. The long-term goal of this project is to elucidate the underlying molecular signaling mechanisms that provoke insulin resistance in women with GDM. In this proposal we will dissect the roles of hormones of pregnancy, including TNFalpha, as negative regulators of insulin signaling, with a special emphasis on mechanisms for serine phosphorylation of IR and IRS-1 using human muscle fibers and L6 myotubes. Specific Aim 1 will test the hypothesis that re-distribution of PI 3-kinase to the insulin receptor mediates insulin resistance in pregnancy by triggering increased serine kinase activity to inhibit IRtyrosine phosphorylation and trigger IRS-1 degradation. In Specific Aim 2, we will determine how placental derived hormone(s) down-regulate IR and IRS-1 signaling using L6 muscle cells. In Specific Aim 3, we will investigate the contribution of skeletal muscle TNFalpha production as a mechanism for greater insulin resistance in women with GDM. In Specific Aim 4, we will explore the role of the novel CAP/Cbl signaling pathway as a potential mediator of GLUT4 translocation independent of PI 3-kinase. The outcome of these studies will provide important new insights into how pregnancy triggers insulin resistance in human skeletal muscle, and novel mechanisms for the down-regulation of insulin signaling. Ultimately, these studies should provide us with a better understanding of the cellular factors that trigger human GDM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF THE GLUCOSE INTOLERANCE OF AGING Principal Investigator & Institution: Ader, Marilyn; Associate Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 02-DEC-1998; Project End 30-NOV-2002 Summary: Impaired glucose tolerance is a hallmark of aging even in the absence of attendant pathology, and is associated with increased mortality due to enhanced risk for development of diabetes and cardiovascular disease. Intolerance of aging is typically attributed to the development of insulin resistance, resulting from changes in adiposity, diet, and/or sedentary lifestyle, and studies to understand the pathogenesis of intolerance have focused on the relative contributions of insulin resistance and pancreatic islet dysfunction. We have demonstrated that insulin-independent mechanisms of glucose regulation are equally important in determining glucose tolerance. These processes, termed "glucose effectiveness", are defined as the actions of glucose to regulate its own utilization (Rd) and hepatic production (HGO) independent

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of elevated insulin. The purpose of this proposal is to examine the role of glucose effectiveness in the glucose intolerance of normal, non-diseased aging in the rat. We will test the hypothesis that in insulin-resistant states such as aging, efficient disposition of a carbohydrate challenge becomes increasingly dependent on metabolic factors which are independent of insulin action, i.e. glucose effectiveness. These studies will establish the role of glucose effectiveness in the glucose intolerance of normal, non-diseased aging. We will apply newly developed methods to quantify glucose effectiveness directly in young and old rats, and determine how aging alters the relative contributions of Rd vs HGO and the specific tissue sites and glucose transporters involved. We will examine the mechanisms by which glucose effectiveness may compensate in agingassociated insulin resistance. Finally, we propose to examine the ability of caloric restriction to improve tolerance through their actions on glucose effectiveness, and determine the tissue sites, mechanisms, and glucose transporters which may be involved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT-0RIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Gater, David R.; Assistant Professor; Phys Med and Rehabilitation; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): SCI predispose to glucose intolerance and insulin resistance, presumably due to changes in body composition and skeletal muscle dysfunction, placing SCI individuals at greater risk for diabetes and coronary artery disease. In the able-bodied, marked improvements in glucose tolerance have been reported in response to aerobic exercise, with variable changes in insulin sensitivity. Resistance training has also improved glucose tolerance, and to a greater extent, insulin sensitivity in the able-bodied. Exercise responses in SCI have not been examined as extensively as they have in the general population, and yet this population has significantly more to gain than the able-bodied population by improving metabolic and functional abilities. The proposed hypothesis is that aerobic exercise, resistance training and/or a combination of aerobic exercise and resistance training will improve body composition and glucose tolerance, but only exercise which involves resistance training, and subsequent increases in muscle mass, will significantly improve insulin sensitivity in individuals with SCI. Twenty individuals with motor complete T6-L2 SCI will be recruited each year to participate in one of the following exercise protocols. Subjects will be randomly assigned to control or aerobic (Trial 1), resistance (Trial 2), and combined (Trial 3) exercise groups. Glucose tolerance, insulin sensitivity and body fat will be determined before and after each of the exercise interventions. If glucose intolerance and subsequently diabetes mellitus can be prevented in individuals with SCI by utilizing appropriately dosed exercise, significant savings in health care dollars and improved quality of life could be realized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MELATONIN

METABOLIC

CHANGES

DURING

AGING:

A

ROLE

FOR

Principal Investigator & Institution: Rasmussen, Dennis D.; Research Associate Professor; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105

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Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant) Adiposity, especially intra-abdominal adiposity, commonly increases by middle age in humans, non-human primates and rats, as do plasma insulin and leptin. These aging-associated increases in adiposity, insulin and leptin levels are associated with detrimental metabolic consequences, such as glucose intolerance, insulin resistance, diabetes, dyslipidemia, hypertension and cardiovascular disease. This spectrum of disorders, commonly grouped together as the "metabolic syndrome," is responsible for considerable aging-associated progressive pathology. Conversely, nocturnal pineal melatonin secretion decreases with aging in humans, other primates and rats. The proposed investigation evolves from our ongoing work demonstrating that chronic daily nocturnal administration of melatonin to middle-aged and older rats to produce youthful plasma melatonin levels and restore full amplitude circadian rhythmicity of plasma melatonin exposure also restored intra-abdominal adiposity, plasma insulin and plasma leptin to youthful levels. Administration of melatonin to young rats did not alter any of these parameters, suggesting that these responses were dependent upon the aging-associated decline in endogenous melatonin secretion. If melatonin supplementation to primates exerts these same effects, appropriate melatonin treatment could potentially provide effective prophylaxis or therapy for significant progressive pathologies associated with aging. Although indirect evidence suggests that melatonin may indeed play a role in regulating metabolism, body weight and adiposity in primates, a cause-effect relationship remains to be demonstrated. Testing this hypothesized relationship in middle-aged rhesus monkeys is the sole specific aim of the proposed investigation. A single study will be conducted, utilizing daily nocturnal intravenous melatonin vs. control infusions in unanesthetized and freely-moving middle-aged rhesus monkeys bearing indwelling vascular catheters protected by tethers. If chronic daily nocturnal melatonin treatment does decrease the monkeys' body weight, abdominal adiposity, plasma insulin, and/or insulin sensitivity to more youthful levels, the results of this investigation will justify and facilitate subsequent investigations to resolve mechanisms and clinical utility of these responses. Development of a therapy or preventive treatment that would attenuate or reverse the detrimental changes in carbohydrate and lipid metabolism which are commonly first expressed at middle age would reduce the progressive aging-associated morbidity which is the consequence of these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC SYNDROME IN ADULT SURVIVORS OF CHILDHOOD ALL Principal Investigator & Institution: Gurney, James G.; Associate Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 15-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Treatment for acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, involves 24 to 36 months of chemotherapy and high dose steroids. Additionally, cranial radiation is sometimes included for treatment or prevention of central nervous system involvement. The 5-year survival probability of childhood is all over 80%, and there are tens of thousands of adult survivors worldwide. These individuals have a higher than expected frequency of obesity and early mortality from cardiovascular disease. Childhood ALL survivors may also be at increased risk for the metabolic syndrome, a constellation of disorders characterized by central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. The syndrome is clearly associated with substantially elevated risks

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for type 2 diabetes mellitus and atherosclerotic coronary disease. Deficiency in growth hormone secretion, which can result from damage to the hypothalamic-pituitary axis from either chemotherapy or cranial radiation, has been implicated in the pathogenesis of metabolic syndrome in childhood cancer survivors. 75 adult survivors of childhood ALL, ages 18-49 years will be randomly selected and recruited from an ongoing epidemiologic study to participate in a 2-day clinical evaluation. The aims of this study are to: 1) compare the extent to which prevalence of the metabolic syndrome is higher in ALL survivors than in same age, same sex population norms; 2) evaluate the relation between growth hormone deficiency and the metabolic syndrome; 3) investigate whether endothelial impairment and other early signs of cardiovascular disease are more prevalent among ALL survivors with, versus without, the metabolic syndrome; and 4) compare whether adjuvant cranial radiation increases risk for the metabolic syndrome above that of chemotherapy alone. A comparative evaluation of health behaviors and health knowledge related to diabetes, cardiovascular disease, physical activity, and nutrition, and will also be included in the study. This proposal addresses the great need for clinical research on long-term, adverse effects of childhood cancer and its treatment, particularly those that are preventable or modifiable. The study will provide important data on potential etiologic factors, such as growth hormone deficiency and cranial radiation, and on potential avenues for education and intervention, such as targeted modifications of physical activity and dietary habits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS Principal Investigator & Institution: Carpenter, Marshall W.; Director, Maternal Fetal Medicine, Assoc; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, Ri 029052499 Timing: Fiscal Year 2002; Project Start 03-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): WIH and the Department of Obstetrics and Gynecology at Brown University School of Medicine have the capability to participate actively as a new member of the Cooperative Multicenter Maternal-Fetal Medicine Units Network. WIH operates one of the nation?s larger obstetrical services. All obstetric care is supported by insurance in Rhode Island. Consequently, the State?s ethnic and racial diversity is reflected among both private and clinic patients. Providing care to 74 percent of the State s patients, WIH s demographic and clinical statistics wholly reflect those of Rhode Island. During fiscal year 1999, 9023 deliveries were performed at WIH, 2099 among WIH Clinic and Maternal-Fetal Medicine patients. Of the total WIH deliveries, 174 had ruptured membranes before 35 weeks, 556 delivered prior to 35 weeks, 207 had multi-fetal pregnancies, 179 had gestational or chronic diabetes, 794 had hypertensive disorders in pregnancy, 539 had asthma or other respiratory disease and 163 had cardiac or vascular disease. The academic faculty and private practice community have had a consistently collaborative relationship providing access to the entire obstetrical population for cohort studies. Consequently, WIH is particularly suited for performance of clinical trials. The Maternal-Fetal Medicine Division is composed of six board-certified and one active candidate for the Maternal-Fetal Medicine boards, all of whom will support Network research protocols. The Division also employs two research nurses and a sonographer, all presently supported by NICHD funding, and three additional clinical nurses, all with extensive experience in cohort research. The Division has successfully enlisted patients (53-100 percent enlistment rates) in complex tocolysis trials and exercise, and metabolic and

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hemodynamic cohort studies with retention rates of 79-93 percent. The Division has maintained strong clinical and investigational relationships with local and regional private obstetricians, reflected in the proportions of private patients in Divisional cohort studies of 54-80 percent. The Division is presently engaged in three multicenter cohort studies funded by NICHD. It was selected by the Network in April 2000 to participate in the Beneficial Effects of Antenatal Magnesium (BEAM) Study to increase patient enlistment in this protocol and is presently beginning to enroll subjects. The Division has been funded as one of five North American sites in an international study of the maternal and perinatal impact of maternal glucose intolerance, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study. The Division is also a participant in the First and Second Trimester Evaluation of Risk (FASTER) Study examining combined biochemical and sonographic first trimester screening for Down syndrome. WIH and the Maternal-Fetal Medicine Division will enlist subjects for all Network protocols and actively participate in proposing, planning and executing Network studies. Local infrastructure available for participation in multicenter clinical trials at WIH include (1) a large patient volume and highly involved full-time and voluntary obstetrical faculty; (2) robust clinical patient, laboratory, anatomic pathology, and pharmacy databases; (3) a strong history of collaboration between Maternal-Fetal Medicine and Neonatology Divisions; (4) decades-old perinatal tissue samples and anatomic pathology; and (5) a strong Departmental commitment to outcomes research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE LACTATE PRODUCTION IN SEPSIS Principal Investigator & Institution: James, J H.; Res Ass Prof; Surgery; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 31-MAR-2005 Summary: The long-term objective of this work is to understand the changes in metabolism in sepsis in order to improve the therapy of septic patients. Sepsis results in a hypermetabolic state in which many aspects of carbohydrate metabolism are abnormal: enhanced peripheral glucose uptake and utilization, hyperlactacidemia, increased gluconeogenesis, depressed glycogen synthesis, glucose intolerance and insulin resistance. Traditionally, high circulating lactate concentration has been interpreted as tissue hypoxia or mitochondrial dysfunction. However, therapy to improve tissue perfusion does not always prevent lactate accumulation. Current understanding of energy metabolism cannot explain persistent glycolysis by welloxygenated tissues. High epinephrine levels in sepsis may cause the characteristic changes in carbohydrate metabolism through stimulation of the Na+-K+ pump in skeletal muscle. The stimulation of glycogen breakdown and lactate production in muscle by epinephrine may be closely tied to stimulation of the Na+, K+-ATPase, implying that muscle energy metabolism takes place in separate glycolytic and oxidative compartments. ATP consumption by the Na+, K+-ATPase appears to be the primary influence on ATP production in the glycolytic compartment. This proposal aims to explore these relationships in greater detail, both in septic and nonsepticrats. Studies will combine in vivo and in vitro assessments of Na+-K+ pump activity, membrane recruitment, glycolysis, glycogenolysis, ATP content and membrane permeability to Na+ and K+. The central role of epinephrine in sepsis-induced metabolic derangements will be examined in two ways (i) chronic infusion of epinephrine using implantable minipumps and (ii) chronic infusion of the beta-adrenergic blockers in sepsis. Studies in vitro will examine the persistence of epinephrine's effects on glycolysis and Na+, K+-

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ATPase activity after beta-blockade has occurred. Results of these studies will clarify metabolic relationships that are important both in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE-FAT COMMUNICATION AND METABOLIC IMPACT Principal Investigator & Institution: Phillips, Susan A.; Assistant Professor; Pediatrics; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Obesity and diabetes are increasingly significant health care concerns. Type 2 diabetes (T2D), characterized by target tissue resistance to insulin and impaired pancreatic b-cell insulin secretion, affects 5-10% of the adult population. The amount of adipose tissue is highly correlated with and may contribute to insulin resistance. Obesity affects over 20% of the population and more than 80% of type 2 diabetics are obese, suggesting that obesity may be of pathophysiological importance to subjects genetically prone to develop diabetes. Multiple lines of evidence have suggested an endocrine role of adipose tissue to modulate energy homeostasis and insulin sensitivity, other studies suggest the possibility of a dynamic "cross-talk" relationship between muscle and fat. As skeletal muscle is the principal tissue of insulin mediated glucose disposal and the major site of peripheral insulin resistance in type 2 diabetics, these data give rise to the hypothesis that adipocyte endocrine dysfunction can result in glucose intolerance and insulin resistance in skeletal muscle. The longterm goal of this proposed study is to understand the communication between fat and muscle tissue in T2D. This study aims to determine 1) if fat from diabetic subjects contributes to the development of insulin resistance in skeletal muscle, and 2) if metabolic disturbances present in skeletal muscle from diabetic subjects alters the metabolic behavior of adipose tissue. Specifically we will use adipose and skeletal muscle biopsy tissue and cultured cells from diabetic and control subjects to ask: 1) what is the metabolic behavior of isolated adipocytes or myocytes in culture and how is it altered when their physiologic proximity is restored in culture? 2) What is the effect of T2D on the metabolic behavior of these tissues and is fat-muscle communication altered when proximity is re-established in culture? 3) Can treatment of either tissue alone with anti-diabetic thiazolidinediones alter the nature of the communication between these tissues when their physiologic relationship is restored in culture? Studying fat-muscle communication will enhance our understanding of the molecular mechanisms underlying obesity-diabetes syndromes, and may suggest new treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NIDDM PRIMARY PREVENTION TRIAL (DPP-2) Principal Investigator & Institution: Kahn, Steven E.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-AUG-1994; Project End 30-JUN-2003 Summary: Non-insulin dependent diabetes mellitus (NIDDM) affects approximately 7% of the United States population, with certain population group being at increased risk of developing the disease. NIDDM is preceded by a phase of impaired glucose tolerance (IGT) and consequently individuals with IGT are at increased risk of future NIDDM. In addition to subjects with IGT, women with a history of gestational diabetes mellitus (GDM) represent a group at high risk of subsequent NIDDM. The primary specific aim of the present proposal is to determine whether subjects with IGT or newly diagnosed NIDDM can have the progression of their glucose intolerance slowed or even reversed.

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A second aim of the study is to determine the importance of factors such as insulin resistance, insulin secretion and body fat distribution in predicting individuals who are likely to respond to an intervention aimed at slowing or reversing the progression to hyperglycemia. To address these issues, we propose to study 2 populations at increased risk of developing NIDDM. We will recruit 100 Asian-Americans and 100 women with a history of GDM as part of a multicenter national study. Newly diagnosed NIDDM subjects (with a fasting plasma glucose < 140 mg/dl), identified during the screening program, will also be studied. Subjects from each population will be randomized into 4 groups: a control group, a group undertaking diet and exercise modifications, a group receiving medication (glipizide), and a group receiving diet and exercise modification and medication. Subjects will undergo these interventions for a minimum 4 year period and during this time will have sequential measurements of glucose tolerance performed. This randomization scheme allows for factorial design and analysis. In addition, measurements of body fat distribution, insulin sensitivity, insulin secretion, lipid measurements, resting metabolic rate, maximal oxygen uptake, and quality of life will be made. The data obtained from this study will answer whether the above intervention strategies in subjects at high risk of developing NIDDM and/or in subjects with recently diagnosed NIDDM, can slow or reverse the deterioration in glucose metabolism that is commonly seen in these individuals. The results of this study will have implications for future public health strategies in the United States and world-wide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NIDDM PRIMARY PREVENTION TRIAL (DPT 2) Principal Investigator & Institution: Pi-Sunyer, F Xavier.; Director; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, Ny 100191102 Timing: Fiscal Year 2002; Project Start 15-AUG-1994; Project End 14-APR-2003 Summary: The specific aims of this proposal are two-fold: the first aim is to conduct a multi-center, randomized clinical trial to evaluate the efficacy of intervening to delay or prevent the onset of non-insulin dependent diabetes mellitus (NIDDM) in individuals at increased risk of NIDDM. These individuals will consist of persons with impaired glucose tolerance (IGT) and persons with a previous diagnosis of gestational diabetes mellitus (GDM) who now have IGT. The second aim is to conduct a multi-center, randomized clinical trial to evaluate the efficacy of intervening to prevent the deterioration of previously undiagnosed NIDDM (early, asymptomatic NIDDM found during screening). All subjects will be identified by screening. At least 50% of the sample will be minority. The individuals in the first group will be those with IGT. Individuals in the second group will be those with newly diagnosed NIDDM. Criteria will be set to take only mild NIDDM for the trial, the more severely compromised patients will be referred for treatment. Individuals in both groups will be randomized into an Experimental and a Control Group. Intervention for the Experimental Group will consist of two Levels. Level I will be initiated first and will be a diet, exercise, and behavior modification program. Level II, pharmacological intervention with metformin, will be added in Level I is unsuccessful. Intervention in the Control Group will only be contact every 6 months for glucose testing. Subjects will be followed for 5 yrs with periodic testing for glucose intolerance. The major end point will be the 2 hr post glucose venous plasma. value. Twenty sites will serve as Centers and each site will enroll 98 patients. Each site will emphasize one or two racial/ethnic groups. Our Center will plan to study Caucasian and Black volunteers, although we could also study Hispanics if the protocol writers wished us to do so. There will be an initial planning phase of 1 yr, a clinical trial phase of 5 yrs, and a close-out phase of 1 yr. There will be a

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Data Coordinating Center that will collect all data and will be in charge of the central clinical laboratory. Our Center has the appropriate population base for both the IGT and the GMD parts of this clinical trial and well-trained, experienced personnel for carrying out the protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENT RECRUITMENT & CLINICAL MANAGEMENT CORE Principal Investigator & Institution: Powderly, William G.; Professor of Medicine; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) This proposal will establish a clinical core to recruit and retain HIV- infected subjects for the investigations proposed in the accompanying applications from Drs. Samuel Klein and Kevin Yarasheski. Suitable HIV subjects as well as those currently receiving treatment will be identified and recruited. This will include patients without prior antiretroviral therapy, as well as those receiving potent treatment - with or without protease inhibitors. Significant metabolic syndrome will be defined, for the purposes of these investigations as patients with an abnormal glucose intolerance, hypertriglyceridemia, and central adiposity. Patients with and without this syndrome will be recruited. Of paramount importance, will be subjects who are currently receiving protease-inhibitor based treatments who experience metabolic or other side-effects and who will choose to be switched to alternative regimens. The investigators from the clinical core will ensure that such switches are medically appropriate, maintaining viral suppression where possible using alternative potent antiretroviral regimens. Investigators from the clinical core will monitor patients both during the intensive investigations, and where relevant, during changes in antiretroviral therapy. The proposal projects that approximately twenty new patients can be enrolled in this clinical research each year, with a total enrollment target of 100 subjects. Research will be conducted in the University's General Clinical research center and at the clinics of the AIDS Clinical Trials Unit. We will match enrollment in trials to the demography of the epidemic in St. Louis. We therefore anticipate that at least 35% of enrollment will be from the African- American community and at least 10% will be women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERINATAL METABOLIC AND HORMONAL EFFECTS Principal Investigator & Institution: Devaskar, Sherin U.; Professor; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 28-FEB-2006 Summary: (provided by applicant): Perinatal Origins of Adult Disease" describes various observations of adult consequences due to altered metabolic/hormonal milieu in-utero or postnatally. Examples include 1] infants born to diabetic mothers (IDM), who, independent of their genetic predisposition, develop obesity and glucose intolerance in later life, and 2J intra-uterine growth restricted infants (IUGR) who develop syndrome X consisting of insulin resistance, obesity, and dyslipidemia with hypertension and coronary artery disease during adult life. To decipher the mechanism(s) by which this phenomenon occurs, we first characterized two rat models: 1] the streptozotocin-induced maternal diabetes where the macrosomic, hyperinsulinemic newborn offsprings develop visceral obesity, hyperinsulinemia, and glucose intolerance as adults; and 2] the prenatally starved mother where the IUGR,

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hypoinsulinemic newborn offsprings also demonstrate visceral obesity, hyperinsulinemia, and glucose intolerance as adults. Next, we focused on the recently cloned "obesity (ob) gene product (leptin) that is predominantly synthesized by adipocytes, and plays a mitogenic role in promoting fetal growth. We noted that fetal hyperinsulinemia as seen in the IDM increases while hypoinsulinemia seen with IUGR decreases fetal leptin concentrations. In addition, circulating leptin concentrations increased in the adult obese and glucose intolerant offspring of a diabetic mother and IUGR offsprings. Recently, we have demonstrated that leptin administration during the postnatal period alters skeletal muscle uncoupling proteins causing a dose-dependent decline in body weight. Postnatal leptin administration also causes an imbalance in the rat hypothalamic orexigenic (neuropeptide Y, NPY) and anorexigenic (a-melanocyte stimulating hormone, a-MSH) neuropeptides, leading to persistent changes in food intake and body weight in the adult female rat progeny. This observation gives rise to the innovative concept of in-utero/postnatal leptin concentrations predetermining the adult phenotype by "the mechanism of hormonal/metabolic imprinting." Our overall hypothesis is that in-utero/postnatal leptin concentrations with or without altered metabolic substrate availability permanently alter the mechanisms regulating food intake and energy expenditure, thereby predetermining the ultimate adult phenotype. To test this hypothesis, we propose the following specific aim: To examine the effect of postnatal intracerebroventricular (ICV) versus systemic (IP) leptin administration on hypothalamic neuropeptides that regulate food intake, and uncoupling proteins (UCP) that mediate energy expenditure, both of which determine the net body weight gain pattern in 1] the normosomic offspring of a normal rat pregnancy, 2] the macrosomic offspring of a streptozotocin-diabetic rat mother, and 3] the IUGR offspring of a prenatally starved rat mother, at d3, d10, d21, d60, and d180 in males and females. The results of our studies will test the above stated hypotheses and determine the contribution of in-utero and postnatal "leptin" in modifying the mechanisms leading to the adult phenotype predetermined by in-utero metabolic perturbations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHENOTYPIC AND FUNCTIONAL CHARACTERIZATION OF BETA CELL* Principal Investigator & Institution: Verfaillie, Catherine M.; Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: Type-1 diabetes is caused by progressive loss of insulin producing beta cells leading to glucose intolerance. Transplantation of allogeneic pancreas and, more recently, islets derived from allogeneic donors can result in reversal of glucose intolerance. However, the number of donor pancreases and/or islets that are available limits such therapy. However, the number of donor pancreases and/or islets that are available limits such therapy. Therefore, new strategies for beta cell replacement are needed. Despite recent advances in identification of mechanisms underlying beta cell development and beta cell function through targeted mutagenesis studies and immunohistochemical observation of the developing pancreas in purine or chicken embryos, our understanding of the mechanisms important for pancreatic islet development is still incomplete. Significant progress has been made in our understanding of the mechanisms important for pancreatic islet development is still incomplete. Significant progress has been made in our understanding of hematopoietic and neuronal stem cells, as well as multipotent embryonic stem (ES) cells and multipotent adult stem cells. However, the quest for identification of islet stem cells has

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been hampered by the lack of appropriate research tools including antibodies against stage-specific cell surface markers that will allow purification of viable progenitor and stem cells. Based on insights gained in the type of transcription factors responsible for islet differentiation, we will create mice genetically engineered to express fluorescent makers for specific developmental stages (HNF3- pdx1, Ngn3, Nkx6.1) that can be monitored in live cells derived from such mice. Sources for islet stem cells will include the pancreas proper, ES cells and adult tissue specific stem cells, which may be coaxed to acquire an islet fate. These three sources of cells from engineered "rainbow" mice will serve to: (1) identify islet stem cells and progenitor cells based on genetic, cell surface and functional characteristics; (2) study the function of genes known to be involved in endocrine pancreas specification and differentiation, and identify novel genes involved in pancreas development; (3) develop monoclonal antibodies against islet stem, progenitor and precursor cells; (4) develop selection methods to purify islet stem cells from three cell sources; (5) develop culture systems that will induce mature insulinproducing cell differentiation from islet stem ells ex vivo; and (6) demonstrate that islet stem cells from fetal tissue embryonal stem cells or multipotent adult stem cells have the ability to reverse diabetes in vivo. These studies will significantly advance our knowledge on the cell surface phenotype and expressed gene profile of islet stem and progenitor cells as well as the role of known and novel transcription factors in endocrine pancreas commitment and differentiation. They will also provide important cellular, antibody and genetic tools that will aid in the characterization of islet stem and progenitor cells. Finally, we will be in a position to determine whether islet stem cells, to be used for therapy of diabetes, can best be selected from the pancreas proper, from ES cells or from multipotent adult stem cells. These studies should then ultimately culminate in characterization of islet stem cell suitable for clinical therapy of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMEOSTASIS

PHOSPHODIESTERASE

REGULATION

OF

GLUCOSE

Principal Investigator & Institution: Michaeli, Tamar H.; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The objective of the proposed research is to elucidate the contribution of the camp phosphodiesterase, PDE7A, to the regulation of glucose homeostasis. Since cAMP antagonizes insulin action, cAMP phosphodiesterases can augment insulin signaling by reducing levels of cAMP pools relevant to insulin action. In particular, PDE3B augments insulin signaling in fat and liver. PDE3B, however, is not expressed in skeletal muscle. Our studies established PDE7A as a cAMP specific phosphodiesterase expressed to high levels in skeletal muscle as the particulate PDE7A2 splice variant. Our targeted disruption of the PDE7A gene in mice yielded PDE7KO mice with defects in glucose homeostasis - glucose intolerance and insulin resistance. PDE7KO mice, however, are not hyperinsulinemic and their insulin secretion in response to injected glucose is indistinguishable from that of wild type mice. Consistent with the abundant expression of PDE7A2 in skeletal muscle, and with the strong contribution of skeletal muscle to whole body glucose disposal, PDE7KO mice are impaired in insulin stimulated glucose uptake by skeletal muscle, but not by adipose tissue. Based on these observations, we hypothesize that a primary defect in PDE7KO mice is the disposal of glucose by skeletal muscle. The experimental program will examine in vivo defects of PDE7KO mice in glucose disposal, glucose and lipid metabolism, cAMP and insulin signaling, in skeletal muscle, and in liver and adipocytes.

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The contribution of pancreatic beta-cells to PDE7KO phenotypes will also be assessed. Thus, the aim of the proposal is to at understand the cross talk between the insulin and the cAMP signaling pathways and mechanisms underlying diabetogenic, metabolic perturbations in glucose homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSICAL ACTIVITY ON INSULIN RESISTANCE IN THE ELDERLY Principal Investigator & Institution: Evans, William J.; Professor; Geriatrics; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Advancing age is associated with insulin resistance, glucose intolerance, and Type 2 diabetes. Regular higher-intensity aerobic exercise reduces insulin resistance and lowers the risk of Type 2 diabetes. Nonetheless, recent cross-sectional data, based on ACSM/CDC physical activity recommendations for moderate-intensity activity on most if not all days of the week (i.e., 1000 kcal/wk), demonstrate that insulin levels are lower with regular moderate-intensity activity in middle-aged adults, suggesting a reduction in insulin resistance. Despite these crosssectional data, few well-controlled prospective studies have determined if these recommendations are appropriate to reduce insulin resistance in the elderly. Because higher-intensity aerobic exercise is not practical for a large percentage of the elderly, data are needed to determine the efficacy of moderate-intensity exercise on reducing insulin resistance. Therefore, the primary aim of this study will be to examine the influence of 1000 kcal/wk of moderate versus higher-intensity aerobic exercise on insulin-simulated glucose disposal. A secondary aim will examine if moderate and higher-intensity aerobic exercise differentially influence non-exercising activity. Recent data in the elderly suggest that regular higher-intensity activities may reduce nonexercising activity during rest of the day. We will recruit 57, 65-90 y old women and men, who will be randomized into one of the following three groups: 1) Moderateintensity activity (1000 kcal/wk at 50 percent VO2peak; 2) Higher-intensity activity (1000 kcal/wk at 75 percent VO2peak); 3) Control. Subjects will complete 12 wk of aerobic cycling with pre and post-testing for insulin-stimulated glucose disposal via the hyperinsulinemic/euglycemic clamp, glucose tolerance by an OGTT, and body composition using dual energy x-ray absorptiometry. Physical activity levels will be assessed by structured questionnaire every 3 weeks. Our primary hypothesize is that 1000 kcal/wk of moderate or higher-intensity activity will be equally effective decreasing insulin resistance in the elderly. Our secondary hypothesis is that higherintensity activity will decrease non-exercising physical activity in the elderly. This New Investigator application will provide data to base future aerobic exercise recommendations in elderly adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT STUDY--IL 6 GENOTYPES & FRAGILITY RISK IN ELDERLY Principal Investigator & Institution: Walston, Jeremy D.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The purpose of this study is to identify single or combinations of IL-6 gene variants that associate with elevations of serum IL-6 in the Women's Health and Aging I and II cohorts, and to determine the relationship between these genotypes, skeletal muscle strength, and the syndrome of frailty in the same

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group. The long term goal of this pilot study is to identify clinically relevant IL-6 variants and translate them into test that will identify those older adults at highest risk for losing independence through the development of frailty or its components. Another long-term goal is to develop further studies in order to determine if these clinically relevant gene variants can be markers for those at highest risk for disease complications and poor outcomes. IL-6 mediated chronic inflammation plays a role in the development of frailty in older adults through its contribution to the development of muscle mass and strength decline, glucose intolerance, and anemia. The etiology of this increase in some older adults and not others is multifactorial and includes increased prevalence of acute and chronic disease, declines in sex steroids, and genetic variation. Several specific IL6 gene polymorphisms correlate with increased serum IL-6 and worse outcomes in several inflammatory disease states including rheumatoid arthritis, multiple sclerosis, and Sjogren's syndrome. We hypothesize that specific IL-6 gene variants, individually or in combinations, contribute to higher levels of serum IL-6 in older adults. In order to test this hypothesis, we will genotype consented WHAS 1 and 2 participants for 5 IL-6 single nucleotide polymorphic variants, determine the association between the IL-6 single and combined gene variants and previously measured baseline visit serum IL-6 in the same cohort, and then determine the relationship between these alleles and skeletal muscle strength and with frailty using the expertise and experience of both the Genetics Research Core and the Biostatistics Research Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL MECHANISMS OF AGE DEPENDENT BONE LOSS Principal Investigator & Institution: Williams, John P.; Associate Professor; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: Osteoporosis is the most common debilitating bone disease affecting 24 million people in the U.S. An estimated 50 percent of women over 45 and 90 percent of women over 75 years of age have osteoporosis, of which approximately half will suffer osteoporotic fractures. The estimated cost of osteoporosis and related fractures is 7-10 billion dollars per year. Bone resorption by osteoclasts is an energy intensive process, requiring ATP hydrolysis by an H+-ATPase to drive proton secretion. Age-dependent changes in bone mass are accompanied by age-dependent changes in other parameters, including glucose intolerance. Osteoclasts are glucose responsive cells that resorb bone in a glucose concentration dependent manner with a Km of 3 mM. The data presented here indicate that osteoclasts have glucose concentration dependent changes in 1) ATP synthesis, 2) phosphate uptake, 3) tyrosine phosphorylation, and 4) phosphatidylinositol 3-kinase activity. In view of the high metabolic demands of bone resorption, I hypothesize that glucose directly alters the activity of osteoclasts by modulating critical signal transduction processes in these cells. The proposed research will define the molecular mechanisms and metabolic requirements responsible for regulating these signal transduction processes. The Specific Aims are to: I: Characterize The Expression Of Glucose Transport Protein (S) In Osteoclasts. A. Determine the effect of bone attachment on GLUT2 expression in osteoclasts. B. Determine whether glucose transporters are translocated to the plasma membrane in response to bone attachment. II: Characterize Metabolic Elements That Govern Osteoclast Activity. A. Determine the rate limiting steps in glucose metabolism by osteoclasts. B. Characterize the glucose dependence of metabolic pathways. III: Identify Ket Signaling Pathways That Regulate Osteoclast Metabolism. A. Determine and characterize the role of glucose in osteoclastic

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phosphatidylinositol-dependent signaling pathways. B. Determine the role of glucose in modulating changes in tyrosine phosphorylation of specific proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRIMARY PREVENTION PROGRAM -DATA COORDINATING CENTER Principal Investigator & Institution: Fowler, Sarah E.; Research Professor; Statistics; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 20-AUG-1994; Project End 31-MAY-2003 Summary: (Directly incorporated from the application) The Biostatistics Center of The George Washington University proposes to work in cooperative agreement with the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) to serve as the Data Coordinating Center (DCC) for a proposed multi-center clinical trial of the primary prevention of non-insulin dependent diabetes mellitus (NIDDM). Adiposity and inactivity have been established as critical factors in the etiology of glucose intolerance and are strongly associated with increased risk of glucose intolerance. We propose to determine the safety and efficacy of an intensive lifestyle intervention or prophylactic use of an oral hypoglycemic agent on the incidence of NIDDM among high risk patients (obese, minority, family history of NIDDM, history of gestational diabetes mellitus) in a state of impaired glucose tolerance (IGT). The objective of the one year planning phase is to develop a protocol, operations manual and data collection forms to be implemented in a five year full-scale clinical trial. The trial will require large-scale screening and randomization of 4,000 high risk patients with a diagnosis of IGT over a one year period in 20 clinical centers. Eligible patients will be randomized to "conventional" dietary counseling or one of the comparison groups (intensive lifestyle intervention or an oral hypoglycemic agent). Randomized patients will be followed for a minimum of four years with quarterly follow-up visits. Conversion from a state of IGT to overt NIDDM will be determined by semi-annual 2-hour oral glucose tolerance tests (OGTTs) following a 75 g glucose load confirmed by a central laboratory. Covariates and secondary outcomes include carotid ultrasound imaging, electrocardiograms, serum lipids, albumin excretion rate, adiposity, insulin sensitivity, hemoglobin A1c, and fundus photographs. The specific aims of the DCC are to provide centralized support and biostatistical consultation in the development of the patient management protocols, operations manual, data collection forms and randomization procedures; implementation of a data processing system including data quality assessment; interim analysis of protocol performance, patient safety and treatment efficacy; and final analysis for publication of the results in collaboration with the clinical investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGRAM PROJECT IN BIOMEDICAL OUTCOMES OF AGING Principal Investigator & Institution: Minaker, Kenneth L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-AUG-2007 Summary: GRANT=6423578;P01AG This application seeks renewed support for the Program Project in Biomedical Outcomes of Aging. We hypothesize that age-associated growth hormone declines influence cardiac and peripheral muscle function during congestive heart failure compensation. Finally, we hypothesize that age-related decrements in insulin release and action lead to the glucose intolerance of aging. Building on our preliminary observations we have formulated a common hypothesis

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that trophic factor restoration (employing exogenous agents?GHRH, testosterone, GLP/Exendin) will not only correct the underlying deficiency states but be useful tools to correct the impaired tissue structure or function, and improve the symptoms of functional loss in settings where tissue related illnesses have resulted (CHF, sarcopenia and diabetes mellitus). On a more fundamental level we will explore the mechanisms underlying correction of the "trophic endocrinopathy of aging." Protein synthesis in the heart, peripheral muscle metabolism, growth factors, and hormonal release and action will all be examined before and after hormonal substitution. Common study designs of hormone replacement protocols will be employed to examine structural and functional changes. The shared resources and scientific collaborations int his renewal encompass data management, common analytical procedures (e.g. radioimmunoassays, body composition analysis) and a supply-purchasing system. The Program Project also forms an excellent forum for training of gerontologic investigators, particularly Ph.D. and M.D. trainees entering our institutional programs. The relocation The relocation of the Program Project to the Massachusetts General Hospital following the Principal Investigator's move and the establishment Medicine Unit at the Massachusetts General Hospital opens and extends collaborations. Our new MGH collaborator is Dr. Laurence Katznelson, Endocrine Division. The extensions are Dr. Joel Habner, collaborator of Drs. Elahi and Minaker for many years," and Dr. Ronenn Roubenoff Joseph Kehayias and Ms. Virginia Hughes at the USDA Human Nutrition Research Center on Aging at Tufts University. The significance of each project rests in its contribution to the understanding of physiologic and pathophysiologic mechanisms relevant to the health and the common diseases affecting aging Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRAMMING GLUCOCORTICOID SECRETION DURING FETAL LIFE Principal Investigator & Institution: Phillips, David I.; Professor; University of Southampton Highfield Southampton, Timing: Fiscal Year 2002; Project Start 27-SEP-2001; Project End 30-JUN-2004 Summary: (provided by applicant): Epidemiological studies have shown that low birthweight in combination with adult obesity is associated with a marked increase in the prevalence of the metabolic or insulin resistance syndrome (insulin resistance, hypertension, dyslipidaemia and glucose intolerance). This syndrome is in turn associated with an increased risk of both type 2 diabetes and atherosclerotic vascular disease. These observations have led to the hypothesis that adaptations made by the fetus in response to undernutrition give rise to persisting changes in metabolism which lead to insulin resistance and the metabolic syndrome. Although the nature of these changes are not understood, animal studies and preliminary human observations made by the Principal Investigator have led to the hypothesis that in utero resetting of the hypothalamic-pituitary-adrenal (EPA) axis resulting in increased secretion of the adrenal stress hormone, cortisol, is an important change which may initiate the metabolic syndrome. The aim of the studies are to characterize the nature of the abnormality of the HPA axis in adults who were small at birth and the way in which this abnormality interacts with adult obesity to determine the prevalence of the metabolic syndrome or its components. It is expected that the information from these studies will form a first step towards the development of pharmacological strategies aimed at reducing the deleterious effects of low birthweight on adult health. It also has the potential to provide outcome measures in trials of maternal nutrition or other interventions to improve fetal growth and well-being, and by identifying affected

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individuals early in life may allow specific targeting of public health interventions (e.g. obesity reduction). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOLERANCE

QUANTITATION

OF

FACTORS

REGULATING

GLUCOSE

Principal Investigator & Institution: Bergman, Richard N.; Professor of Physiology and Biophysics; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-AUG-1981; Project End 31-DEC-2002 Summary: Type 2 diabetes is a complex disease which is caused by a slow progression of decreased glucose tolerance, followed by hyperglycemia. it is of great interest to understand the complex patterns of changes in metabolic function which precede overt hyperglycemia. Three components which can contribute to glucose intolerance are insulin resistance, impaired B-cell function, and reduced glucose effectiveness. The latter process is the ability of glucose itself to enhance carbohydrate disposal and suppress endogenous glucose output. We have obtained data supporting the concept that in normal individuals B-cell function increases to compensate for insulin resistance caused by hereditary or environmental factors. In fact, the mathematical product of insulin sensitivity and insulin secretion is approximately constant. The mechanisms responsible for the hyperbolic relationship between insulin sensitivity and insulin secretion are studied in this proposal. The time course of changes in glucose tolerance and B-cell response will be monitored to elucidate the events which account for the hyperbolic interaction, and to identify the signals in blood which are responsible for this striking relationship. Whether a similar, but less efficient hyperbolic relationship can be maintained when B-cell function is impaired will be examined. Also, we will examine the importance of individual metabolic precesses to glucose effectiveness. The role of glucose production by liver or kidney, as well as glucose uptake by insulin independent and insulin dependent tissues will be assessed. Also examined will be the changes which take place in function of individual tissues when glucose effectiveness changes. These studies should provide an integrated picture of the means by which the intact organism maintains normal maintenance of glucose tolerance when small changes in Bcell function are imposed, and could well provide new insights into the pathogenesis and potential treatment targets for Type 2 diabetes and the prediabetic state. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAGE AND MECHANISMS OF VASCULAR AND MONOCYTE DYSFUNCTION Principal Investigator & Institution: Schmidt, Ann Marie.; Professor; Physiology/Cellualr Biophysics; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-FEB-1999; Project End 31-JAN-2005 Summary: Sustained endothelial and mononuclear phagocyte dysfunction is critical to the pathogenesis of chronic vascular disorders. Non-enzymatic glycoxidation of proteins and lipids forming Advanced Glycation Endproducts (AGEs) in the vasculature and tissues is accelerated in atherosclerosis, diabetes and renal failure. Interaction of AGES with Receptor for AGE (RAGE) on endothelium and monocytes perturbs cellular properties critical to vascular and tissue homeostatic processes, and causes chronic cellular activation. The central hypothesis of the Program Project is that AGE-RAGE-

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Glucose Intolerance

mediated modulation of endothelial and monocyte functions compromises physiologic effector mechanisms and eventuates in aggressive atherosclerosis, delayed wound repair, and impaired resolution of local inflammation. Employing glucose intolerance as the stimulus for enhanced AGE formation, our pilot studies have shown that antagonism of AGE-RAGE interaction suppresses accelerated atherosclerosis, ameliorates wound healing and diminishes inflammatory consequences of soft tissue infection. Project 1 will exploit our recently developed murine model of accelerated atherosclerosis associated with glucose intolerance to probe the role of RAGE in rapid formation of vascular lesions. Project 2 will extend our concept to a secondary intention wound model in insulin- resistant mice in which AGE-RAGE-mediated cellular dysfunction underlies compromised tissues reparative mechanisms. Project 3 will focus on local inflammation/infection in AGE-rich soft tissues using a model of gingivitis triggered by bacterial infection. The overlapping host response mechanisms triggered by atherogenesis, wound repair and local inflammation, the intimate involvement of endothelium and monocytes, as well as the central role of AGE binding to RAGE, provide the basis for close interactions among the three Projects. By collaborative studies between each of the Projects, the contribution of RAGE will be determined using transgenic mice and mutated RAGE molecules. At the end of this Program Project, we expect to have generated new and important information related to vascular and monocyte dysfunction underlying accelerated atherosclerosis, impaired wound healing and the compromised host response to local inflammation common to disorders characterize by tissue deposition of AGEs. These data should provide insight into a novel target for the development of future therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF INSULIN GENE EXPRESSION Principal Investigator & Institution: Montminy, Marc R.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002; Project Start 15-JUN-1995; Project End 30-JUN-2004 Summary: The homeobox protein pdx1 functions importantly in pancreatic development and in glucose homeostasis. Targeted disruption of the pdx1 gene leads to pancreatic agenesis in pdx1 -/- homozygotes, and pdx +/- heterozygotes develop glucose intolerance as adults. Inactivating mutations in the human pdx1 gene are correlated with maturity onset diabetes of the young, further underscoring the importance of this factor for glycemic control. The long term objective of this proposal is to elucidate the mechanism by which pdx1 stimulates the expression of cellular target genes during development and in response to glucose. Two features of the pdx polypeptide appear to be particularly critical in this regard; a conserved pentapeptide motif that mediates cooperative DNA binding with the ubiquitous homeodomain protein pbx, and an N-terminal trans-activation domain whose activity is induced in response to glucose stimulation. The major hypothesis to be tested is that glucose regulates the transcriptional activity of the pdx/pbx complex by promoting complex formation with the co-activator CBP via a phosphorylation dependent mechanism. This hypothesis will be tested in the following specific aims: 1. We will characterize the mechanism by which the conserved pentapeptide motif in pdx promotes interaction with pbx, and we will evaluate the importance of pdx/pbx complex formation for pancreatic development and glucose homeostasis in transgenic mice. 2. We will characterize a glucose responsive trans-activation domain in pdx-1, and we will identify residues in pdx that are phosphorylated in response to glucose stimulation. 3. We will examine the mechanism by which pdx interacts with the signal dependent co-activator

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CBP, and we will evaluate whether glucose promotes recruitment of CBP to pdx by a phosphorylation dependent mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ATHEROSCLEROSIS

OF

FATTY

ACID

BINDING

PROTEINS

IN

Principal Investigator & Institution: Linton, Macrae F.; Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Insulin resistance is a condition associated with a cluster of abnormalities including hypertension, glucose intolerance, hypertriglyceridemia, obesity and premature coronary artery disease. Understanding the molecular basis of the link between insulin resistance and these pathological states has been a difficult task. Elevated plasma levels of free fatty acids are a common hallmark of insulin resistance. Cytoplasmic fatty acid binding proteins (FABP) are small cytoplasmic proteins that bind a variety of fatty acids and are expressed in a tightly regulated, tissue specific manner. Proposed functions of cytoplasmic FABP include trapping and trafficking of fatty acids within cells and cell signaling. Targeted disruption of the aP2 allele has been shown to uncouple obesity and insulin resistance, indicating an important role for aP2 in the insulin resistance. Preliminary studies indicate that aP2 promotes atherosclerosis and macrophage foam cell formation in apoE deficient mice. Mall, a closely related FABP, is also expressed by adipocytes and macrophages and is up-regulated in aP2 deficient mice. The goal of this project is to investigate the impact of aP2 and mall-deficiency on insulin resistance and atherosclerosis. To this end, murine bone marrow transplantation will be used to generate mice chimeric for aP2 and or mall expression by macrophages and or adipocytes allowing the investigation of the relative cell-specific contributions of expression of these genes to atherosclerosis and insulin resistance. Finally, in vitro studies will investigate the role of aP2 and mall in macrophage foam cell formation. By providing new insights into the link between insulin resistance and atherosclerosis, these studies may lead to new therapeutic approaches to diabetes and coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF GLP-1 IN NORMAL AND ABNORMAL GLUCOSE TOLERANCE Principal Investigator & Institution: D'alessio, David A.; Associate Professor of Medicine; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 30-SEP-1999; Project End 31-MAY-2008 Summary: (provided by applicant): Type 2 diabetes constitutes an enormous health burden in the United States, and despite the increasing prevalence of this disease there are still major gaps in understanding the underlying causes. The overall goal of this proposal is to determine the role of the GI hormone glucagon-like peptide 1 (GLP-1) to regulate glucose tolerance in non-diabetic persons and patients with type 2 diabetes. In healthy humans GLP-1 stimulates insulin secretion, and together with other signals arising from the gut during meal absorption, accounts for 30-60% of the insulin secreted. Studies in animals and humans indicate that blocking the action of GLP-1 causes glucose intolerance. In persons with type 2 diabetes, and other forms of abnormal glucose tolerance, the augmentation of insulin secretion by stimuli from the gut, such as

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GLP-1, is severely impaired. The findings from therapeutic trials of GLP-1 and GLP-1agonists support the currently favored model that GLP-1 acts as a hormone. However, recent findings by our group and others have shown that GLP-1 may signal primarily through neural pathways, likely originating in the splanchnic bed. Based on this data we propose that the action of endogenous GLP-1 to stimulate insulin secretion is through a neural reflex originating in the immediate distribution of the portal vein. The specific aims of this project will determine: 1) whether the stimulation of insulin secretion by endogenous GLP-1 in humans is mediated by parasympathetic signaling, and whether this mechanism is abnormal in persons with type 2 diabetes; 2) the mechanisms and pathways of neural activation by which endogenous GLP-1 promotes insulin secretion; 3) the effect of hepatic-portal denervation on glucose tolerance and the response to GLP1. Establishing the role of a neural system by which intestinal GLP-1 acts is important for understanding how post prandial insulin secretion is regulated and why the incretin axis is impaired in diabetic patients. The results of these studies will add to the understanding of the regulation of glucose metabolism by GLP-1 and the incretin axis, and contribute to the development of new strategies to treat type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TELOMERE INDUCED GENOMIC INSTABILITY IN PREMATURE AGING Principal Investigator & Institution: Chang, Sandy S.; Assistant Professor; Molecular Genetics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAY-2007 Summary: (provided by applicant): Genetic studies of human progeric syndromes have furthered our understanding of the molecular mechanisms of the aging process. Mutations in Wrn causes Wemer Syndrome (WS), a disease characterized by premature aging, elevated genomic instability and cancer. WS fibroblasts prematurely senescence due to telomere shortening, suggesting the possibility that telomere dysfunction collaborates with Wrn loss to generate WS. Telomeres function to prevent chromosomal ends from being recognized as double-strand DNA breaks and confer genome stability. It has been postulated that telomere shortening serves as a molecular clock that eventually signals replicative senescence. WS cells senescence while still possessing long telomeres, suggesting that they may be hypersensitive to telomere shortening. This hypothesis is supported by the observation that the senescence phenotype observed in WS cells can be rescued by overexpression of telomerase, suggesting that one consequence of the WS defect is the acceleration of normal telomere-based senescence. Mice lacking WRN do not display obvious aging phenotypes, and I hypothesize that manifestation of the WS phenotype requires the presence of critically short telomeres. Mouse telomeres are normally too long for the required telomere attrition to take place during the aging process. To test experimentally the hypothesis that manifestation of the WS phenotype in WRN-/- mice requires critical telomere shortening, telomere lengths were shortened genetically via successive intercrossings of WRN-/- mTERC-/- mice. Compound mutant mice with short dysfunctional telomeres exhibited early onset of aging phenotypes, including alopecia, cataract formation and glucose intolerance and died prematurely. These exciting results suggest that our mouse model recapitulates features of WS observed in human patients. Our immediate goal is to characterize additional aging phenotypes in these mice and to correlate the onset of premature aging with genomic instability induced by telomere dysfunction. We are also probing for molecular mechanisms that may be responsible for the observed aging phenotypes in

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our mouse model. These studies should illuminate the roles of Wrn and dysfunctional telomeres during human aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNIT Principal Investigator & Institution: Zeisel, Steven H.; Professor and Chair; Nutrition; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-SEP-2004 Summary: We propose a CNRU that is specifically designed to enhance the translation of basic science information and technology into population-based and clinical nutrition research, and also to facilitate the transfer of ideas and information in the opposite direction. These population-based studies are the major approach for preention information in the opposite direction. These population-based studies are the major approach for prevention research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures that typify nutrition versus drug studies. A major reason to locate a CNRU at UNC-CH is the strength and interdisciplinary breadth of our research programs in nutrition. Fifty-five active investigators conduct research that spans areas of basic, clinical and applied science relevant to human nutrition, including clinical nutrition, metabolic biochemistry, molecular biology, gastroenterology, hepatology, pharmacology, health behavior, nutrition epidemiology, physiology, oncology, and endocrinology. Excellent graduate students and postdoctoral fellows are working with CNRU investigators, and CNRU faculty are the awardees for four T32 training grants from the NIDDK, NHLBI, NIEHS and NCI. Our research base generates more than $20 million in annual NIH-funded (or equivalent), nutrition-related research support. CNRU faculty are appointed in many departments including nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, pathology, and environmental. Steven Zeisel, MD serves as CNRU director, and Rosalind Coleman, MD as associate director. An internal governance committee (consisting of the director, associate director, three core directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity, and continuity of directors, and two representatives of thee CNRU faculty) will maintain the quality, objectivity and continuity of directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity and continuity of policies that govern the CNRU. An external advisory committee will be established. The Administrative Core will be responsible for management of the CNRU and will provide biostatistical support, grant pre-review services, facilitation of access to research populations, computer support, an enrichment program, a medical student education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative, a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a young investigator award, community outreach and public education. Several of these activities will be conducted in collaboration with the UNC-CH General

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Glucose Intolerance

Clinical Research Center. The proposed Translational Core for Population Studies, led by Lenore Kohlmeier, Ph.D., is designed to facilitate the translation of new findings and technology into outgoing research projects and to stimulate the incorporation of state of the art methodology in population based human nutrition studies. The core services will be in five areas: incorporation of biomarkers of dietary intake in ongoing studies, technical support in the preparation of multi-mediate based dietary assessment, statistical support in the design and analyses of epidemiology studies, support in the preparation of an access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical nutritional data on foods and nutrient supplements for estimation of intakes and support5 with the complex statistical nutritional data on foods and nutrition support in the preparation of multi media based dietary assessment statistical in the design and analyses of epidemiological studies, support in the preparation in the preparation of and access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of the Molecular Biology and Nutritional Biochemistry Core, directed by Melinda Beck, Ph.D., is to provide a state-of-the-art facility for nutrition research investigators. The core will serve as an educational and training resource for the development and application of molecular biology techniques and biomarkers for nutritional research. It will provide a number of specialized techniques requested by CNRU investigators. In addition, the Core will provide consultation and assistance to investigators who may just be beginning to use molecular techniques and biomarkers in their research. The Nutrition Intervention Core, directed by Marci Campbell, Ph.D., will provide expertise and state-of-the-art resources and techniques for developing and evaluation nutritional interventions aimed at promoting health and preventing disease and populations at risk. CNRU. Investigators will have access to intervention development and tracking tools, and will receive help and consultation on their application to each project. Five junior investigators propose P/F projects on Selenium and arsenic toxicity. Gene targeted animal models for CVD, Church-based nutrition intervention in African Americans, Epidemiology of glucose intolerance during pregnancy, and Vitamin D therapy for bone disease in cystic fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR AND MONOCYTE DYSFUNCTION IN WOUND REPAIR Principal Investigator & Institution: Andres, Giuseppe; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: Tissue and vascular deposition of Advanced Glycation Endproducts (AGEs), irreversible products of glycoxidation of proteins and lipids, occurs during normal aging and is accelerated by concomitant glucose intolerance or renal failure. Thus, normal host reparative mechanisms, such as those set in motion by wounding must proceed in an environment rich in AGEs. Cells critical to orchestration of wound healing, especially endothelial cells (ECs) and mononuclear phagocytes (MPs), express Receptor for AGE (RAGE), a principal cell surface binding site for AGEs. Consequent to engagement bu AGEs, RAGE brings about changes in cellular functions central to tissue reparative mechanisms triggered during the inflammatory, proliferative and remodeling phases of healing. Pilot studies using a secondary intention would model in glucose

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intolerant mice, the latter to accelerate AGE deposition, have shown delayed healing compared with control animals. Wound closure in this model is enhanced, almost to levels in euglycemic controls, by local or systemic administration of a truncated hypothesis that AGE binding to RAGE on critical cellular targets, especially ECs and MPs, modulates their participation in reparative processes by promoting sustained activation, leading to a chronic, destructive inflammatory response. Our specific aims are: (1) to analyze, in the secondary intention wound model, the effect of sRAGE on differences in the reparative response in glucose-intolerant amd euglycemic mice, by monitoring activation of ECs, influx and activation of MPs, production of proinflammatory cytokines, growth factors, and the balance of collagen synthesis/degradation; (2) to produce new transgenic murine models for evaluating the contribution of AGE-RAGE interaction to wound healing by cross-breeding transgenic (Tg) mice with targeted overexpression of full- length RAGE or a dominant negative form of the receptor in MPs or ECs with glucose intolerant mice, and to determine the effect on the reparative response: and (3) to identify determinants on RAGE mediating interaction with AGEs. Project 2 will work closely with Projects 1&3 and will obtain technical assistance from the Cores. Collaborative interactions will include: development and characterization of Tg RAGE mice (Projects 1&3 and Core C), collagen/collagenase evaluation (Project 2), transcriptional analysis of RAGE expression (Project 1), and pathologic study of tissues (Core B). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “glucose intolerance” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for glucose intolerance in the PubMed Central database: •

Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor --1 (Pref-1). by Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151920

•

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans ROLE OF THE SPLANCHNIC BED. by Sacca L, Vigorito C, Cicala M, Ungaro B, Sherwin RS.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370977

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Role of parathyroid hormone in the glucose intolerance of chronic renal failure. by Akmal M, Massry SG, Goldstein DA, Fanti P, Weisz A, DeFronzo RA.; 1985 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423657

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with glucose intolerance, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “glucose intolerance” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for glucose intolerance (hyperlinks lead to article summaries): •

A comparison of left ventricular abnormalities associated with glucose intolerance in African Caribbeans and Europeans in the UK. Author(s): Chaturvedi N, McKeigue PM, Marmot MG, Nihoyannopoulos P. Source: Heart (British Cardiac Society). 2001 June; 85(6): 643-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359744

•

A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome. Author(s): Williams DE, Prevost AT, Whichelow MJ, Cox BD, Day NE, Wareham NJ. Source: The British Journal of Nutrition. 2000 March; 83(3): 257-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10884714

•

A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese. Author(s): Ko GT, Chan JC, Yeung VT, Chow CC, Tsang LW, Cockram CS. Source: European Journal of Epidemiology. 2001; 17(3): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11680550

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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•

A new familial syndrome characterized by pigmentary retinopathy, hypogonadism, mental retardation, nerve deafness and glucose intolerance. Author(s): Edwards JA, Sethi PK, Scoma AJ, Bannerman RM, Frohman LA. Source: The American Journal of Medicine. 1976 January; 60(1): 23-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1251844

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A preliminary assessment of acculturation and its relationship to body size and glucose intolerance among Blacks in the US Virgin Islands. Author(s): Tull ES, Ambrose JJ, Chambers E. Source: Ethn Dis. 2003 Winter; 13(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723007

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A quantitative trait locus that accounts for glucose intolerance maps to chromosome 8 in hereditary obese KK-A(y) mice. Author(s): Suto J, Sekikawa K. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 November; 26(11): 1517-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439655

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Abdominal obesity and glucose intolerance in middle-aged women in the United Arab Emirates. Author(s): al Tajer SS, Hossain MM, Pugh RN. Source: Journal of Public Health Medicine. 1995 September; 17(3): 362-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8527192

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Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. Author(s): Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5587-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466357

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Absence of capillary microangiopathy in oral contraceptive users with glucose intolerance. Author(s): Goldzieher JW, Villegas-Castrejon H, Cervantes A, Maqueo M, Siperstein MD. Source: Obstetrics and Gynecology. 1978 January; 51(1): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=619342

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Age and glucose intolerance: effect of fitness and fatness. Author(s): Reaven G. Source: Diabetes Care. 2003 February; 26(2): 539-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547897

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•

Age, body mass index and 2-hour plasma glucose are the major determinants of blood pressure in Chinese women newly diagnosed to have glucose intolerance. Author(s): Ko GT, Chan JC, Cockram CS. Source: International Journal of Cardiology. 1999 April 30; 69(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10362370

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Age-related alteration of pancreatic beta-cell function. Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance. Author(s): Shimizu M, Kawazu S, Tomono S, Ohno T, Utsugi T, Kato N, Ishi C, Ito Y, Murata K. Source: Diabetes Care. 1996 January; 19(1): 8-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8720525

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Age-related glucose intolerance in hyperthyroid patients. Author(s): Ikejiri K, Yamada T, Ogura H, Matsumoto, Kobe. Source: Diabetes. 1978 May; 27(5): 543-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=648744

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Aging exaggerates glucose intolerance following injury. Author(s): Watters JM, Moulton SB, Clancey SM, Blakslee JM, Monaghan R. Source: The Journal of Trauma. 1994 November; 37(5): 786-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7966476

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Amniotic fluid insulin at 14-20 weeks' gestation: association with later maternal glucose intolerance and birth macrosomia. Author(s): Carpenter MW, Canick JA, Hogan JW, Shellum C, Somers M, Star JA. Source: Diabetes Care. 2001 July; 24(7): 1259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11423512

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An assessment of glucose intolerance in acromegaly and its response to medical treatment. Author(s): Wass JA, Cudworth AG, Bottazzo GF, Woodrow JC, Besser GM. Source: Clinical Endocrinology. 1980 January; 12(1): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7379314

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Antihypertensives and glucose intolerance. Author(s): Ibrahim B. Source: The American Journal of Cardiology. 1993 February 15; 71(5): 493-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8430656

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Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Author(s): Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Source: Circulation. 2002 October 15; 106(16): 2085-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379578

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Are African American patients at a higher risk for olanzapine-induced glucose intolerance? Author(s): Ananth J, Gunatilake S, Aquino S, Bach V, Costa J. Source: Psychopharmacology. 2001 September; 157(3): 324-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11605090

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Are the increased Lp(a) levels in hemodialysis patients related to glucose intolerance and hemodialysis duration? Author(s): Elisaf M, Siamopoulos KC. Source: Nephron. 1996; 74(3): 623-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938695

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Assessment of glucose intolerance and insulin sensitivity in polycystic ovary syndrome. Author(s): Yildiz BO, Gedik O. Source: Reproductive Biomedicine Online. 2004 June; 8(6): 649-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15169580

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Association between a low adipose tissue content of polyunsaturated fatty acids and both glucose intolerance and hypertriglyceridemia in apparently healthy men. Author(s): Carlson LA, Walldius G. Source: Acta Med Scand. 1975 April; 197(4): 295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1136857

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Association between polycystic ovary syndrome and glucose intolerance during pregnancy. Author(s): Lesser KB, Garcia FA. Source: The Journal of Maternal-Fetal Medicine. 1997 September-October; 6(5): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360193

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Association between the SstI polymorphism of the apolipoprotein C-III gene, glucose intolerance and cardiovascular risk in renal transplant recipients. Author(s): Rodrigo E, Gonzalez-Lamuno D, Ruiz JC, Fresnedo GF, Isla D, Cotorruelo JG, Zubimendi JA, de Francisco AL, Garcia-Fuentes M, Arias M. Source: Transplantation Proceedings. 2002 February; 34(1): 379. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959336

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Glucose Intolerance

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Association of HELLP syndrome with autoimmune antibodies and glucose intolerance. Author(s): Weitgasser R, Spitzer D, Kartnig I, Zajc M, Staudach A, Sandhofer F. Source: Diabetes Care. 2000 June; 23(6): 786-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10840997

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Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Author(s): Haap M, Fritsche A, Mensing HJ, Haring HU, Stumvoll M. Source: Annals of Internal Medicine. 2003 November 18; 139(10): 869-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623634

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Association of HLA antigens with glucose intolerance following renal transplantation. Author(s): d'Apice AJ, Mathews JD, Tait BD, Kincaid-Smith P. Source: Tissue Antigens. 1978 May; 11(5): 423-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=358493

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Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Author(s): Shima Y, Tsukada T, Nakanishi K, Ohta H. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 June 22; 274(2): 167-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9694585

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Audit of maternal and fetal outcomes in women treated for glucose intolerance during pregnancy. Author(s): McIntyre HD, Begg LM, Parry AF, Oats J. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 February; 42(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926637

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Autoantibodies to pancreatic hsp60 precede the development of glucose intolerance in patients with cystic fibrosis. Author(s): Jensen P, Johansen HK, Carmi P, Hoiby N, Cohen IR. Source: Journal of Autoimmunity. 2001 September; 17(2): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591125

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Beta 2-sympathomimetic activation as a cause of posthypoglycemic glucose intolerance. Author(s): Petersen KG, Kerp L. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1988 March; 20(3): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3290078

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Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. Author(s): Dunaif A, Finegood DT. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 March; 81(3): 942-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772555

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Birthweight in women with potential gestational diabetes mellitus--an effect of obesity rather than glucose intolerance? Author(s): Lauszus FF, Paludan J, Klebe JG. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 July; 78(6): 520-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10376862

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Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK. Author(s): Unwin N, Harland J, White M, Bhopal R, Winocour P, Stephenson P, Watson W, Turner C, Alberti KG. Source: Journal of Epidemiology and Community Health. 1997 April; 51(2): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9196645

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Can glucose intolerance and/or diabetes be predicted in patients treated with rhGH? Author(s): Hokken-Koelega AC. Source: Br J Clin Pract Suppl. 1996 August; 85: 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8995034

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Cardiovascular risk factors in African-Americans with varying degrees of glucose intolerance. Author(s): Osei K, Gaillard T, Schuster DP. Source: Diabetes Care. 1999 September; 22(9): 1588-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480533

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Characteristics of glucose intolerance in alcoholics with liver cirrhosis during abstinence especially with reference to catecholamines. Author(s): Ihori M, Harada T, Omori R, Ueda H. Source: Gastroenterol Jpn. 1978; 13(5): 366-73. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=729998

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Chronic renal failure and secondary hyperparathyroidism are responsible for glucose intolerance and impaired insulin secretion of aging. Author(s): Massry SG, Fadda GZ. Source: J Endocrinol Invest. 1992; 15(9 Suppl 6): 73-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1300343

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Cigarette smoking, oral moist snuff use and glucose intolerance. Author(s): Persson PG, Carlsson S, Svanstrom L, Ostenson CG, Efendic S, Grill V. Source: Journal of Internal Medicine. 2000 August; 248(2): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10947888

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Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Author(s): Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Source: Lancet. 2002 May 18; 359(9319): 1740-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049864

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Classification of glucose intolerance in the aged based on hemoglobin A1. Author(s): Nakao J, Orimo H, Ito H. Source: The Tohoku Journal of Experimental Medicine. 1980 November; 132(3): 305-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7466810

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Clinical characteristics of transient glucose intolerance during acute diarrhoea. Author(s): Ozmert E, Yurdakok K, Aslan D, Yalcin SS, Yardim M. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 October; 88(10): 1071-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565451

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Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidaemia or glucose intolerance. Author(s): Worm D, Kirk O, Andersen O, Vinten J, Gerstoft J, Katzenstein TL, Nielsen H, Pedersen C. Source: Hiv Medicine. 2002 October; 3(4): 239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444941

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Clinical significance of compound quinestrol-caused glucose intolerance. Author(s): Zhu XX, He DH, Wang ZG, Chen JH, He WT, Qiu CL, Zhong XL. Source: Chinese Medical Journal. 1980 September; 93(9): 651-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6775900

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Community screening for glucose intolerance in middle-aged Icelandic men. Deterioration to diabetes over a period of 71/2 years. Author(s): Sigurdsson G, Gottskalksson G, Thorsteinsson T, Davidsson D, Olafsson O, Samuelsson S, Sigfusson N. Source: Acta Med Scand. 1981; 210(1-2): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7293824

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Comparability of blood glucose concentrations measured in different sample systems for detecting glucose intolerance. Author(s): Haeckel R, Brinck U, Colic D, Janka HU, Puntmann I, Schneider J, Viebrock C. Source: Clinical Chemistry. 2002 June; 48(6 Pt 1): 936-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029012

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Comparing fasting plasma glucose against two-hour post-load glucose concentrations for the diagnosis of diabetes mellitus and glucose intolerance in Singaporean hospital patients. Author(s): Chen YT, Mukherjee JJ, Lee CH, Au VS, Tavintharan S. Source: Ann Acad Med Singapore. 2002 March; 31(2): 189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957556

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Comparison of ADA and WHO criteria for diagnosis of diabetes and glucose intolerance. Author(s): Larsson H, Berglund G, Lindgarde F, Ahren B. Source: Diabetologia. 1998 September; 41(9): 1124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9754834

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Comparison of home glucose monitoring with the oral glucose tolerance test to detect gestational glucose intolerance. Author(s): Peterson KA, Peterson AM, Corbett V, Tongen S, Guzman M, Mazze R. Source: The Journal of Family Practice. 1994 December; 39(6): 558-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798859

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Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals. Author(s): Drzewoski J, Czupryniak L. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 January; 18(1): 29-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168338

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Cortisol metabolism and glucose intolerance. Author(s): Kerstens MN, Dullaart RP. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2951; Author Reply 2951-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788912

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Cross-sectional but not longitudinal associations between non-esterified fatty acid levels and glucose intolerance and other features of the metabolic syndrome. Author(s): Byrne CD, Maison P, Halsall D, Martensz N, Hales CN, Wareham NJ. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1999 December; 16(12): 1007-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656229

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Decline in incidence of epidemic glucose intolerance in Nauruans: implications for the "thrifty genotype". Author(s): Dowse GK, Zimmet PZ, Finch CF, Collins VR. Source: American Journal of Epidemiology. 1991 June 1; 133(11): 1093-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2035513

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Decreased insulin-mediated but not non-insulin-dependent glucose disposal rates in glucose intolerance and type II diabetes in African (Ghanaian) immigrants. Author(s): Osei K, Schuster DP. Source: The American Journal of the Medical Sciences. 1996 March; 311(3): 113-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8615385

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Delineating the relationship between stress, depressive symptoms, and glucose intolerance. Author(s): Grandinetti A, Kaholokula JK, Chang HK. Source: Diabetes Care. 2000 September; 23(9): 1443-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10977057

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Detecting glucose intolerance after gestational diabetes: inadequacy of fasting glucose alone and risk associated with gestational diabetes and second trimester waist-hip ratio. Author(s): Jacob Reichelt AA, Ferraz TM, Rocha Oppermann ML, Costa e Forti A, Duncan BB, Fleck Pessoa E, Schmidt MI. Source: Diabetologia. 2002 March; 45(3): 455-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914756

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Detection of glucose intolerance in pregnancy. Author(s): Mazze RS. Source: Int J Clin Pharmacol Ther Toxicol. 1993 September; 31(9): 440-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225693

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Detection of glucose intolerance in pregnancy. Author(s): Helton DG, Martin RW, Martin JN Jr, Meeks GR, Morrison JC. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 1989 September; 9(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2809777

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Diabetes and glucose intolerance as risk factors for stroke. Author(s): Tuomilehto J, Rastenyte D. Source: Journal of Cardiovascular Risk. 1999 August; 6(4): 241-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10501276

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Diabetes Screening in Canada (DIASCAN) Study: prevalence of undiagnosed diabetes and glucose intolerance in family physician offices. Author(s): Leiter LA, Barr A, Belanger A, Lubin S, Ross SA, Tildesley HD, Fontaine N; Diabetes Screening in Canada (DIASCAN) Study. Source: Diabetes Care. 2001 June; 24(6): 1038-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375367

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Diabetic glomerulosclerosis without glucose intolerance. Author(s): Nash DA Jr, Rogers PW, Langlinais PC, Bunn SM Jr. Source: The American Journal of Medicine. 1975 August; 59(2): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1155478

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Diabetic ketoacidosis in an HIV patient: a new mechanism of HIV protease inhibitorinduced glucose intolerance. Author(s): Kan VL, Nylen ES. Source: Aids (London, England). 1999 October 1; 13(14): 1987-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10513665

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Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Author(s): Puavilai G, Chanprasertyotin S, Sriphrapradaeng A. Source: Diabetes Research and Clinical Practice. 1999 April; 44(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414936

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Diagnostic criteria of glucose intolerance and mortality. Author(s): Qiao Q, Tuomilehto J. Source: Minerva Med. 2001 April; 92(2): 113-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323573

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Diagnostic strategies to detect glucose intolerance in a multiethnic population. Author(s): Anand SS, Razak F, Vuksan V, Gerstein HC, Malmberg K, Yi Q, Teo KK, Yusuf S. Source: Diabetes Care. 2003 February; 26(2): 290-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547851

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Dietary change and obesity associated with glucose intolerance in Alaska Natives. Author(s): Murphy NJ, Schraer CD, Thiele MC, Boyko EJ, Bulkow LR, Doty BJ, Lanier AP. Source: Journal of the American Dietetic Association. 1995 June; 95(6): 676-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7759744

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Dietary patterns and glucose intolerance among aural Indian populations. Author(s): Rao PV. Source: J Indian Med Assoc. 2002 March; 100(3): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408269

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Dietary patterns in a high-risk population for glucose intolerance. Japanese-Brazilian Diabetes Study Group. Author(s): Costa MB, Ferreira SR, Franco LJ, Gimeno SG, Iunes M. Source: J Epidemiol. 2000 March; 10(2): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10778035

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Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance. Author(s): Takahashi H, Matsusawa M, Nishimura M, Nakanishi T, Yoshimura M. Source: Journal of Cardiovascular Pharmacology. 1993; 22 Suppl 2: S22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7508019

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Does maternal glucose intolerance affect the length of gestation in singleton pregnancies? Author(s): Lao TT, Ho LF. Source: Journal of the Society for Gynecologic Investigation. 2003 September; 10(6): 36671. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969780

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Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance. Author(s): Crossey PA, Jones JS, Miell JP. Source: Diabetes. 2000 March; 49(3): 457-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868969

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Effect of 1,25 (OH)2D3 treatment on glucose intolerance in uraemia. Author(s): Turk S, Yeksan M, Tamer N, Gurbilek M, Erdogan Y, Erkul I. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1992; 7(12): 1207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1337161

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Effect of acarbose on glucose intolerance in patients with non-insulin-dependent diabetes mellitus. Author(s): Noda K, Umeda F, Nawata H. Source: Diabetes Research and Clinical Practice. 1997 August; 37(2): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9279483

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Effect of habitual physical activity on age-related glucose intolerance. Author(s): Wang JT, Ho LT, Tang KT, Wang LM, Chen YD, Reaven GM. Source: Journal of the American Geriatrics Society. 1989 March; 37(3): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2645353

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Effect of macronutrient intake on the development of glucose intolerance during pregnancy. Author(s): Saldana TM, Siega-Riz AM, Adair LS. Source: The American Journal of Clinical Nutrition. 2004 March; 79(3): 479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985225

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Effect of overweight and obesity on glucose intolerance and dyslipidemia in Saudi Arabia, epidemiological study. Author(s): Rahman Al-Nuaim A. Source: Diabetes Research and Clinical Practice. 1997 June; 36(3): 181-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9237785

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Effect of past and concurrent body mass index on prevalence of glucose intolerance and type 2 (non-insulin-dependent) diabetes and on insulin response. The Israel study of glucose intolerance, obesity and hypertension. Author(s): Modan M, Karasik A, Halkin H, Fuchs Z, Lusky A, Shitrit A, Modan B. Source: Diabetologia. 1986 February; 29(2): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3516770

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Effect of physical activity on age-related glucose intolerance. Author(s): Laws A, Reaven GM. Source: Clinics in Geriatric Medicine. 1990 November; 6(4): 849-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2224751

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Effects of heparin-induced non-esterified free fatty acid on minimal model-derived insulin sensitivity in individuals with varying degrees of glucose intolerance. Author(s): Osei K, Schuster DP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1995 October; 12(10): 911-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846683

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Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in women with gestational diabetes. Author(s): Conway DL, Langer O. Source: American Journal of Obstetrics and Gynecology. 1999 September; 181(3): 610-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10486471

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Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men. Author(s): Bolinder J, Lithell H, Skarfors E, Arner P. Source: Diabetes. 1986 March; 35(3): 282-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3512339

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Effects of perindopril on glucose and lipid metabolism in patients with mild-tomoderate essential hypertension and glucose intolerance. Author(s): Uchida K, Azukizawa S, Kigoshi T, Nakano S, Kaneko M, Morimoto S, Matsui A. Source: Clinical Therapeutics. 1994 May-June; 16(3): 466-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7923313

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Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Author(s): Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims EA. Source: Diabetes. 1984 April; 33(4): 311-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6368289

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Effects of very low calorie diet (VLCD) on body weight, blood glucose and serum lipid metabolism in severe obesity with glucose intolerance. Author(s): Inoue S, Okamura A, Okamoto M, Tanaka K, Sugimasa T, Takamura Y. Source: Int J Obes. 1989; 13 Suppl 2: 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2613422

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Epidemiology of glucose intolerance and associated factors in Uzbekistan: a survey in Sirdaria province. Author(s): King H, Djumaeva S, Abdullaev B, Gacic Dobo M. Source: Diabetes Research and Clinical Practice. 2002 January; 55(1): 19-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755475

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Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age. Author(s): King H. Source: Diabetes Care. 1998 August; 21 Suppl 2: B9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704221

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Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria. Author(s): Buzzelli G, Chiarantini E, Cotrozzi G, Relli P, Matassi L, Romanelli RG, Gentilini P. Source: Liver. 1988 December; 8(6): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3265171

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Estimated prevalence of undiagnosed glucose intolerance from hyperandrogenic anovulation among women requesting electrolysis. Author(s): Dumesic DA, Herrmann RR, O'Brien AM. Source: Int J Fertil Womens Med. 1997 July-August; 42(4): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9309459

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Evaluation of glucose intolerance in pregnancy using biochemical markers of fetal hyperinsulinemia. Author(s): Roach VJ, Fung H, Cockram CS, Lau TK, Rogers MS. Source: Gynecologic and Obstetric Investigation. 1998; 45(3): 174-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565141

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Evaluation of insulin release and relative peripheral resistance with use of the oral glucose tolerance test: a study in subjects with normoglycaemia, glucose intolerance and non-insulin-dependent diabetes mellitus. Author(s): Cederholm J, Wibell L. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1985 December; 45(8): 741-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3909372

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Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging. Author(s): Kahn SE, Larson VG, Schwartz RS, Beard JC, Cain KC, Fellingham GW, Stratton JR, Cerqueira MD, Abrass IB. Source: The Journal of Clinical Endocrinology and Metabolism. 1992 June; 74(6): 1336-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1592879

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Factors influencing the development of glucose intolerance in Cushing syndrome. Author(s): Scand J Gastroenterol. 1995 Dec;30(12):1228 Source: Acta Medica Austriaca. 1995; 22(5): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9053980

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Familial glucose-galactose malabsorption: remission of glucose intolerance. Author(s): Elsas LJ 2nd, Lambe DW Jr. Source: The Journal of Pediatrics. 1973 August; 83(2): 226-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4717580

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Fasting blood sugar level: a determinant for in-hospital outcome in patients with first myocardial infarction and without glucose intolerance. Author(s): Mak KH, Mah PK, Tey BH, Sin FL, Chia G. Source: Ann Acad Med Singapore. 1993 May; 22(3): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8373106

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Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study. Author(s): Salomaa V, Ahola I, Tuomilehto J, Aro A, Pietinen P, Korhonen HJ, Penttila I. Source: Metabolism: Clinical and Experimental. 1990 December; 39(12): 1285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2246969

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Fetal loss and maternal glucose intolerance. A retrospective study. Author(s): Sutherland HW, Fisher PM. Source: Padiatr Padol. 1982; 17(2): 279-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7099681

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First-phase insulin response to glucose in nonobese or obese subjects with glucose intolerance: analysis by C-peptide secretion rate. Author(s): Kanatsuka A, Makino H, Sakurada M, Hashimoto N, Iwaoka H, Yamaguchi T, Taira M, Yoshida S, Yoshida A. Source: Metabolism: Clinical and Experimental. 1988 September; 37(9): 878-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3047522

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Frequency of occurrence and interpretation of glucose intolerance in patients with Addison's disease. Author(s): Vandeput Y, Buysschaert M, Irvine WJ, Crabbe J. Source: Annales D'endocrinologie. 1980 May-June; 41(3): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7416714

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Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance. Author(s): Bonora E, Zavaroni I, Manicardi V, Coscelli C, Butturini U. Source: J Endocrinol Invest. 1986 October; 9(5): 371-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3540080

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Further support for heterogeneity of insulin response and insulin sensitivity in nonobese subjects with glucose intolerance. Author(s): Ratzmann KP, Witt S, Schulz B. Source: Acta Endocrinol (Copenh). 1983 March; 102(3): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6338676

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Future glucose intolerance possibly manifest in youth. Author(s): King H, Alpers M, Finch C, Zimmet P. Source: Lancet. 1989 November 4; 2(8671): 1098-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2572818

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Glucose intolerance after massive liver resection in man and other mammals. Author(s): Ida T, Ozawa K, Honjo I. Source: American Journal of Surgery. 1975 May; 129(5): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1130591

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Glucose intolerance and aging. Author(s): DeFronzo RA. Source: Diabetes Care. 1981 July-August; 4(4): 493-501. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7049632

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Glucose intolerance and aging: evidence for tissue insensitivity to insulin. Author(s): Defronzo RA. Source: Diabetes. 1979 December; 28(12): 1095-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=510806

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Glucose intolerance and insulin resistance in aplastic anemia treated with oxymetholone. Author(s): Woodard TL, Burghen GA, Kitabchi AE, Wilimas JA. Source: The Journal of Clinical Endocrinology and Metabolism. 1981 November; 53(5): 905-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7026595

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Glucose intolerance associated with temporomandibular joint pain-dysfunction syndrome. Author(s): Oles RD. Source: Oral Surg Oral Med Oral Pathol. 1977 April; 43(4): 546-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=265482

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Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Author(s): Duckworth WC, Solomon SS, Jallepalli P, Heckemeyer C, Finnern J, Powers A. Source: Diabetes. 1980 November; 29(11): 906-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7429029

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Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly. Author(s): Amery A, Berthaux P, Bulpitt C, Deruyttere M, de Schaepdryver A, Dollery C, Fagard R, Forette F, Hellemans J, Lund-Johansen P, Mutsers A, Tuomilehto J. Source: Lancet. 1978 April 1; 1(8066): 681-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=76223

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Glucose intolerance during pregnancy. I. A reappraisal of alleged screening criteria. Author(s): Granat M, Sharf M, Cooper A. Source: Obstetrics and Gynecology. 1979 February; 53(2): 157-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=418967

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Glucose intolerance during pregnancy. II. A comparative study of diagnostic screening methods. Author(s): Cooper A, Granat M, Sharf M. Source: Obstetrics and Gynecology. 1979 April; 53(4): 495-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=440654

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Glucose intolerance following chronic metabolic acidosis in man. Author(s): DeFronzo RA, Beckles AD. Source: The American Journal of Physiology. 1979 April; 236(4): E328-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=434194

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Glucose intolerance in alcoholism. Author(s): Sereny G, Endrenyi L, Devenyi P. Source: J Stud Alcohol. 1975 March; 36(3): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=235678

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Glucose intolerance in hyperthyroidism: role of glucagon. Author(s): Kabadi UM, Eisenstein AB. Source: The Journal of Clinical Endocrinology and Metabolism. 1980 February; 50(2): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6986398

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Glucose intolerance in Parkinson's disease. Author(s): Lipman IJ, Boykin ME, Flora RE. Source: J Chronic Dis. 1974 December; 27(11-12): 573-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4436423

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Glucose intolerance in the carcinoid syndrome. Author(s): Feldman JM, Plonk JW, Bivens CH, Lebovitz HE. Source: Diabetes. 1975 July; 24(7): 664-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=125668

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Glucose intolerance in the hemodialyzed patient: a brief overview. Author(s): Westervelt FB Jr. Source: Kidney International. Supplement. 1974 October; (1): 70-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4619140

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Glucose intolerance in uremia (A- and B-cell function during conservative and dialytic management. Author(s): Benedetti MM, Santeusanio F, Angeletti G, Filipponi P, Buoncristiani U, Brunetti P. Source: Acta Diabetol Lat. 1977 September-December; 14(5-6): 235-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=613688

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Glucose intolerance in uremia. Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin. Author(s): DeFronzo RA, Tobin JD, Rowe JW, Andres R. Source: The Journal of Clinical Investigation. 1978 August; 62(2): 425-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=353075

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Glucose intolerance in uremia: site and mechanism. Author(s): DeFronzo RA, Alvestrand A. Source: The American Journal of Clinical Nutrition. 1980 July; 33(7): 1438-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6994471

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Glucose intolerance, diabetes mellitus and atherosclerosis; prospects for prevention. Author(s): Keen H. Source: Postgraduate Medical Journal. 1976 July; 52(609): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=967763

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Glycohemoglobin. Its use in the follow-up of diabetes and diagnosis of glucose intolerance. Author(s): Lev-Ran A. Source: Archives of Internal Medicine. 1981 May; 141(6): 747-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7235783

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Healthy diet and lifestyle clustering and glucose intolerance. Author(s): Perry IJ. Source: The Proceedings of the Nutrition Society. 2002 November; 61(4): 543-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691184

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Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes. Author(s): Koenig RJ, Peterson CM, Kilo C, Cerami A, Williamson JR. Source: Diabetes. 1976 March; 25(3): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1254113

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Hepatic dearterialisation induces glucose intolerance and inhibits insulin secretion in patients with liver malignancy. Author(s): Sjovall S, Ahren B. Source: The European Journal of Surgery = Acta Chirurgica. 1991 May; 157(5): 329-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678646

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High glycosylated hemoglobin levels increase the risk of progression to diabetes mellitus in subjects with glucose intolerance. Author(s): Yoshinaga H, Kosaka K. Source: Diabetes Research and Clinical Practice. 1996 March; 31(1-3): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792104

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High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease. Author(s): Yawata N, Nakamura S, Kijima M, Ikai N, Kanai M, Sugita M, Ohno S. Source: The British Journal of Ophthalmology. 1999 January; 83(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209432

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HLA type, islet cell antibodies, and glucose intolerance in cystic fibrosis. Author(s): Stutchfield PR, O'Halloran SM, Smith CS, Woodrow JC, Bottazzo GF, Heaf D. Source: Archives of Disease in Childhood. 1988 October; 63(10): 1234-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3058046

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Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population. Author(s): Harris MI. Source: Diabetes Care. 1991 May; 14(5): 366-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2060448

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Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance. Author(s): Shiraishi I, Iwamoto Y, Kuzuya T, Matsuda A, Kumakura S. Source: Diabetologia. 1991 October; 34(10): 737-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1959706

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Hyperinsulinemia in glucose intolerance: is it true? Author(s): Giugliano D, Quatraro A, Acampora R, De Rosa N, Ceriello A, D'Onofrio F. Source: J Endocrinol Invest. 1994 June; 17(6): 391-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7930385

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Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. Author(s): Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Source: The Journal of Clinical Investigation. 1985 March; 75(3): 809-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3884667

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Hyperinsulinemia--a link between glucose intolerance, obesity, hypertension, dyslipoproteinemia, elevated serum uric acid and internal cation imbalance. Author(s): Modan M, Halkin H, Fuchs Z, Lusky A, Chetrit A, Segal P, Eshkol A, Almog S, Shefi M. Source: Diabete Metab. 1987 July; 13(3 Pt 2): 375-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3308568

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Hyperlipidemia and glucose intolerance in the post-renal transplant patient. Author(s): Markell MS, Armenti V, Danovitch G, Sumrani N. Source: Journal of the American Society of Nephrology : Jasn. 1994 February; 4(8 Suppl): S37-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8193294

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Hypertension and pre-eclampsia in women with gestational glucose intolerance. Author(s): Suhonen L, Teramo K. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1993 May; 72(4): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8389513

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Hypertension in Alaska Natives: association with overweight, glucose intolerance, diet and mechanized activity. Author(s): Murphy NJ, Schraer CD, Theile MC, Boyko EJ, Bulkow LR, Doty BJ, Lanier AP. Source: Ethnicity & Health. 1997 November; 2(4): 267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9526689

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Hypertension in glucose intolerance and diabetes. Author(s): Jarrett RJ. Source: Journal of Internal Medicine. Supplement. 1991; 735: 85-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2043226

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Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance. Author(s): Verza M, D'Avino M, Cacciapuoti F, Aceto E, D'Errico S, Varricchio M, Giugliano D. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1988 November; 6(1): S45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3063793

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Hyperthyroidism and glucose intolerance. Author(s): Ahren B. Source: Acta Med Scand. 1986; 220(1): 5-14. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3532696

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Hypertriglyceridemia in different degrees of glucose intolerance in a Finnish population-based study. Author(s): Salomaa VV, Tuomilehto J, Jauhiainen M, Korhonen HJ, Stengard J, Uusitupa M, Pitkanen M, Penttila I. Source: Diabetes Care. 1992 May; 15(5): 657-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1516486

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Hypokalemia, glucose intolerance, and hyperinsulinemia during diuretic therapy. Author(s): Plavinik FL, Rodrigues CI, Zanella MT, Ribeiro AB. Source: Hypertension. 1992 February; 19(2 Suppl): Ii26-9. Erratum In: Hypertension 1992 August; 20(2): 265. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1735589

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Hypophosphatemia and glucose intolerance: evidence for tissue insensitivity to insulin. Author(s): DeFronzo RA, Lang R. Source: The New England Journal of Medicine. 1980 November 27; 303(22): 1259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6999353

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Immunosuppression in renal transplantation. Postoperative glucose intolerance was almost certainly underestimated. Author(s): Krentz AJ. Source: Bmj (Clinical Research Ed.). 1999 October 23; 319(7217): 1136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10610150

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Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Author(s): Rutter MK, Parise H, Benjamin EJ, Levy D, Larson MG, Meigs JB, Nesto RW, Wilson PW, Vasan RS. Source: Circulation. 2003 January 28; 107(3): 448-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12551870

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Impact of the 1997 American Diabetes Association criteria on classification of glucose intolerance among Kuwaitis below 50 years of age. Author(s): Abdella N, Al Nakhi A, Al Arouj M, Assoussi A, Moussa M. Source: Acta Diabetologica. 1999 September; 36(3): 133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10664317

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Impaired ('diabetic') insulin signaling and action occur in fat cells long before glucose intolerance--is insulin resistance initiated in the adipose tissue? Author(s): Smith U. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 July; 26(7): 897-904. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12080441

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Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance. Author(s): Ahren B, Pacini G. Source: The American Journal of Physiology. 1997 October; 273(4 Pt 1): E701-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9357798

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Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance. Author(s): Ebert R, Frerichs H, Creutzfeldt W. Source: European Journal of Clinical Investigation. 1979 April; 9(2 Pt 1): 129-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=111943

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Increased glucose intolerance related to digoxin treatment in patients with type 2 diabetes mellitus. Author(s): Spigset O, Mjorndal T. Source: Journal of Internal Medicine. 1999 October; 246(4): 419-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10583713

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Increased risk factors for coronary artery disease in Japanese subjects with hyperinsulinemia or glucose intolerance. Author(s): Yamada N, Yoshinaga H, Sakurai N, Shimano H, Gotoda T, Ohashi Y, Yazaki Y, Kosaka K. Source: Diabetes Care. 1994 February; 17(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8137680

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Influences of increased oxidative stress on endothelial function, platelets function, and fibrinolysis in hypertension associated with glucose intolerance. Author(s): Tomiyama H, Kushiro T, Okazaki R, Yoshida H, Doba N, Yamashina A. Source: Hypertens Res. 2003 April; 26(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733697

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Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). Author(s): Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS. Source: The Journal of Clinical Investigation. 2003 February; 111(4): 453-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588883

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Insulin levels and the natural history of glucose intolerance in Nauruans. Author(s): Dowse GK, Zimmet PZ, Collins VR. Source: Diabetes. 1996 October; 45(10): 1367-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826973

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Insulin release, insulin sensitivity, and glucose intolerance. Author(s): Efendic S, Wajngot A, Cerasi E, Luft R. Source: Proceedings of the National Academy of Sciences of the United States of America. 1980 December; 77(12): 7425-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7012840

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Insulin resistance, glucose intolerance, and hyperinsulinemia in patients with microvascular angina. Author(s): Fuh MM, Jeng CY, Young MM, Sheu WH, Chen YD, Reaven GM. Source: Metabolism: Clinical and Experimental. 1993 September; 42(9): 1090-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412759

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Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia. Author(s): Sheu WH, Shieh SM, Fuh MM, Shen DD, Jeng CY, Chen YD, Reaven GM. Source: Arterioscler Thromb. 1993 March; 13(3): 367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8443140

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Insulin resistance, glucose intolerance, hyperinsulinemia and dyslipidemia in patients with angiographically demonstrated coronary artery disease. Author(s): Young MH, Jeng CY, Sheu WH, Shieh SM, Fuh MM, Chen YD, Reaven GM. Source: The American Journal of Cardiology. 1993 August 15; 72(5): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8352190

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Insulin response to glucose and tolbutamide in "essential" versus "pancreatic" mild glucose intolerance. Author(s): Vague P, Ramahandridona G, Gerolami A. Source: Diabetes. 1974 November; 23(11): 896-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4430416

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Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes. Author(s): Kosaka K, Hagura R, Kuzuya T. Source: Diabetes. 1977 October; 26(10): 944-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=908463

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Insulin secretory responses in patients with glucose intolerance due to extrapancreatic causes. Comparison with idiopathic diabetes mellitus. Author(s): Kosaka K, Kuzuya T, Hagura R, Akanuma Y, Kanazawa Y. Source: Endocrinol Jpn. 1981 August; 28(4): 487-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6763894

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Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. Author(s): Cavaghan MK, Ehrmann DA, Polonsky KS. Source: The Journal of Clinical Investigation. 2000 August; 106(3): 329-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10930434

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Internalized racism is associated with glucose intolerance among Black Americans in the U.S. Virgin Islands. Author(s): Tull ES, Chambers EC. Source: Diabetes Care. 2001 August; 24(8): 1498. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11473095

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Letter: Glucose intolerance and diuretics. Author(s): Ram CV. Source: Lancet. 1976 May 29; 1(7970): 1186. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=58231

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Letter: Glucose intolerance and peripheral glucose uptake in acutely intoxicated alcoholics. Author(s): Eriksson CE, Hed R, Lindblad LE, Nygren A, Sundblad L. Source: Lancet. 1974 April 27; 1(7861): 811-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4132746

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Letter: Glucose intolerance in pulmonary. Author(s): Nichols GP. Source: Am Rev Respir Dis. 1974 September; 110(3): 368. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4414239

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Letter: Pyridoxine and oestrogen-induced glucose intolerance. Author(s): Cornish EJ, Tesoriero W. Source: British Medical Journal. 1975 September 13; 3(5984): 649-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1164654

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Limitations of glycosylated haemoglobin as an index of glucose intolerance. Author(s): Snehalatha C, Ramachandran A, Satyavani K, Vijay V. Source: Diabetes Research and Clinical Practice. 2000 February; 47(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10670913

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Limited insulin responses in older non-obese control subjects without glucose intolerance. Author(s): Corredor DG, Jung Y, Khurana RC, Creech R, Christy W, Nealis T, Danowski TS. Source: Pol Med Sci Hist Bull. 1971 January; 14(1): 13-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5100384

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Lipids, glucose intolerance and vascular disease: the Framingham Study. Author(s): Wilson PW, Kannel WB, Anderson KM. Source: Monogr Atheroscler. 1985; 13: 1-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4088270

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Lipoprotein response to exercise training and a low-fat diet in older subjects with glucose intolerance. Author(s): Hughes VA, Fiatarone MA, Ferrara CM, McNamara JR, Charnley JM, Evans WJ. Source: The American Journal of Clinical Nutrition. 1994 April; 59(4): 820-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8147325

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Lipoprotein(a) levels in hemodialysis patients: relation to glucose intolerance and hemodialysis duration. Author(s): Fiorini F, Masturzo P, Mij M, Bertolini S. Source: Nephron. 1995; 70(4): 500-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7477660

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Lithium carbonate-induced nephrogenic diabetes insipidus and glucose intolerance. Author(s): Martinez-Maldonado M, Terrell J. Source: Archives of Internal Medicine. 1973 December; 132(6): 881-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4757260

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Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance. Author(s): Swinburn BA, Metcalf PA, Ley SJ. Source: Diabetes Care. 2001 April; 24(4): 619-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315819

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Long-term effects of fluoxetine on glycemic control in obese patients with noninsulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. Author(s): Breum L, Bjerre U, Bak JF, Jacobsen S, Astrup A. Source: Metabolism: Clinical and Experimental. 1995 December; 44(12): 1570-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786726

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Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Author(s): Tanko LB, Bagger YZ, Christiansen C. Source: Cancer. 2004 June 15; 100(12): 2680-1; Author Reply 2681. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15197812

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Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Author(s): Dawson SI. Source: Cancer. 2004 January 1; 100(1): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692035

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Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle-aged men. Author(s): Carlsson S, Persson PG, Alvarsson M, Efendic S, Norman A, Svanstrom L, Ostenson CG, Grill V. Source: Diabetes Care. 1999 July; 22(7): 1043-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388964

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Making things easier is not so easy. The 1997 American Diabetes Association criteria and glucose intolerance. Author(s): Aguilar-Salinas CA, Garcia-Garcia E, Lerman-Garber I, Gomez-Perez FJ, Rull JA. Source: Diabetes Care. 1998 June; 21(6): 1027-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614628

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Maternal ante-natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro-Caribbeans, Asians and Caucasians. Author(s): Sinha B, Brydon P, Taylor RS, Hollins A, Munro A, Jenkins D, Dunne F. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 May; 20(5): 382-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752487

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Maternal fructosamine and glycosylated haemoglobin in the prediction of gestational glucose intolerance. Author(s): Aziz NL, Abdelwahab S, Moussa M, Georgy M. Source: Clin Exp Obstet Gynecol. 1992; 19(4): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1294344

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Maternal glucose intolerance and the subcutaneous terbutaline pump. Author(s): Lindenbaum C, Ludmir J, Teplick FB, Cohen AW, Samuels P. Source: American Journal of Obstetrics and Gynecology. 1992 March; 166(3): 925-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1550166

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Maternal obesity and glucose intolerance during pregnancy among MexicanAmericans. Author(s): Kieffer EC. Source: Paediatric and Perinatal Epidemiology. 2000 January; 14(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703030

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Mechanism of glucose intolerance during fasting: differences between lean and obese subjects. Author(s): Goschke H. Source: Metabolism: Clinical and Experimental. 1977 October; 26(10): 1147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=895529

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Mechanism of glucose intolerance in cystic fibrosis. Author(s): Clodi HP, Pfeiffer EF. Source: The New England Journal of Medicine. 1970 February 19; 282(8): 455-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5412202

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Mechanisms associating body fat distribution to glucose intolerance and diabetes mellitus: window with a view. Author(s): Kissebah AH, Peiris AN, Evans DJ. Source: Acta Med Scand Suppl. 1988; 723: 79-89. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3293360

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Mechanisms of epinephrine-induced glucose intolerance in normal humans. Author(s): Sacca L, Vigorito C, Cicala M, Ungaro B, Sherwin RS. Source: The Journal of Clinical Investigation. 1982 February; 69(2): 284-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7035494

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Mechanisms of glucose intolerance during triglyceride infusion. Author(s): Rigalleau V, Beylot M, Pachiaudi C, Guillot C, Deleris G, Gin H. Source: The American Journal of Physiology. 1998 October; 275(4 Pt 1): E641-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755083

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Medical pathology conference. A 54-year-old man with progressive glucose intolerance. Author(s): Garcia JH, Reynertson R, Breatnach E, Herrera GA. Source: Ala J Med Sci. 1985 July; 22(3): 281-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2992306

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Metabolic disturbances increasing the risk of coronary heart disease during diureticbased antihypertensive therapy: lipid alterations and glucose intolerance. Author(s): Ames RP. Source: American Heart Journal. 1983 November; 106(5 Pt 2): 1207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6637786

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Metabolic effects of physical training in subjects with oral glucose intolerance. Author(s): Erle G, Cortesi S, Zen F, Mingardi R, Sicolo N. Source: International Journal of Sports Medicine. 1985 October; 6(5): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4055193

76

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More on thyroid status in patients with chronic renal failure: effect of glucose intolerance on serum reverse T3. Author(s): De Marchi S, Cecchin E, Tesio F, Borean M. Source: Clinical Nephrology. 1984 May; 21(5): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6734000

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Natural history of glucose intolerance in obesity. A ten year observation. Author(s): Toeller M, Gries FA, Dannehl K. Source: Int J Obes. 1982; 6 Suppl 1: 145-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6749720

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Neonatal morbidities in infants of mothers with glucose intolerance in pregnancy. Author(s): Widness JA, Cowett RM, Coustan DR, Carpenter MW, Oh W. Source: Diabetes. 1985 June; 34 Suppl 2: 61-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3996769

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Nifedipine vs. enalapril in treatment of hypertensive patients with glucose intolerance. Author(s): Andronico G, Piazza G, Mangano MT, Mule G, Carone MB, Cerasola G. Source: Journal of Cardiovascular Pharmacology. 1991; 18 Suppl 10: S52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1725004

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Nitrogen utilization, enzyme activity, glucose intolerance and leukocyte chemotaxis in human experimental zinc depletion. Author(s): Baer MT, King JC, Tamura T, Margen S, Bradfield RB, Weston WL, Daugherty NA. Source: The American Journal of Clinical Nutrition. 1985 June; 41(6): 1220-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3890515

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Nodular glomerulosclerosis without glucose intolerance: long-term follow-up. Author(s): Gonzalo A, Navarro J, Mampaso F, Ortuno J. Source: Nephron. 1994; 66(4): 481-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8015658

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Non-insulin-dependent diabetes mellitus, glucose intolerance, blood pressure, hypertension, and antihypertensive drugs. Author(s): Jarrett RJ, Fitzgerald AP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1994 AugustSeptember; 11(7): 646-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7955988

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Obesity, glucose intolerance and diabetes and their links to cardiovascular disease. Implications for laboratory medicine. Author(s): Dominiczak MH. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 September; 41(9): 1266-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598880

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Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Author(s): Modan M, Almog S, Fuchs Z, Chetrit A, Lusky A, Halkin H. Source: Hypertension. 1991 April; 17(4): 565-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2013483

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Obesity, lipids, and glucose intolerance. The Framingham Study. Author(s): Kannel WB, Gordon T, Castelli WP. Source: The American Journal of Clinical Nutrition. 1979 June; 32(6): 1238-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=443188

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Obesity, very low density lipoproteins, and glucose intolerance over fourteen years: The Framingham Study. Author(s): Wilson PW, McGee DL, Kannel WB. Source: American Journal of Epidemiology. 1981 November; 114(5): 697-704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7304597

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Occult glucose intolerance: incidence in a general population. Author(s): Searcy RL, Low EM. Source: Calif Med. 1967 May; 106(5): 364-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6046045

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Occurrence of intercapillary nodular glomerulosclerosis in the absence of glucose intolerance. Author(s): Kanwar YS, Garces J, Molitch ME. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1990 March; 15(3): 281-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2407111

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Office guide to diagnosis and classification of diabetes mellitus and other categories of glucose intolerance. Author(s): Shuman CR, Spratt IL. Source: Diabetes Care. 1981 March-April; 4(2): 335. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7215090

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On the role of islet amyloid polypeptide in glucose intolerance and anorexia of pancreatic cancer. Author(s): Herrington MK, Arnelo U, Permert J. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(3): 267-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12120206

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Oral contraceptive use: prospective follow-up of women with suspected glucose intolerance. Author(s): Duffy TJ, Ray R. Source: Contraception. 1984 September; 30(3): 197-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6509976

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Outcome of diabetic pregnancy and glucose intolerance in pregnancy: an audit of fetal loss in Newcastle General Hospital 1977-1990. Author(s): Hawthorne G, Snodgrass A, Tunbridge M. Source: Diabetes Research and Clinical Practice. 1994 October; 25(3): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7851273

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Pakistan National Diabetes Survey prevalence of glucose intolerance and associated factors in North West at Frontier Province (NWFP) of Pakistan. Author(s): Shera AS, Rafique G, Khwaja IA, Baqai S, Khan IA, King H, Ahmed KI. Source: J Pak Med Assoc. 1999 September; 49(9): 206-11. Erratum In: Jpma J Pak Med Assoc 1999 December; 49(12): 317. Ahmed Ki[corrected to Khwaja Ia]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10646320

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Pakistan National Diabetes Survey: prevalence of glucose intolerance and associated factors in Baluchistan province. Author(s): Shera AS, Rafique G, Khawaja IA, Baqai S, King H. Source: Diabetes Research and Clinical Practice. 1999 April; 44(1): 49-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414940

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Parallel changes of proinsulin and islet amyloid polypeptide in glucose intolerance. Author(s): MacNamara CM, Barrow BA, Manley SE, Levy JC, Clark A, Turner RC. Source: Diabetes Research and Clinical Practice. 2000 October; 50(2): 117-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960722

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Pathogenesis of glucose intolerance in uremia. Author(s): DeFronzo RA. Source: Metabolism: Clinical and Experimental. 1978 December; 27(12 Suppl 2): 1866-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=723638

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Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes. Author(s): Kobayashi K, Amemiya S, Higashida K, Ishihara T, Sawanobori E, Kobayashi K, Mochizuki M, Kikuchi N, Tokuyama K, Nakazawa S. Source: Metabolism: Clinical and Experimental. 2000 February; 49(2): 186-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10690942

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Patterns of glucose intolerance and free fatty acid behavior in viral hepatitis. Author(s): Granot C, Bar-On H, Shafrir E. Source: Isr J Med Sci. 1981 January; 17(1): 12-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7007283

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PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Author(s): Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, Watarai T, Umayahara Y, Matsuhisa M, Gorogawa S, Kuwayama Y, Tano Y, Yamasaki Y, Hori M. Source: Diabetes. 2002 January; 51(1): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756345

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Perinatal significance of diagnosing glucose intolerance during pregnancy with portable glucose meter. Author(s): Jakobi P, Weissman A, Egozi J, Minuchin O, Geva A. Source: Journal of Perinatal Medicine. 2003; 31(2): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747230

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Peripheral neuropathy in myotonic dystrophy. Relation to glucose intolerance. Author(s): Olson ND, Jou MF, Quast JE, Nuttall FQ. Source: Archives of Neurology. 1978 November; 35(11): 741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=718472

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Placental weight to birthweight ratio is increased in mild gestational glucose intolerance. Author(s): Lao TT, Lee CP, Wong WM. Source: Placenta. 1997 March-April; 18(2-3): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9089786

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Plasma insulin; insulin resistance and glucose intolerance in children with bilharzial hepatic fibrosis. Author(s): Zaki K, Kantoosh M, Hamam MA, Shoheib S, Mikhail N, Nour H, Zaki F. Source: Hepatogastroenterology. 1980 December; 27(6): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7009363

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Postpartum glucose intolerance in Chinese women with gestational diabetes. Author(s): Yang X, Hsu-Hage BH, Dong L, Zhang H, Zhang C, Zhang Y. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 687-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873301

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Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation. Author(s): Bottini E, Lucarelli P, Amante A, Saccucci P, Gloria-Bottini F. Source: Metabolism: Clinical and Experimental. 2002 January; 51(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782864

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Prevalence and concomitants of glucose intolerance in European obese children and adolescents. Author(s): Invitti C, Guzzaloni G, Gilardini L, Morabito F, Viberti G. Source: Diabetes Care. 2003 January; 26(1): 118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502667

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Prevalence and determinants of diabetes mellitus and glucose intolerance in a Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO criteria. The Guia Study. Author(s): de Pablos-Velasco PL, Martinez-Martin FJ, Rodriguez-Perez F, Ania BJ, Losada A, Betancor P; Guia Study. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 March; 18(3): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318846

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Prevalence of diabetes and glucose intolerance in 199 offspring of thirty-seven conjugal diabetic parents. Author(s): Tattersal RB, Fajans SS. Source: Diabetes. 1975 May; 24(5): 452-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1126589

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Prevalence of glucose intolerance among Malays in Brunei. Author(s): van Eekelen A, Stokvis-Brantsma H, Frolich M, Smelt AH, Stokvis H. Source: Diabetes Care. 2000 September; 23(9): 1435-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10977050

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Prevalence of glucose intolerance among Native Hawaiians in two rural communities. Native Hawaiian Health Research (NHHR) Project. Author(s): Grandinetti A, Chang HK, Mau MK, Curb JD, Kinney EK, Sagum R, Arakaki RF. Source: Diabetes Care. 1998 April; 21(4): 549-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571341

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Prevalence of glucose intolerance in urban and rural communities in Saudi Arabia. Author(s): Al-Nuaim AR. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1997 July; 14(7): 595-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9223399

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Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. Author(s): Rennert NJ, Charney P. Source: Primary Care. 2003 September; 30(3): 569-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692202

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QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen Elderly Study. Author(s): Dekker JM, Feskens EJ, Schouten EG, Klootwijk P, Pool J, Kromhout D. Source: Diabetes. 1996 March; 45(3): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8593946

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Re: "Weight history, glucose intolerance, and insulin levels in middle-aged Swedish men". Author(s): Longnecker MP, Michalek JE. Source: American Journal of Epidemiology. 1999 August 15; 150(4): 430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453822

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Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion. Author(s): Yamamoto K, Miyagawa J, Waguri M, Sasada R, Igarashi K, Li M, Nammo T, Moriwaki M, Imagawa A, Yamagata K, Nakajima H, Namba M, Tochino Y, Hanafusa T, Matsuzawa Y. Source: Diabetes. 2000 December; 49(12): 2021-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11118003

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Reduced glucose effectiveness as a feature of glucose intolerance: evidence in elderly type-2 diabetic subjects. Author(s): Viviani GL, Pacini G. Source: Aging (Milano). 1999 June; 11(3): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10476312

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Rehydration of moderately dehydrated children with transient glucose intolerance using rice oral rehydration solution. Author(s): Yurdakok K, Ozmert E, Yalcin SS, Coskun T. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 January; 88(1): 34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10090544

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Rehydration of two patients with secondary glucose intolerance by using rice-oral rehydration solution (R-ORS) Author(s): Yurdakok K, Ozmert E. Source: Journal of Pediatric Gastroenterology and Nutrition. 1996 November; 23(4): 50910. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8956201

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Relation of high blood pressure to glucose intolerance, plasma lipids and educational status in an Arabian Gulf population. Author(s): Al-Mahroos F, Al-Roomi K, McKeigue PM. Source: International Journal of Epidemiology. 2000 February; 29(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10750606

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Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia. Author(s): Katsuya T, Horiuchi M, Chen YD, Koike G, Pratt RE, Dzau VJ, Reaven GM. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 June; 15(6): 779-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7773733

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Relationship between height, glucose intolerance, and hypertension in an urban African black adult population: a case for the "thrifty phenotype" hypothesis? Author(s): Olatunbosun ST, Bella AF. Source: Journal of the National Medical Association. 2000 June; 92(6): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10918760

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Relationship of glucose intolerance to coronary risk in Afro-Caribbeans compared with Europeans. Author(s): Chaturvedi N, McKeigue PM, Marmot MG. Source: Diabetologia. 1994 August; 37(8): 765-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7988778

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Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM. Author(s): Huang XH, Rantalaiho V, Wirta O, Pasternack A, Koivula T, Hiltunen T, Nikkari T, Lehtimaki T. Source: Human Genetics. 1998 March; 102(3): 372-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9544854

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Relationships between maternal glucose intolerance and neonatal blood glucose. Author(s): Haworth JC, Dilling LA. Source: The Journal of Pediatrics. 1976 November; 89(5): 810-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=978332

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Relative importance of maternal constitutional factors and glucose intolerance of pregnancy in the development of newborn macrosomia. Author(s): Okun N, Verma A, Mitchell BF, Flowerdew G. Source: The Journal of Maternal-Fetal Medicine. 1997 September-October; 6(5): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360188

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Reproducibility of hemoglobin AIc and sensitivity to various degrees of glucose intolerance. Author(s): Dunn PJ, Cole RA, Soeldner JS, Gleason RE. Source: Annals of Internal Medicine. 1979 September; 91(3): 390-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=475166

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Reversal of diet-induced glucose intolerance by hepatic expression of a variant glycogen-targeting subunit of protein phosphatase-1. Author(s): Gasa R, Clark C, Yang R, DePaoli-Roach AA, Newgard CB. Source: The Journal of Biological Chemistry. 2002 January 11; 277(2): 1524-30. Epub 2001 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707447

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Risk factors for death in men with glucose intolerance. Author(s): Jarrett RJ. Source: Bmj (Clinical Research Ed.). 1993 August 28; 307(6903): 569. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8401007

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Risk factors for glucose intolerance in active acromegaly. Author(s): Kreze A, Kreze-Spirova E, Mikulecky M. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2001 November; 34(11): 1429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668352

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Role of glucose intolerance in cardiac diastolic function in essential hypertension. Author(s): Nagano N, Nagano M, Yo Y, Iiyama K, Higaki J, Mikami H, Ogihara T. Source: Hypertension. 1994 June; 23(6 Pt 2): 1002-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8206582

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Role of hyperinsulinemia and glucose intolerance in the pathogenesis of nonalcoholic fatty liver in patients with normal body weight. Author(s): Lee JH, Rhee PL, Lee JK, Lee KT, Kim JJ, Koh KC, Paik SW, Rhee JC, Choi KW. Source: Korean J Intern Med. 1998 February; 13(1): 12-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9538625

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Role of insulin in the pathogenesis of hypertension associated with glucose intolerance. Author(s): Takahashi H, Nakanishi T, Nishimura M, Fukumitsu S, Yoshimura M. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1993 May; 15(3): 575-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8490597

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Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis. Author(s): Austin A, Kalhan SC, Orenstein D, Nixon P, Arslanian S. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 July; 79(1): 80-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027259

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Screening for glucose intolerance in siblings of children with diabetes. Author(s): Rosenbloom AL, Bianchi R, Chin FT. Source: Metabolism: Clinical and Experimental. 1973 February; 22(2): 351-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4687960

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Screening for insulin receptor gene DNA polymorphisms associated with glucose intolerance in a Scandinavian population. Author(s): Sten-Linder M, Vilhelmsdotter S, Wedell A, Stern I, Pollare T, Arner P, Efendic S, Luft R, Luthman H. Source: Diabetologia. 1991 April; 34(4): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1676686

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Secondary hyperparathyroidism and glucose intolerance in children with uremia. Author(s): Mak RH, Turner C, Haycock GB, Chantler C. Source: Kidney International. Supplement. 1983 December; 16: S128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6588242

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Secondary syphilis presenting with arthritis, hepatitis, and glucose intolerance. Author(s): Williams WC, Marion GS. Source: The Journal of Family Practice. 1987 November; 25(5): 509-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3681210

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Senile cataract and glucose intolerance: the Israel Study of glucose Intolerance Obesity and Hypertension (The Israel GOH Study). Author(s): Karasik A, Modan M, Halkin H, Treister G, Fuchs Z, Lusky A. Source: Diabetes Care. 1984 January-February; 7(1): 52-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6705665

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Sepsis, glucose intolerance, and protein malnutrition: a metabolic paradox. Author(s): Dahn M, Kirkpatrick JR, Bouwman D. Source: Archives of Surgery (Chicago, Ill. : 1960). 1980 December; 115(12): 1415-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6778457

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Serum reverse T3 assay for predicting glucose intolerance in uremic patients on dialysis therapy. Author(s): De Marchi S, Cecchin E, Villalta D, Tesio F. Source: Clinical Nephrology. 1987 April; 27(4): 189-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3581526

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Should all pregnant women be screened for gestational glucose intolerance? Author(s): Ales KL, Santini DL. Source: Lancet. 1989 May 27; 1(8648): 1187-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2566747

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Should we treat minor degrees of glucose intolerance in pregnancy? Author(s): Bonomo M, Gandini ML, Farina A, Bonfadini E, Pisoni MP, Prudenziati A, Mion E, Greco P. Source: Ann Ist Super Sanita. 1997; 33(3): 393-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9542269

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Size at birth and glucose intolerance in a relatively genetically homogeneous, highbirth weight population. Author(s): Birgisdottir BE, Gunnarsdottir I, Thorsdottir I, Gudnason V, Benediktsson R. Source: The American Journal of Clinical Nutrition. 2002 August; 76(2): 399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145013

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Sleep-disordered breathing, glucose intolerance, and insulin resistance. Author(s): Punjabi NM, Ahmed MM, Polotsky VY, Beamer BA, O'Donnell CP. Source: Respiratory Physiology & Neurobiology. 2003 July 16; 136(2-3): 167-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853008

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Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Author(s): Fowkes FG, Housley E, Riemersma RA, Macintyre CC, Cawood EH, Prescott RJ, Ruckley CV. Source: American Journal of Epidemiology. 1992 February 15; 135(4): 331-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1550087

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Somatostatin and diabetes mellitus: the role of glucagon in diabetic hyperglycemia and glucose intolerance. Author(s): Wahren J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1976 October; 36(6): 497-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1006141

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Standardized comparison of glucose intolerance in west African-origin populations of rural and urban Cameroon, Jamaica, and Caribbean migrants to Britain. Author(s): Mbanya JC, Cruickshank JK, Forrester T, Balkau B, Ngogang JY, Riste L, Forhan A, Anderson NM, Bennett F, Wilks R. Source: Diabetes Care. 1999 March; 22(3): 434-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10097925

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Studies of glucose intolerance in cirrhosis of the liver. Author(s): Shankar TP, Solomon SS, Duckworth WC, Himmelstein S, Gray S, Jerkins T, Bobal MA, Iyer RS. Source: The Journal of Laboratory and Clinical Medicine. 1983 October; 102(4): 459-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6352838

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Studies of glucose intolerance in septic injured patients. Author(s): Gump FE, Long C, Killian P, Kinney JM. Source: The Journal of Trauma. 1974 May; 14(5): 378-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4823949

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Studies on glucose intolerance in chronic renal failure: estimation of insulin sensitivity before and after initiation of hemodialysis. Author(s): Oshida Y, Sato Y, Shiraishi S, Sakamoto N. Source: Clinical Nephrology. 1987 July; 28(1): 35-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3304745

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Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance. Author(s): Fernandez-Real JM, Pugeat M, Emptoz-Bonneton A, Ricart W. Source: Metabolism: Clinical and Experimental. 2001 October; 50(10): 1248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11586502

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Subclinical states of glucose intolerance and risk of death in the U.S. Author(s): Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Source: Diabetes Care. 2001 March; 24(3): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11289466

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Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Author(s): Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB. Source: Nature Medicine. 2000 August; 6(8): 924-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10932232

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Teenage pregnancy. BMI and patterns in weight gain and their effect on glucose intolerance. Author(s): Kurzel RB. Source: Annals of the New York Academy of Sciences. 1997 May 28; 817: 365-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9239208

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The association of physical activity with obesity, fat distribution and glucose intolerance in Pima Indians. Author(s): Kriska AM, LaPorte RE, Pettitt DJ, Charles MA, Nelson RG, Kuller LH, Bennett PH, Knowler WC. Source: Diabetologia. 1993 September; 36(9): 863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8405759

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The genetics of the glucose intolerance disorders. Author(s): Rotter JI, Rimoin DL. Source: The American Journal of Medicine. 1981 January; 70(1): 116-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7457485

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The glucose intolerance of acute pancreatitis: hormonal response to arginine. Author(s): Solomon SS, Duckworth WC, Jallepalli P, Bobal MA, Iyer R. Source: Diabetes. 1980 January; 29(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6991312

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The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation. Author(s): Hjelmesaeth J, Hagen M, Hartmann A, Midtvedt K, Egeland T, Jenssen T. Source: Clinical Transplantation. 2002 December; 16(6): 389-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437616

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The negative association between traditional physical activities and the prevalence of glucose intolerance in Alaska Natives. Author(s): Adler AI, Boyko EJ, Schraer CD, Murphy NJ. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1996 June; 13(6): 555-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8799660

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The postprandial state: mechanisms of glucose intolerance. Author(s): Dinneen SF. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1997 August; 14 Suppl 3: S19-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272609

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The prevalence of three major risk factors of cardiovascular disease: (glucose intolerance, hypertension, hyperlipoproteinaemia) in a sample of Thai social class 1. Author(s): Viseshakul D, Premwatana P, Chulrojanamontri V, Kewsiri D. Source: J Med Assoc Thai. 1979 March; 62(3): 116-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=429940

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The relationship between insulin resistance and insulin secretion in Japanese subjects with borderline glucose intolerance. Author(s): Wasada T, Arii H, Kuroki H, Saeki A, Katsumori K, Saito S, Omori Y. Source: Diabetes Research and Clinical Practice. 1995 October; 30(1): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8745206

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The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects. Author(s): Niemi M, Kervinen K, Rantala A, Kauma H, Paivansalo M, Savolainen MJ, Lilja M, Kesaniemi YA. Source: Gut. 1999 April; 44(4): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075965

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The role of growth hormone in the glucose intolerance of uremia. Author(s): DeFronzo RA, Tobin J, Boden G, Andres R. Source: Acta Diabetol Lat. 1979 October-December; 16(4): 279-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=399149

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The role of obesity in the association of cardiovascular risk factors and glucose intolerance in small Japanese and North American communities. Author(s): Adachi H, Goetz FC, Jacobs DR, Tsuruta M, Hirai Y, Fujiura Y, Imaizumi T. Source: Diabetes Research and Clinical Practice. 2000 July; 49(1): 41-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10808062

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The severity of periodontal disease is associated with the development of glucose intolerance in non-diabetics: the Hisayama study. Author(s): Saito T, Shimazaki Y, Kiyohara Y, Kato I, Kubo M, Iida M, Koga T. Source: Journal of Dental Research. 2004 June; 83(6): 485-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15153457

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Thyroid hormone excess and glucose intolerance. Author(s): Dimitriadis GD, Raptis SA. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109 Suppl 2: S22539. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11460573

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Tissue glycogen content and glucose intolerance. Author(s): Kasuga M, Ogawa W, Ohara T. Source: The Journal of Clinical Investigation. 2003 May; 111(9): 1282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727918

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Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance. Author(s): Miller NR, Moses H. Source: Jama : the Journal of the American Medical Association. 1978 October 20; 240(17): 1887-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=691201

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Treatment of glucose intolerance in pregnancy: staged diabetes management. Author(s): Mazze RS. Source: Int J Clin Pharmacol Ther Toxicol. 1993 October; 31(10): 497-505. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8262688

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Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Author(s): Milla CE, Warwick WJ, Moran A. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 1): 891-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988101

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Trp64Arg mutation of beta 3-adrenergic receptor and insulin sensitivity in subjects with glucose intolerance. Author(s): Arii K, Suehiro T, Yamamoto M, Ito H, Ikeda Y, Nakauchi Y, Hashimoto K. Source: Intern Med. 1997 September; 36(9): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9313101

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Ultrasonographic manifestations of carotid atherosclerosis and glucose intolerance in elderly eastern Finnish men. Author(s): Tuomilehto J, Qiao Q, Salonen R, Nissinen A, Salonen JT. Source: Diabetes Care. 1998 August; 21(8): 1349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702446

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Undiagnosed glucose intolerance encountered in clinical practice: reappraisal of the use of the oral glucose tolerance test. Author(s): Hwu CM, Kwok CF, Ku BI, Lin YT, Lee YS, Hsiao LC, Lee SH, Ho LT. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2001 August; 64(8): 435-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720141

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Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes Project. Author(s): Williams DR, Wareham NJ, Brown DC, Byrne CD, Clark PM, Cox BD, Cox LJ, Day NE, Hales CN, Palmer CR, et al. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1995 January; 12(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7712700

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Use of antihypertensive agents in patients with glucose intolerance. Author(s): McKenney JM, Goodman RP, Wright JT Jr. Source: Clin Pharm. 1985 November-December; 4(6): 649-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2866862

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Validation of capillary glucose measurements to detect glucose intolerance or type 2 diabetes mellitus in the general population. Author(s): Kruijshoop M, Feskens EJ, Blaak EE, de Bruin TW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004 March; 341(1-2): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14967156

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Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy. Author(s): Jovanovic-Peterson L, Peterson CM. Source: Journal of the American College of Nutrition. 1996 February; 15(1): 14-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8632110

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Waist to hip ratio, body mass index, and glucose intolerance from Funagata population-based diabetes survey in Japan. Author(s): Sekikawa A, Eguchi H, Igarashi K, Tominaga M, Abe T, Fukuyama H, Kato T. Source: The Tohoku Journal of Experimental Medicine. 1999 September; 189(1): 11-20. Erratum In: Tohoku J Exp Med 2000 April; 190(4): 295. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622204

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Weight change amongst Nauruans over 6.5 years: extent, and association with glucose intolerance. Author(s): Sicree RA, Zimmet PZ, King H, Coventry JS. Source: Diabetes Research and Clinical Practice. 1987 November-December; 3(6): 327-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3665732

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Weight history, glucose intolerance, and insulin levels in middle-aged Swedish men. Author(s): Carlsson S, Persson PG, Alvarsson M, Efendic S, Norman A, Svanstrom L, Ostenson CG, Grill V. Source: American Journal of Epidemiology. 1998 September 15; 148(6): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753008

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Which cutoff level should be used in screening for glucose intolerance in pregnancy? Definition of Screening Methods for Gestational Diabetes Study Group of the Lombardy Section of the Italian Society of Diabetology. Author(s): Bonomo M, Gandini ML, Mastropasqua A, Begher C, Valentini U, Faden D, Morabito A. Source: American Journal of Obstetrics and Gynecology. 1998 July; 179(1): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704785

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CHAPTER 2. NUTRITION AND GLUCOSE INTOLERANCE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and glucose intolerance.

Finding Nutrition Studies on Glucose Intolerance The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “glucose intolerance” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on glucose intolerance: •

Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population. Author(s): National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Source: Harris, M I Diabetes-Care. 1991 May; 14(5): 366-74 0149-5992

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Inverse association between fish intake and risk of glucose intolerance in normoglycemic elderly men and women. Author(s): Department of Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands. Source: Feskens, E J Bowles, C H Kromhout, D Diabetes-Care. 1991 November; 14(11): 935-41 0149-5992

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Prevalence and determinants of glucose intolerance in a Dutch caucasian population. The Hoorn Study. Author(s): Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, the Netherlands. [email protected] Source: Mooy, J M Grootenhuis, P A de Vries, H Valkenburg, H A Bouter, L M Kostense, P J Heine, R J Diabetes-Care. 1995 September; 18(9): 1270-3 0149-5992

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Prevalence of glucose intolerance among Native Hawaiians in two rural communities. Native Hawaiian Health Research (NHHR) Project. Author(s): Pacific Biomedical Research Center, Manoa, Hawaii. [email protected] Source: Grandinetti, A Chang, H K Mau, M K Curb, J D Kinney, E K Sagum, R Arakaki, R F Diabetes-Care. 1998 April; 21(4): 549-54 0149-5992

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Subclinical states of glucose intolerance and risk of death in the U.S. Author(s): Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland, USA. Source: Saydah, S H Loria, C M Eberhardt, M S Brancati, F L Diabetes-Care. 2001 March; 24(3): 447-53 0149-5992

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Ultrasonographic manifestations of carotid atherosclerosis and glucose intolerance in elderly eastern Finnish men. Author(s): Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland. [email protected] Source: Tuomilehto, J Qiao, Q Salonen, R Nissinen, A Salonen, J T Diabetes-Care. 1998 August; 21(8): 1349-52 0149-5992

The following information is typical of that found when using the “Full IBIDS Database” to search for “glucose intolerance” (or a synonym): •

Amitraz-induced glucose intolerance in rats: antagonism by yohimbine but not by prazosin. Author(s): Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011. Source: Smith, B E Hsu, W H Yang, P C Arch-Toxicol. 1990; 64(8): 680-3 0340-5761

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Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Author(s): Cellular Mechanisms Research Group, London Hospital Medical College, UK.

Nutrition

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Source: Boucher, B J Ewen, S W Stowers, J M Diabetologia. 1994 January; 37(1): 49-55 0012-186X •

Glucose tolerance and insulin response to glucose load before and after enzyme inducing therapy in subjects with glucose intolerance and patients with NIDDM having hyperinsulinemia or relative insulin deficiency. Author(s): Department of Internal Medicine, University of Oulu, Finland. Source: Sotaniemi, E A Karvonen, I Diabetes-Res. 1989 July; 11(3): 131-9 0265-5985

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Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index. Author(s): Department of Family Medicine, Umea University, Sweden. Source: Rolandsson, O Hagg, E Hampe, C Sullivan, E P Nilsson, M Jansson, G Hallmans, G Lernmark, A Diabetologia. 1999 May; 42(5): 555-9 0012-186X

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Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice. Author(s): Medical Clinic III, Justus Liebig University, Giessen, Germany. Source: Linn, T Loewk, E Schneider, K Federlin, K Diabetologia. 1993 December; 36(12): 1245-51 0012-186X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to glucose intolerance; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Minerals Chromium Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND GLUCOSE INTOLERANCE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to glucose intolerance. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to glucose intolerance and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “glucose intolerance” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to glucose intolerance: •

A combined high-fiber, low-glycemic index diet normalizes glucose tolerance and reduces hyperglycemia and hyperinsulinemia in adults with hepatic cirrhosis. Author(s): Barkoukis H, Fiedler KM, Lerner E. Source: Journal of the American Dietetic Association. 2002 October; 102(10): 1503-7; Discussion 1507-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12396175

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A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes. Author(s): Wilkes JJ, Bonen A, Bell RC. Source: The American Journal of Physiology. 1998 October; 275(4 Pt 1): E679-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755088

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A study on Asian Indian and American vegetarians: indications of a racial predisposition to glucose intolerance. Author(s): Scholfield DJ, Behall KM, Bhathena SJ, Kelsay J, Reiser S, Revett KR. Source: The American Journal of Clinical Nutrition. 1987 December; 46(6): 955-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3318380

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Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy. Author(s): Koohestani N, Chia MC, Pham NA, Tran TT, Minkin S, Wolever TM, Bruce WR. Source: Carcinogenesis. 1998 September; 19(9): 1679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9771941

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Acute effect of low-calorie and low-carbohydrate diet on serum triiodothyronineresponse to glucose ingestion and its relation to glucose tolerance. Author(s): Koh H, Tsushima M, Waki M, Matsuyama T. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1994 October; 26(10): 470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7851870

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Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas. Author(s): Bhattacharya SK, Bhattacharya A, Chakrabarti A. Source: Indian J Exp Biol. 2000 February; 38(2): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11218827

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Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Author(s): Bhattacharya SK, Muruganandam AV. Source: Pharmacology, Biochemistry, and Behavior. 2003 June; 75(3): 547-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895672

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Age-associated changes in the endocrine system. Author(s): Winger JM, Hornick T. Source: Nurs Clin North Am. 1996 December; 31(4): 827-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8969342

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Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Author(s): Sheela CG, Kumud K, Augusti KT. Source: Planta Medica. 1995 August; 61(4): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480182

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Antihypertensive therapy in diabetic patients. Author(s): Weidmann P, Boehlen LM, de Courten M, Ferrari P.

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Source: Journal of Human Hypertension. 1992 December; 6 Suppl 2: S23-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1289510 •

Balanced intakes of natural triglycerides for optimum nutrition: an evolutionary and phytochemical perspective. Author(s): Broadhurst CL. Source: Medical Hypotheses. 1997 September; 49(3): 247-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9293470

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Beneficial effects of fish oil on glucose metabolism in spontaneously hypertensive rats. Author(s): Ajiro K, Sawamura M, Ikeda K, Nara Y, Nishimura M, Ishida H, Seino Y, Yamori Y. Source: Clinical and Experimental Pharmacology & Physiology. 2000 May-June; 27(5-6): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10831245

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Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Author(s): Boucher BJ, Ewen SW, Stowers JM. Source: Diabetologia. 1994 January; 37(1): 49-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8150230

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Carbohydrate intake and body mass index in relation to the risk of glucose intolerance in an elderly population. Author(s): Feskens EJ, Bowles CH, Kromhout D. Source: The American Journal of Clinical Nutrition. 1991 July; 54(1): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2058574

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Chromium as a supplement. Author(s): Lukaski HC. Source: Annual Review of Nutrition. 1999; 19: 279-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448525

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Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Author(s): Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A. Source: The American Journal of Clinical Nutrition. 1977 April; 30(4): 531-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=192066

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Chromium, glucose intolerance and diabetes. Author(s): Anderson RA.

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Source: Journal of the American College of Nutrition. 1998 December; 17(6): 548-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853533 •

Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Author(s): Misra A, Garg A. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2003 March; 82(2): 129-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640189

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Cystic fibrosis-related diabetes. Author(s): Mackie AD, Thornton SJ, Edenborough FP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 June; 20(6): 425-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786675

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Decreased carbohydrate intake is more important than increased fat intake in the glucose intolerance by a low-carbohydrate/high-fat diet. Author(s): Wang Y, Kaneko T, Wang PY, Sato A. Source: Diabetes Research and Clinical Practice. 2002 January; 55(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755480

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Diabetes is related to fatty acid imbalance in Eskimos. Author(s): Ebbesson SO, Kennish J, Ebbesson L, Go O, Yeh J. Source: Int J Circumpolar Health. 1999 April; 58(2): 108-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10429340

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Diabetes mellitus or an impaired glucose tolerance as a potential complicating factor in patients treated with high-dose therapy and autologous bone marrow transplantation. Author(s): Schouten HC, Maragos D, Vose J, Armitage JO. Source: Bone Marrow Transplantation. 1990 November; 6(5): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2291995

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Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production. Author(s): Holness MJ, Greenwood GK, Smith ND, Sugden MC. Source: Endocrinology. 2003 September; 144(9): 3958-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933670

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Diet selection and metabolic fuels in three models of diabetes mellitus. Author(s): Bartness TJ, Rowland NE.

Alternative Medicine 101

Source: Physiology & Behavior. 1983 October; 31(4): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6361816 •

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats. Author(s): Appleton DJ, Rand JS, Sunvold GD, Priest J. Source: Journal of Feline Medicine and Surgery. 2002 March; 4(1): 13-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11869052

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Dietary factors in the aetiology of diabetes. Author(s): Virtanen SM, Aro A. Source: Annals of Medicine. 1994 December; 26(6): 469-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7695875

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Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged insulin levels in rats fed a high sucrose diet. Author(s): Lombardo YB, Chicco A, D'Alessandro ME, Martinelli M, Soria A, Gutman R. Source: Biochimica Et Biophysica Acta. 1996 January 19; 1299(2): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555262

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Dietary fructose in the management of intractable diarrhea of infancy. Author(s): Clark JH, Bullock L, Fitzgerald JF. Source: Journal of Pediatric Gastroenterology and Nutrition. 1986 January; 5(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3080579

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Differential effects of honey, sucrose, and fructose on blood sugar levels. Author(s): Shambaugh P, Worthington V, Herbert JH. Source: Journal of Manipulative and Physiological Therapeutics. 1990 July-August; 13(6): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2394949

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Distinct role of adiposity and insulin resistance in glucose intolerance: studies in ventromedial hypothalamic-lesioned obese rats. Author(s): Kageyama A, Hirano T, Kageyama H, Osaka T, Namba Y, Tsuji M, Adachi M, Inoue S. Source: Metabolism: Clinical and Experimental. 2002 June; 51(6): 716-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037724

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Does a high-carbohydrate diet have different effects in NIDDM patients treated with diet alone or hypoglycemic drugs? Author(s): Parillo M, Giacco R, Ciardullo AV, Rivellese AA, Riccardi G.

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Source: Diabetes Care. 1996 May; 19(5): 498-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732716 •

Does dietary fat influence insulin action? Author(s): Storlien LH, Kriketos AD, Jenkins AB, Baur LA, Pan DA, Tapsell LC, Calvert GD. Source: Annals of the New York Academy of Sciences. 1997 September 20; 827: 287-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9329762

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Effect of dietary fish oil on 2-deoxy-D-3H glucose uptake in isolated adipocytes of rats fed various diets. Author(s): Macho L, Fickova M, Sebokova E, Mitkova A, Klimes I. Source: Annals of the New York Academy of Sciences. 1993 June 14; 683: 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8352445

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Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia. Author(s): Minami A, Ishimura N, Sakamoto S, Takishita E, Mawatari K, Okada K, Nakaya Y. Source: The British Journal of Nutrition. 2002 February; 87(2): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895168

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Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor alpha (ERalpha): a potential role for estrogen receptor beta (ERbeta). Author(s): Naaz A, Zakroczymski M, Heine P, Taylor J, Saunders P, Lubahn D, Cooke PS. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 November-December; 34(11-12): 758-63. Erratum In: Horm Metab Res. 2003 April; 35(4): 271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660895

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Effect of pinitol treatment on insulin action in subjects with insulin resistance. Author(s): Davis A, Christiansen M, Horowitz JF, Klein S, Hellerstein MK, Ostlund RE Jr. Source: Diabetes Care. 2000 July; 23(7): 1000-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895854

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Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats. Author(s): Muruganandam AV, Kumar V, Bhattacharya SK.

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Source: Indian J Exp Biol. 2002 October; 40(10): 1151-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693696 •

Effects of chromium picolinate supplementation on insulin sensitivity, serum lipids, and body weight in dexamethasone-treated rats. Author(s): Kim DS, Kim TW, Park IK, Kang JS, Om AS. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 589-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979390

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Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity. Author(s): Wang Y, Aggarwal SK. Source: Anti-Cancer Drugs. 1997 October; 8(9): 853-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9402312

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One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Author(s): Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto E. Source: Atherosclerosis. 1998 April; 137(2): 419-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9622285

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Plasma catecholamines, dietary carbohydrate, and glucose intolerance: a comparison between young and old men. Author(s): Chen M, Halter JB, Porte D Jr. Source: The Journal of Clinical Endocrinology and Metabolism. 1986 June; 62(6): 1193-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3700584

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Role of 5-hydroxytryptamine (serotonin) in oral glucose intolerance. Author(s): Narvanen S. Source: Scand J Clin Lab Invest Suppl. 1983; 167: 1-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6581528

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Short-term treatment of glucose intolerance in middle-aged subjects by diet, exercise and sulfonylurea. Author(s): Cederholm J. Source: Upsala Journal of Medical Sciences. 1985; 90(3): 229-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4095819

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to glucose intolerance; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Obesity Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the

Alternative Medicine 105

MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON GLUCOSE INTOLERANCE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “glucose intolerance” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glucose intolerance, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Glucose Intolerance By performing a patent search focusing on glucose intolerance, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Glucose Intolerance

The following is an example of the type of information that you can expect to obtain from a patent search on glucose intolerance: •

Liquid nutritional formula for glucose intolerance Inventor(s): Besozzi; Elizabeth M. (Columbus, OH), Cashmere; Karen A. (Columbus, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 4,921,877 Date filed: December 16, 1987 Abstract: An improved nutritionally complete formula containing a unique fibercontaining carbohydrate blend, at a relatively low concentration; a unique fat blend, at a relatively high concentration; protein; carnitine; myoinositol; vitamins and minerals, including chromium. This formula is for the dietary management of patients with glucose intolerance. Excerpt(s): The invention relates to improved enteral nutritional formulas and more particularly to formulas which provide protein, low carbohydrate, high fat, dietary fiber and micronutrients specific to the needs of glucose intolerant individuals. Primary treatment for glucose intolerance is strict adherence to a diet which minimizes postprandial glucose response, and in many cases, use of medications (insulin or oral hypoglycemic agents). The American Diabetes Association (ADA) currently recommends a diet in which protein accounts for 12-20% total calories (kcal), carbohydrate for 50-60% kcal, and fat for the remaining kcal (about 30%). Diabetes Care 2:250-253, 1979. The ADA also recommends consumption of complex carbohydrates that are high in dietary fiber (40 g/day for men, 25 g/day for women), and consumption of fats that are low in cholesterol (