Diabetes in America

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Preface

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iabetes in America, 2nd Edition, has been sponsored by the National Diabetes Data Group (NDDG) of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The NDDG was established in 1977 in response to recommendations of the U.S. National Commission on Diabetes. Its purposes are to define needs for information that can address the important scientific and public health issues in diabetes, facilitate research on the epidemiologic and clinical aspects of diabetes, and to develop reliable and accurate information on the scope and impact of diabetes in the U.S. population.

dence, sociodemographic and metabolic characteristics, risk factors for developing diabetes, and mortality; the myriad of complications that affect patients with diabetes; characteristics of therapy and medical care for diabetes; economic aspects, including health insurance and health care costs; and diabetes in special populations, including blacks, Hispanics, Asian and Pacific Islanders, Native Americans, and pregnant women. Diabetes in America, 2nd Edition has been designed to serve as a reliable scientific resource for assessing the scope and impact of diabetes and its complications, determining health policy and priorities in diabetes, and identifying areas of need in research. The intended audience includes health policy makers at the local and federal levels who need a sound quantitative base of knowledge to use in decision making; clinicians who need to know the probability that their patients will develop diabetes and the prognosis of the disease for complications and premature mortality; persons with diabetes and their families who need sound information on which to make decisions about their life with diabetes; and the research community which needs to identify areas where important scientific knowledge is lacking. I hope you will find that these purposes have been fulfilled.

The authors of Diabetes in America, 2nd Edition, are recognized experts in their fields. Their participation brings to the document not only their specific scientific expertise, but also the spectrum of disciplines that reflect the broad interests and issues in the diabetes community. The book represents, in the judgment of its authors and editors, a compilation and assessment of the most valid, accurate, and useful data on diabetes and its complications in the United States. It complements the first edition of Diabetes in America, published by the NDDG in 1985, which remains a valid reference work for the field of diabetes. Five general areas are addressed in the 36 chapters. These include the descriptive epidemiology of diabetes in the United States based on national surveys and community-based studies, including prevalence, inci-

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Maureen I. Harris, PhD, MPH Director, National Diabetes Data Group

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National Diabetes Data Group

Maureen I. Harris, PhD, MPH, Director, National Diabetes Data Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Peter H. Bennett, MB, FRCP, FFCM, Chief, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ Edward J. Boyko, MD, MPH, Associate Professor, Department of Medicine, University of Washington, and Staff Physician, Veterans Affairs Medical Center, Seattle, WA Catherine C. Cowie, PhD, MPH, Senior Epidemiologist, Social and Scientific Systems, Inc., Bethesda, MD Janice S. Dorman, PhD, Associate Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA James E. Everhart, MD, MPH, Chief, Epidemiology and Clinical Trials Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD William H. Herman, MD, MPH, Medical Epidemiologist, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control, Atlanta, GA Donald B. Martin, MD, Professor of Medicine, Rodebaugh Diabetes Center, University of Pennsylvania Medical Center, Philadelphia, PA P.J. Palumbo, MD, Endocrinologist and Diabetologist, Mayo Clinic, Scottsdale, AZ Gayle E. Reiber, MPH, PhD, Assistant Professor, Departments of Health Services and Epidemiology, University of Washington, and Research Health Science Specialist, Veterans Affairs Medical Center, Seattle, WA Michael P. Stern, MD, Professor, Department of Medicine, University of Texas Health Science Center, San Antonio, TX

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Editorial Board and Authors for Diabetes in America, 2nd Edition EDITORIAL BOARD

Maureen I. Harris, PhD, MPH, Director, National Diabetes Data Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Catherine C. Cowie, PhD, MPH, Senior Epidemiologist, Social and Scientific Systems, Inc., Bethesda, MD Michael P. Stern, MD, Professor, Department of Medicine, University of Texas Health Science Center, San Antonio, TX Edward J. Boyko, MD, MPH, Associate Professor, Department of Medicine, University of Washington, and Staff Physician, Veterans Affairs Medical Center, Seattle, WA Gayle E. Reiber, MPH, PhD, Assistant Professor, Departments of Health Services and Epidemiology, University of Washington, and Research Health Science Specialist, Veterans Affairs Medical Center, Seattle, WA Peter H. Bennett, MB, FRCP, FFCM, Chief, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ

AUTHORS

Ronald E. Aubert, PhD, Epidemiologist, Prudential Center for Health Care Research, Atlanta, GA David J. Ballard, MD, PhD, Director, Center for Clinical Evaluation Sciences, Emory University, Atlanta, GA Elizabeth Barrett-Connor, MD, Professor and Chair, Department of Family and Preventive Medicine, School of Medicine, University of California at San Diego, La Jolla, CA Peter H. Bennett, MB, FRCP, FFCM, Chief, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ Edward J. Boyko, MD, MPH, Associate Professor, Department of Medicine, University of Washington, and Staff Physician, Veterans Affairs Medical Center, Seattle, WA Thomas A. Buchanan, MD, Associate Professor of Medicine and Obstetrics and Gynecology, University of Southern California School of Medicine, and Staff Physician, Los Angeles County and University of Southern California Medical Center, Los Angeles, CA Yue-Fang Chang, PhD, Research Fellow, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA

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Yen-Pin Chiang, PhD, Research Assistant Professor, Georgetown University Medical Center, Washington, DC (currently on the staff of the Health Care Financing Administration, U.S. Department of Health and Human Services, Washington, DC) Beth Cocanougher, MPH, Cardiac Research Nurse, The Methodist Hospital, Houston, TX Donald R. Coustan, MD, Professor and Chairman, Department of Obstetrics and Gynecology, Brown University School of Medicine, and Obstetrician and Gynecologist in Chief, Women and Infants’ Hospital of Rhode Island, Providence, RI Catherine C. Cowie, PhD, MPH, Senior Epidemiologist, Social and Scientific Systems, Inc., Bethesda, MD Partha Deb, PhD, Assistant Professor, Department of Economics, Indiana University-Purdue University, Indianapolis, IN Janice S. Dorman, PhD, Associate Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Richard C. Eastman, MD, Director, Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Mark S. Eberhardt, PhD, Commissioned Officer, Office of Analysis, Epidemiology, and Health Promotion, National Center for Health Statistics, Hyattsville, MD James E. Everhart, MD, MPH, Chief, Epidemiology and Clinical Trials Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Brian J. Fertig, MD, Fellow in Endocrinology, Division of Endocrinology and Diabetes, Department of Medicine, Tulane University Medical Center, New Orleans, LA Howard Fishbein, DrPH, Senior Epidemiologist, The Gallup Organization, Rockville, MD Wilfred Y. Fujimoto, MD, Professor, Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA Om P. Ganda, MD, Diabetologist, Joslin Diabetes Center, Boston, MA Jeffrey A. Gavard, PhD, Fellow in Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO Linda S. Geiss, MA, Statistician, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control, Atlanta, GA Robert J. Genco, DDS, PhD, Distinguished Professor and Chair, Department of Oral Biology, School of Dentistry, State University of New York, Buffalo, NY Dorothy Gohdes, MD, Director, Indian Health Service Diabetes Program, Albuquerque, NM Richard F. Hamman, MD, DrPH, Professor, Department of Preventive Medicine and Biometrics, University of Colorado Health Science Center, Denver, CO Maureen I. Harris, PhD, MPH, Director, National Diabetes Data Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD William H. Herman, MD, MPH, Medical Epidemiologist, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control, Atlanta, GA xii

Gail R. Janes, PhD, MS, Epidemiologist, Office of Surveillance and Analysis, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA Jonathan C. Javitt, MD, MPH, Associate Professor of Ophthalmology and Public Policy, and Director, Worthen Center for Eye Care Research, Georgetown University Medical Center, Washington, DC Susan J. Kenny, PhD, Senior Biostatistician, Quintiles Inc., Research Triangle Park, NC Barbara E.K. Klein, MD, MPH, Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI Ronald Klein, MD, MPH, Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI William C. Knowler, MD, DrPH, Chief, Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ Anita N. Koehler, MPH, RD, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Department of Nutrition, Children’s Hospital of Pittsburgh, Pittsburgh, PA Lewis H. Kuller, MD, DrPH, Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Ronald E. LaPorte, PhD, Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA Benjamin A. Lipsky, MD, Associate Professor, Department of Medicine, University of Washington, and Staff Physician, Veterans Affairs Medical Center, Seattle, WA Harald Löe, DDS, University Professor, Department of Periodontology, University of Connecticut Dental School, Farmington, CT Patrick J. Lustman, PhD, Associate Professor of Medical Psychology in Psychiatry, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO Donald B. Martin, MD, Professor of Medicine, Rodebaugh Diabetes Center, University of Pennsylvania Medical Center, Philadelphia, PA Masato Matsushima, MD, Research Fellow, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Jennifer A. Mayfield, MD, MPH, Associate Professor, Department of Family Medicine, Indiana University-Purdue University, Indianapolis, IN Bridget J. McCarthy, MS, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA L. Joseph Melton III, MD, Clinical Epidemiologist, Department of Health Sciences Research, Mayo Clinic, Rochester, MN Braxton D. Mitchell, PhD, Staff Scientist, Southwest Foundation for Biomedical Research, San Antonio, TX Robert G. Nelson, MD, MPH, Special Expert, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ

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Leslie A. O’Leary, PhD, Research Associate, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Trevor Orchard, MD, Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA P.J. Palumbo, MD, Endocrinologist and Diabetologist, Mayo Clinic, Scottsdale, AZ David J. Pettitt, MD, Assistant Chief, Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ Enrico Portuese, MPH, Research Assistant, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA D.E.B. Potter, MS, Senior Survey Statistician, Agency for Health Care Policy and Research, Department of Health and Human Services, Rockville, MD Gayle E. Reiber, MPH, PhD, Assistant Professor, Departments of Health Services and Epidemiology, University of Washington, and Research Health Science Specialist, Veterans Affairs Medical Center, Seattle, WA Marian Rewers, MD, PhD, Associate Professor, Department of Preventive Medicine and Biometrics, University of Colorado Health Science Center, Denver, CO Jeffrey M. Roseman, MD, PhD, MPH, Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, Birmingham, AL David A. Simmons, MD, Associate Professor of Medicine, Rodebaugh Diabetes Center, University of Pennsylvania Medical Center, Philadelphia, PA Douglas G. Smith, MD, Assistant Professor, Department of Orthopaedic Surgery, University of Washington, and Staff Physician, Seattle Veterans Affairs Medical Center, Seattle, WA Philip J. Smith, PhD, Division of Tuberculosis, National Center for Prevention Services, Centers for Disease Control, Atlanta, GA Thomas J. Songer, PhD, Assistant Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Michael P. Stern, MD, Professor, Department of Medicine, University of Texas Health Science Center, San Antonio, TX Eugene S. Tull, DrPH, Assistant Professor, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA Deborah L. Wingard, PhD, Associate Professor, Department of Family and Preventive Medicine, School of Medicine, University of California at San Diego, La Jolla, CA

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Chapter 1

Summary Maureen I. Harris, PhD, MPH

occurs in ~3%-5% of all pregnancies. Impaired glucose tolerance (IGT) is a class that encompasses people whose OGTT values are intermediate between normal and diabetic; ~11% of adults had IGT when tested by oral glucose challenge in the 1976-80 Second National Health and Nutrition Examination Survey (NHANES II).

DESCRIPTIVE EPIDEMIOLOGY

CLASSIFICATION AND DIAGNOSTIC CRITERIA Diabetes mellitus comprises a heterogeneous group of disorders characterized by high blood glucose levels. Four major types of diabetes have been defined: insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), gestational diabetes mellitus (GDM), and diabetes secondary to other conditions. IDDM characteristically presents with prominent diabetes symptoms and extreme hyperglycemia. NIDDM can be diagnosed by the presence of the classical signs and symptoms of diabetes together with unequivocally elevated blood glucose levels; by fasting plasma glucose (FPG) ≥140 mg/dl; or by venous plasma glucose ≥200 mg/dl at 2 hours after a 75-g oral glucose challenge. Criteria for GDM vary but require an oral glucose challenge and measurement of post-load plasma glucose.

Insulin-Dependent Diabetes The prevalence of IDDM with onset at age 30 years and obesity >120% of ideal body weight as additional risk factors and a screening test threshold of 140 mg/dl, found a sensitivity of 62% (46/74), but specificity could not be calculated from the data presented21. It is thus apparent that using historic risk factors to screen for gestational diabetes is relatively inefficient, since a large proportion of the population has risk factors present and a significant number of those with gestational diabetes do not have such risk factors.

Because the NDDG8 and the Carpenter and Coustan 14 conversions of the original O’Sullivan and Mahan criteria3 are theoretical, the only way to determine which are most appropriate would be to re-create the original methodology (whole blood, Somogyi-Nelson) and run simultaneous samples against the newer plasma, glucose oxidase, or hexokinase methods. When this was carried out15, it appeared that the NDDG conversions were above the 95% confidence limits for all but the fasting sample, whereas the Carpenter and CousTable 35.3

Carpenter and Coustan Criteria for Gestational Diabetes Time Fasting 1 hour 2 hours 3 hours

Whole blood, Somogyi-Nelson 90 mg/dl 165 mg/dl 143 mg/dl 127 mg/dl

Plasma, glucose oxidase 95 mg/dl 180 mg/dl 155 mg/dl 140 mg/dl

If any two threshold values for glucose after a 100-g oral glucose challenge are met or exceeded, gestational diabetes is diagnosed. Source: Reference 14

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test only for gravidas age ≥30 years and younger women if risk factors are present.

Because the prevalence of gestational diabetes, like that of NIDDM, increases with advancing maternal age, using specific maternal age thresholds at which to pursue universal glucose challenge screening has been advocated by some11. Although a number of studies6,18 found that as many as 80% of women with gestational diabetes are age ≥25 years, the value of an age threshold depends on the characteristics of the population being investigated. For example, in an adolescent pregnancy program all gravidas are age 29 years and younger women if risk factors are present) would detect only 65% of cases of gestational diabetes. Such findings support the ADA’s recommendation1 that all pregnant women should be screened with a glucose challenge test.

Thresholds Subsequent research regarding the 50-g, 1-hour glucose challenge test has focused on the most appropriate thresholds and conditions for testing. Because no study, other than that of O’Sullivan et al.6, has included universal diagnostic testing, sensitivities reported by various studies should be considered as overestimates; there is always the possibility that cases of gestational diabetes existed at lower screening test values in these studies and were undetected. As laboratories changed from whole blood to plasma and adapted enzymatic methods of glucose analysis, it became necessary to extrapolate from O’Sullivan’s data10,12-13 to set screening test thresholds. While the ADA1 and ACOG11 recommend a threshold of 140 mg/dl for the 1-hour screen when plasma and enzymatic methods of analysis are used, studies using lower thresholds have demonstrated that 10% of individuals with gestational diabetes manifested screening tests between 130 and 139 mg/dl19,22.

GLUCOSE CHALLENGE TEST In 1973, O’Sullivan et al. suggested the use of a 50-g, 1-hour oral glucose challenge to screen for gestational diabetes6. Using venous whole blood samples and the Somogyi-Nelson technology, this group found that a threshold of 130 mg/dl was 79% sensitive and 87% specific for gestational diabetes in a population of 752 gravidas, all of whom also underwent the diagnostic 100-g, 3-hour OGTT. While sensitivity and specificity are the epidemiologic measures usually considered, the clinician is often most interested in positive and negative predictive accuracy. The positive predictive accuracy of a test is the likelihood of the presence of the condition being sought, given a positive screening test. For the O’Sullivan study, the positive predictive accuracy was 14% (15/109). The negative predictive accuracy, or the likelihood of normalcy given a negative screening test, was 99.4% (639/643). This means that 0.6% of individuals with normal screening tests had gestational diabetes. These two attributes of a screening test, unlike sensitivity and specificity, are highly dependent on the prevalence of the condition in the population. If the prevalence of gestational diabetes in O’Sullivan’s population had been 10% instead of 2.5%, the negative predictive accuracy would have decreased to 97.5%, meaning that 2.5% of individuals with 1-hour glucose values 33 years. These data suggest that, at least among high-risk individuals, glucose tolerance continues to decrease even in the mid-third trimester. It can be concluded from the foregoing studies that some, but not all, gestational diabetes can be diagnosed as early as the first half of pregnancy. However, early screening, if negative, requires repeat testing in the early third trimester to ensure adequate sensitivity. This retesting will inevitably increase the cost of the screening program. Therefore, evidence of a beneficial effect of early diagnosis of gestational diabetes (i.e., before 24-28 weeks) would be required before universal screening at the first prenatal visit as well as at 24-28 weeks should be recommended. Such evidence is currently lacking. Therefore, it may be most appropriate to reserve early screening for those with a particularly high likelihood of gestational diabetes. Such patients would include, among others, those with gestational diabetes in a previous pregnancy, who appear to have a 50% recurrence risk32-34.

Researchers have examined the possibility of using a challenge composed of mixed nutrients instead of the traditional pure glucose load. Their rationale was that a mixed meal more closely approximates the way in which people normally ingest nutrients and is more palatable than pure glucose. For example, the use of a plasma glucose determination 1 hour after a standard 600 kcal breakfast was compared with the 50-g challenge in a randomized crossover design in which 50 presumed normal subjects and 20 with known gestational diabetes were tested25. At a threshold of 100 mg/dl, sensitivity of the breakfast challenge was 96% and specificity was 74%. Using a threshold of 120 mg/dl at 1 hour after the breakfast would yield a sensitivity of only 75%. This test may be useful, particularly in patients who are unable to tolerate the usual glucose challenge. A 100 mg/dl threshold is recommended.

Timing of the Screening Test Because of the common recommendation that the glucose challenge be administered at 24-28 weeks gestation, a number of investigators have explored the effect of advancing gestation on screening test function. Hong et al.26 performed a cross-sectional study of 999 prenatal patients, administering the glucose screening test at the first prenatal visit. There was an increasing likelihood of gestational diabetes as pregnancy progressed, suggesting that the screening test performed early in pregnancy is likely to miss affected individuals (Table 35.4). Watson et al.27 performed a longitudinal study of 550 prenatal patients screened at 20, 28, and 34 weeks gestation. There was an average increase in the screening test result of 1.1±1.9 mg/dl per week. Nahum et al.28 found a significant increase in positive screening test results from the first to the early third trimester in 124 subjects who had serial testing. Gravidas with first trimester screening test results