THE YEAR IN DIABETES 2001
THE YEAR IN DIABETES 2001 Edited by
Ramón Gomis and Simon Page
CLINICAL PUBLISHING SERVICES OXFORD
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[email protected] © Clinical Publishing Services Ltd 2001 First published 2001 This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Clinical Publishing Services Ltd A catalogue record for this book is available from the British Library ISBN 0-203-01180-5 Master e-book ISBN
ISBN0953733963 (Print Edition) The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publisher do not accept any liability for any errors in the text or for the misuse or misapplication of material in this work. Commissioning Editor: Jonathan Gregory Project Manager: Rosemary Osmond
Preface
Research is the key to medical progress. Even if no-one doubts that this is true, doctors embroiled in the business of daily clinical practice do not devote the time needed to keep abreast of advances in fundamental and experimental medicine, as though these findings were nothing to do with them. Very often, public access to biomedical information makes the patient run straight to their doctor and ask why they are suffering from the illness concerned and about the latest treatments that may relieve their suffering. Putting it another way, the doctor is obliged not only to have the latest information about the illness, but also be capable of informing their client about the relevance of information transmitted by the general media and have an opinion about the future viability or non-viability of the options broadcast. Hence, the importance of commenting on clinical trials, advances and fundamental research in progress. Armed with this analysis and commentary, the reader will have the advantage over those with only partial or biased information. Another important point worth mentioning is that the complications of an illness have immense social impact, whether through their incidence, severity or the expense that they incur. No-one should wonder why diabetes, in terms of its incidence, the severity of its complnes for dealing with it. These guides are an invaluable aid for general practitioners and for specialists alike. Remember that cardiovascular complications, against a background of diabetes mellitus, dyslipidaemia, obesity and high blood pressure, call for a global approach and need to be studied from all angles. Consequently, it is important to establish clear guidelines that cannot be misinterpreted and that can be used for working efficiently on the diagnosis of diabetes mellitus and its treatment. Nor should we overlook the importance of diabetes and pregnancy. It is a field in which adequate treatment prevents much suffering. This treatment is within the reach of the clinic that is aware of the importance of diagnosing diabetes mellitus during the early stages of pregnancy and is prepared to use intensive treatment with the sole aim of maintaining glucose homeostasis and keeping fats within normal limits. In The Year in Diabetes, we have aimed to provide a gateway to the research published over the previous year, to assist you, the physician, in managing this condition in the most up-to-date and appropiate way. Ramon Gomis Simon Page
Contents
Part I
Contributors
vii
Preface R Gomis
iv
Acknowledgements
ix
Diabetes management guidelines 1.
Diabetes management guidelines according to the American Diabetes Association
2.
Criteria for diagnosing diabetes
3 43
Part II Clinical trials 3.
Clinical trials in the process of development
55
4.
Recent results of clinical trials
63
Part III Advances in type 1 diabetes mellitus 5.
Current status of type 1 diabetes mellitus
107
6.
Chronic complications of diabetes and endothelial dysfunction
120
7.
Management of diabetes mellitus
136
Part IV Insulin resistance: type 2 diabetes mellitus and obesity 8.
Type 2 diabetes mellitus and cardiovascular risk
156
9.
Diabetes and obesity
172
Part V Diabetes and pregnancy 10.
Diabetes and pregnancy
195
Part VI Diabetes research 11.
Diabetes research
217
List of abbreviations
239
vi
Index of papers reviewed
244
General index
252
Contributors
General Editors RAMÓN GOMIS, MD, Head of the Endocrinology and Diabetes Department, Clinic Hospital, Barcelona, Spain SIMON PAGE, MD FRCP, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom Editorial Coordinator ÀNGELS COSTA, MD, August Pi I Sunyer Institute of Biomedical Investigation, University Hospital Clinic, Barcelona, Spain Endocrinology and Diabetes Department, University Hospital Clinic, Barcelona, Spain EVA AGUILERA MARGARITA JANSÀ MONICA RECASENS GEMMA SESMILO OLGA SIMÓ MERCÈ VIDAL August Pi I Sunyer Institute of Biomedical Investigation (IDIBAPS), Barcelona, Spain SILVIA BARCELÓ CARMEN BENITO AIDA CABALLERO MARC CLARET HELENA COROMINOLA IMMA CORONADO ÀNGELS COSTA MARIA JOSÉ COVES MARTA E FABREGAT
viii
ELENA FERNÁNDEZ LILLIAM FLORES MÓNICA GUDAYOL CONXI MORA ROSA MORINIGO BELÉN NADAL ISABEL ROJAS
Acknowledgements
The editors would particularly like to acknowledge the work of Dr Àngels Costa in coordinating the compilation of The Year in Diabetes 2001, which owes much to her energy and efficiency. In producing this book, Dr Àngels Costa has shown exemplary dedication and efficiency. She has cleverly involved everyone in it and has elicited the best information from each contributor. Even in her youth and during the early stages of her brilliant professional career, her maturity, her achievements and the critical bases of her decisions gave her distinction. Without the dynamism of Dr Àngels Costa, the quality of the comments and speed of completion would probably not have been accomplished. In addition, by involving suitable people in the project, she has been able to select good references and the most promising tests and subjects for debate. In praising her work, we must not forget the collaborative efforts of her team of physicians, based at the Endocrinology and Diabetes Department of the Barcelona Clinic Hospital, who provided summaries and commentaries on the key papers. I doubt that few projects were planned as collectively as this one. We think that the reader will appreciate it and from a different perspective will appreciate the joint vision and the emphasis on balance, and will not set aside critical opinion. We shall welcome it. It only remains for us to congratulate and thank the publisher for their confidence in the Endocrinology and Diabetes Department of the Barcelona Clinic Hospital. The Editors
Part I Diabetes management guidelines
Diabetes management guidelines
Introduction The American Diabetes Association (ADA) is the USA’s leading non-profit health organization and it provides diabetes research, information and advocacy. The aim of the organization is to prevent and cure diabetes and to improve the lives of all people affected by diabetes. The ADA funds research, publishes scientific findings and provides information and other services to people with diabetes, their families, health care professionals and the public. The ADA is also actively involved in advocating for scientific research and for the rights of people with diabetes. The ADA regularly publishes its clinical practice recommendations in the January supplement of the journal Diabetes Care. Important themes this year include the ADA’s decision to follow the trend of evidence-based medicine and to appraise the scientific evidence supporting each of its recommendations. Amongst the 2001 recommendations are a series of innovative aspects that are worth pointing out. 1. An action plan for dealing with acute hyperglycaemic complications has been introduced. 2. The target blood pressure has been reduced to Cupples LA, Singer DE, Nathan DM, Schaefer EJ, Wilson PW. Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study. Diabetes Care 2000; 23: 669–74. 286 Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G. Hypoinsulinaemia, glucose intolerance and diminished B cell size in S6Kl-deficient mice. Nature 2000; 408: 994–7. 276 Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nature Med 2000; 6:278–82. 280 Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD and German MS. Expression of neurogenin-3 reveals an islet cell precursor population in the pancreas. Development200ty 127:3533–42. 278 Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343(4):230–8. 271 Shimomura H, Sanke T, Hanabusa T, Tsunoda K, Furuta H, Nanjo K. Nonsense mutation of the islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history. Diabetes 2000; 49: 1597–600. 288 Tawata M, Hayashi JI, Isobe K, Ohkubo E, Ohtaka M, Chen J, Aida K, Onaya T. A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic mutation for maternally inherited type 2 diabetes. Diabetes 2000; 49:1269–72. 287
251
Waeber G, Delplanque J, Bonny C, Mooser V, Steinmann M, Widmann C, Maillard A, Miklossy J, Dina C, Hani EH, Vionnet N, Nicod P, Boutin P, Froguel P. The gene MAPK8IP1 encoding islet-brain-1 is a candidate for type 2 diabetes. Nature Genet 2000; 24:291–5. 289
General Index
A abdominal obesity 237 and polycystic ovary syndrome 217 and risk of type 2 diabetes 222–3 see also obesity acarbose 120 clinical trials 75–6 STOP-NIDDM trial 70–1 ACE (angiotensin-converting enzyme) inhibitors 10, 121–2 renoprotective effect 34, 65–7, 68, 152 use in pregnancy 31 see also captopril; lisinopril; ramipril acesulphame K 15 Actrapid, comparison with insulin aspart 77–78 ADA see American Diabetes Association adenosine triphosphate see ATP adenovirus-induced hyperleptinaemia 224 adipocytes endocrinology of 191 effect of hyperleptinaemia 224 and resistin 191, 222 and thiazolidinediones 293–4 adipose tissue transplantation in lipodystrophic diabetes 294 ADMIT (Arterial Disease Multiple Intervention Trial) 104–5 adolescent type 1 diabetics 161–2 aetiology of diabetes 56–7 type 1 181–2 type 2 189 age, as risk factor in type 2 diabetes 5 albuminuria see mico-albuminuria; nephropathy; proteinuria alcohol 16
ambulatory blood pressure monitoring 148–9 use in adolescent type 1 diabetics 161–2 use in pregnancy 244–6, 264 American Diabetes Association (ADA) 1 diagnostic criteria 51–3, 208–10, 246–7, 265 amlodipine, in Irbesartan Type II Diabetic Nephropathy Trial 65–7 android obesity see abdominal obesity angiotensin II receptor antagonists 121–2 see also irbesartan angiotensin-converting enzyme inhibitors see ACE inhibitors anti-obesity drugs see orlistat; sibutramine antihypertensives and risk of type 2 diabetes 199–200 apolipoprotein E polymorphisms 286–7 Arterial Disease Multiple Intervention Trial (ADMIT) 104–5 aspartame 15 aspartic insulin see insulin aspart aspirin, use in peripheral vascular disease 25 asymptomatic bacteriuria 159–161 atheroma, role of endothelial dysfunction 191 atorvastatin, use in type 2 diabetics 107–10 ATP, role in insulin secretion 274–5 autoantibodies 181–2 and age of onset of type 1 diabetes 137–8 anti-insulin 142–3 in diagnosis of type of diabetes 136–7 lack in type 1 diabetes 129–31, 273–4, 295 autoantigens, presence in thymus 140–1 autoimmune diabetes 54 slowly progressing 134 autonomic neuropathy in adolescent type 1 diabetics 161– 2 and exercise 20 see also neuropathy 252
GENERAL INDEX
A-ZIP-F1 mice 294 B β cell antigens 181 presence in thymus 141–2 β cell replacement therapy see islet transplantation β cells function and oral insulin administration 100–3 conservation 137, 237 effect of glitazones 81–2 growth, and S6 kinase 1 (S6K1) 276–7 offloading 237 effect of thiazolidinediones 202–4 see also islet cell antibodies; islet cell differentiation; islet transplantation bacteriuria, asymptomatic 159–161 Bedford study 63, 72 beta blockers, and type 2 diabetes risk 199–200 β TC3 cells 288, 89 big babies 36, 39 and risk of type 2 diabetes 5 birth weight, and risk of type 2 diabetes 260–1 blood glucose levels, and alcohol 16 blood glucose meters 184 accuracy 169 use in screening 6 blood glucose monitoring 41–3 blood pressure 127–128 ambulatory monitoring in pregnancy 244–6, 264 effect of exercise 21 and nephropathy 33, 34 effect of orlistat 237 and risk of complications in type 2 diabetes 151–2 effect of weight loss 230 see also hypertension body mass index association with C-reactive protein 196– 7 and tumour necrosis factor-α 204–5 bovine insulin exposure, and type 1 diabetes 133–38, 182 brain, insulin signalling 225 breast feeding, and gestational diabetes 39 Bypass Angioplasty Revascularisation Investigation (BARI) 127, 147–48 C C-reactive protein 236 association with body mass index and diabetes 196–7
253
association with mortality 198–9 Ca21 signalling and insulin gene transcription 290–1 CABG see coronary artery bypass grafting Caesarian section, and gestational diabetes 36, 39 calcium channel blockers, renal effects 67 calcium signalling and insulin gene transcription 290–1 calpain-10 284–5, 296 Candesartan and Lisinopril Microalbuminuria Study 122 capillary blood glucose, use in screening 6 see also blood glucose meters captopril, renoprotective effect 65, 152 see also ACE inhibitors carbohydrate intake 14 cardiovascular disease risk 53 apolipoprotein E polymorphisms 287 association of hyperinsulinaemia with impaired fibrinolysis 194–5, 236 and C-reactive protein 197, 198–9, 236 anddiet 13–14 evaluation of 18 effect of exercise 21 hyperinsulinaemia cluster 200–1 effect of orlistat 214–5 in pre-diabetic state 201–2 effect of ramipril 92–3 in type 2 diabetes 189–190 and Von Willebrand factor 198–200 effect of weight loss 233–4 central obesity see abdominal obesity cerebral insulin signalling 225 cerebrovascular disease, progression after transplant surgery 156–7, 184 chemical-induced diabetes 56 childhood growth rate and risk of type 2 diabetes 260, 261 childhood onset diabetes immunology 135–6, 182 incidence 131–3 children, night-time insulin pump therapy 99–100 cholesterol intake 13–14 cholesterol levels and fat intake 13 effect of metformin-rosiglitazone combination 81 effect of niacin (ADMIT study) 104–5 as risk factor 5 see also dyslipidaemia; hyperlipidaemia; LDL cholesterol chromium deficiency 17 classification of diabetes 54–7
254
GENERAL INDEX
type 1 diabetes 129–131 White’s classification 254 combination therapy in type 2 diabetes 120 metformin and nateglinide 82–4 metformin and rosiglitazone 78–82 complications of diabetes acute 9–10, 42 association with blood pressure 151–2 asymptomatic bacteriuria 159–61 risk factors 119–21 for micro-angiopathy 153–4 risk of hyperglycaemia 157–59 social impact 3 see also autonomic neuropathy; nephropathy; neuropathy; peripheral neuropathy; peripheral vascular disease; retinopathy congenital anomalies in diabetic pregnancies 253–56 continuing care visits 8–9 continuous glucose monitoring 170, 184 continuous subcutaneous insulin infusion (CSII) 47–48, 120 comparison with MDI 92–4 use of insulin aspart 116–17 use in pregnancy 262–3, 264 see also insulin pumps corn syrup 14–15 coronary artery bypass grafting 127 BARI trial 147–48 coronary heart disease, progression after transplant surgery 156–7, 184 cows’ milk exposure, and risk of type 1 diabetes 137–38, 182 CSII see continuous subcutaneous insulin infusion cytokines 195–6 D Da Qing trial 63, 73 daclizumab, use in islet transplantation 271 DCCT see Diabetes Control and Complications Trial DECODE study, diagnostic criteria 53 dextrose 14–15 diabesity 227 Diabetes Care 3 Diabetes Control and Complications Trial (DCCT) 92, 127, 145–7, 182 effect of pregnancy on retinopathy 243–4, 264 Diabetes Prevention Program (DPP) 69–70
Diabetes Prevention Study (DPS) 72–73 Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) 139–40 DIABHYCAR study 67–68 diagnosis of diabetes 51–59, 209–9 ADA criteria 246–7, 265 role of HbA1c 171–3 WHO criteria 246–7, 265 in young adults 136–7 see also fasting plasma glucose; oral glucose tolerance test DiaMond project 131–3 diet 10–17 fat substitutes 48–49 fibre intake 15, 166–7, 184 role in prevention of type 2 diabetes 63, 72–3 very low-calorie 228, 229 see also lifestyle modification; medical nutrition therapy drug-induced diabetes 56 dyslipidaemia benefits of Mediterranean-type diet 178–80 and fructose 14 management 25–7 see also hyperlipidaemia; hypertriglyceridaemia E economic aspects of glycaemic control 173–4 educational level, and risk of metabolic syndrome 174–7 elderly people, and exercise 23 endogenous glucose production in type 2 diabetes 210–11 endothelial dysfunction 190 Epidemiology of Diabetes Complications (EDC) Study 141 Epidemiology of Diabetes Interventions and Complications (EDIC) Study 145–7, 182–3 erectile dysfunction, use of sildenafil 110–11 ethnic risk factors 5 for gestational diabetes 37 EURODIAB IDDM Complications Study 153–4, 183 exercise 18–23 classification of intensity 19 role in gestational diabetes 39 effect on insulin absorption 47 patient evaluation 18–21 role in peripheral vascular disease 25 role in prevention of type 2 diabetes 63, 73, 167–9 see also lifestyle modification
GENERAL INDEX
F family history, as risk factor 7 Fasting Hyperglycaemia Study (Oxford) 73 fasting plasma glucose (FPG) role in diagnosis 51–3, 58, 59, 208–9 role in screening 5–6, 246–7, 264–5 fat intake 13–14 fat substitutes 48–49 fibrates 26–7 fibre intake 15 benefits 166–7, 184 fibrinolysis effect of exercise 22 and hyperinsulinaemia 194–5, 236 Finnish Diabetes Prevention Study 119 Food and Drug Administration (FDA) 15 foot care 23–5 foot ulceration, risk factors 155–6 FPG see fasting plasma glucose Framingham Offspring Study 194–5, 236, 286–7 frequency of clinic visits 8 fructosamine analysis 41 fructose 14 fruit juice, use as sweetener 14–15 G gabapentin, use in neuropathy 123 GAD see glutamic acid decarboxylase gastric reduction surgery 12 gene therapy in type 1 diabetes 282 genetic causes of diabetes 57 genetic factors in age of onset of type 1 diabetes 135–6 genetic studies 296 apolipoprotein E polymorphisms 286–7 calpain-10 284–5 islet-1 gene mutation 288–9 MAPK8IP1 gene 289–90 mitochondrial DNA mutation 287–8 PPAR-γ polymorphism 282–4 SHIP2 285–6 gestational diabetes 36–39, 120 comparison of glyburide with insulin 111–13 and congenital anomalies 255–58 and glucokinase mutations 247–49 use of insulin lispro 96–7 post-partum reclassification 246–7, 264 risk of type 2 diabetes 5, 202 see also pregnancy and diabetes glitazones see pioglitazone;
255
rosiglitazone; troglitazone glucagon levels, in LADA-type diabetes 134 glucokinase mutations 247–9, 265 glucose intolerance association of hyperinsulinaemia with impaired fibrinolysis 194–5 see also glucose tolerance; impaired glucose tolerance; oral glucose tolerance test glucose metabolism, intracellular signalling 290–1 glucose meters 184 accuracy 169 use in screening 6 glucose tolerance effect of dietary interventions 232 effect of orlistat 213–14 see also glucose intolerance; impaired glucose tolerance; oral glucose tolerance test glucose tolerance test see oral glucose tolerance test α-glucosidase inhibitors, STOP-NIDDM trial 70–1 glutamate, role in insulin secretion 274–6 glutamic acid decarboxylase (GAD) 181, 182 use in classification of type 1 diabetes 129–31 glutamic acid decarboxylase antibodies, and prediction of need for insulin 136–7 glyburide, use in gestational diabetes 111–12 glycaemic control blood glucose monitoring 39–41 continuous 170, 184 economic considerations 173–4 effect of exercise 21 and medical nutrition therapy 11 and nephropathy 34 pre-conception care 30, 31 and pre-eclampsia 249–51, 264 and risk of complications 157–58, 162, 182–3 see also poor control; postprandial glycaemic control glycaemic targets 6, 7 glycosylated haemoglobin see HBA1c glycoslyated serum proteins 41 growth hormone, and diabetic retinopathy 114 growth hormone-binding protein 205–208 guidelines 3, 5–49 diagnostic see diagnosis of diabetes H
256
GENERAL INDEX
haemostasis, and hyperinsulinaemia 194–5 HBA1c 41 effect of postprandial glycaemic control 85–7 role in diagnosis 171–2 health care expenses, and glycaemic control 173–4 hepatitis C and prevalence of type 2 diabetes 197–199 hepatocyte nuclear factor 1-α see HNF l α gene HLA type and diabetes 135–6, 181 HNF-l α gene, and MODY 273–4, 295–6 homocysteine, link with vascular disease 193–4, 236 honey 14–15 Hoorn study 190, 198–199, 236 diagnostic criteria 52–3 HOPE study 94–5, 121 hospital admission, guidelines 41–3 human islets, in vitro cultivation 277–9 see also islet transplantation hyperglycaemia and risk of complications 157–9 and risk of congenital anomalies in diabetic pregnancies 255–8 see also glycaemic control hyperglycaemia, non-ketotic hyperosmolar 42 hyperhomocysteinaemia 193–4, 236 hyperinsulinaemia association with impaired fibrinolysis 194–5, 236 and polycystic ovary syndrome 217 hyperinsulinaemia cluster and cardiovascular disease risk 200–1 hyperkalaemia 17 hyperleptinaemia, adenovirus-induced 224 hyperlipidaemia effect of exercise 21 and interleukin 6 gene polymorphism 195–6 see also cholesterol; dyslipidaemia; hypertriglyceridaemia hyperosmolar hyperglycaemia, non- ketotic 42 hypertension 10, 127–8 effect of exercise 21 and nephropathy 34 in pregnancy 31, 244–6, 264 see also pre-eclampsia; pregnancy- induced hypertension and risk of complications in type 2 diabetes 151–2 as risk factor 3 white coat 148–9 see also blood pressure Hypertension Optimal Therapy Trial 152
hypertriglyceridaemia, management 26–7 see also dyslipidaemia; hyperlipidaemia hypocaloric diet, advantages 12 hypoglycaemia 42, 47 and alcohol consumption 16 I IB-1 (islet-brain-1) 289–90 idiopathic diabetes 54–5, 129–31 IFG see impaired fasting glucose IGT see impaired glucose tolerance illness, intercurrent 9 immunomediated diabetes 54 see also autoantibodies; autoimmune diabetes immunosuppressive regimens 271, 295 impaired fasting glucose (IFG) 6, 57 impaired glucose tolerance (IGT) 6, 57 use of acarbose (STOP-NIDDM trial) 70–1 use in diagnosis 51–3 effect of lifestyle modification 74–5 effect of obesity 221 risks 190–1 see also glucose intolerance; glucose tolerance; oral glucose tolerance test impotence see erectile dysfunction in vitro islet cultivation human 277–8 mouse 280–1 incidence of type 1 diabetes 183 in childhood 131–3 inhaled insulin 105–6, 121 initial visit 7–8 injection sites 46 injection technique 46 inpatient care, guidelines 41–3 insulin use in gestational diabetes 39 oral administration 100–3 production in mouse liver cells 291–3 insulin action, effect of weight fluctuations 220–1, 237 insulin aspart 84–5 comparison with Actrapid 79–80 use in CSII 116–7 insulin autoantibodies 142–3 see also autoantibodies; bovine insulin exposure
GENERAL INDEX
insulin gene transcription 290–1 insulin glargine 87–9 insulin inhalation 105–6, 121 insulin injection technique 46 insulin-like growth factor 1 (IGF-1), and diabetic retinopathy 114, 115, 122 insulin lispro 120 comparison of CSII with MDI 92–4 use in gestational diabetes 96–7 and retinopathy in pregnancy 259–60 trial of multiple injection regimen using lispro HM 97– 9 insulin mixtures 45 insulin mRNA, and PDX-1 290–1 insulin pens 45–6 insulin preparations 44 insulin promoter factor 1 (PDX-1) 290–3 insulin pump therapy use in children 99–100 use in pregnancy 262–3, 264 see also continuous subcutaneous insulin infusion insulin regimens, study in type 2 diabetes 112–13 insulin resistance 44–5, 69 and apolipoprotein E polymorphisms 286–7 estimation in type 1 diabetics 141 effect of exercise 21 in LADA-type diabetes 134, 182 and lipodystrophy 294 in muscle tissue 235 and obesity 237 in pathogenesis of type 2 diabetes 210–11 in pre-diabetic state 201–2 effect of statins 107–10 effect of troglitazone 202–4 role of tumour necrosis factor-oc 204–5 insulin secretion effect of weight fluctuations 220–1, 239 role of mitochondrial glutamate 274–6 insulin secretory dysfunction, in pathogenesis of type 2 diabetes 210–11 insulin sensitivity, and SHIP2 285–6 insulin signalling, role in central nervous system 225 insulin storage 45 insulin syringes 45 insulin upstream factor 1 (PDX-1) 290–3 intensive insulin therapy 11 comparison of CSII with MDI 92–4 and risk of microvascular complications 145–7 see also continuous subcutaneous insulin infusion;
257
insulin pump therapy intercurrent illness, management 9 interleukin 6 197 gene polymorphism 195–6 irbesartan Irbesartan Diabetic Nephropathy Trial (IDNT) 121–2 Irbesartan Microalbuminuria Intervention trial 122 Irbesartan Type II Diabetic Nephropathy Trial 65–7 islet cells antibodies 181–2 use in screening 139 see also autoantibodies differentiation of 278–9 see also β cells islet transplantation 44, 271–2, 292, 295 in vitro human islet cultivation 277–8 in vitro mouse islet cultivation 280–1 islet-1 gene mutation 278–9 islet-brain-1 (IB-1) 289–90 islets, in vitro cultivation 277–8, 280–1 isoprostane production 158–9 K ketoacidosis 42 riskinCSII 262–3, 264 ketones, urinary 40–1 kidney transplantation 43, 183–4 and progression of macrovascular disease 156–7 L laboratory evaluation 8, 9 large babies 36, 39 as risk factor for type 2 diabetes 5 laser treatment of retinopathy 36 latent autoimmune diabetes of adults (LADA) 134, 183 LDL (low density lipoprotein) cholesterol 25 and fat intake 13 see also cholesterol 191, 205–208, 225 leptin effect of hyperleptinaemia on adipocytes 224 and tumour necrosis factor-α 204–5 life style modification 10 Diabetes Prevention Program (DPP) 69–70 Diabetes Prevention Study (DPS) 72–3 effect of increased dietary fibre intake 166–7, 184 in management of type 2 diabetes 227–9 in prevention of type 2 diabetes 119 smoking cessation 165–6, 183
258
GENERAL INDEX
see also diet; exercise lipid abnormalities interleukin 6 gene polymorphism 195–6 see also cholesterol; dyslipidaemia; hyperlipidaemia; hypertriglyceridaemia lipid levels dietary manipulation 230–2 effect of niacin (ADMIT study) 104–5 lipoatrophy and surgical implantation of adipose tissue 294 and thiazolidinediones 293–4 lipodystrophic diabetes 294 lipohypertrophy, effect on insulin absorption 47 lisinopril, Candesartan and Lisinopril Microalbuminuria Study 122 lispro insulin see insulin lispro liver cells, effect of PDX-1 291–3 losartan (RENALL study) 122 low birth weight, health risks 260–1 M macrosomia, fetal 5, 36, 39 macrovascular complications effect of transplant surgery 184 and glycaemic control 157–8 progression after transplant surgery 156–7, 184 macular oedema 36 magnesium deficiency 17 Malmo study 63, 73 Malmohus study 63, 73 maltose 15 management of diabetes 1, 5–49 mannitol 15 MAPK8IP1 gene 289–90, 296 maternally inherited diabetes 287–8 maturity onset diabetes of the young (MODY) 247, 265 prevalence of MODY-3 273–4 study of Spanish families 272–3, 295 medical history 7, 8 medical nutrition therapy (MNT) 6, 10–17 Mediterranean -type diet, benefits 178–80 metabolic syndrome, relationship to educational level 174– 7 metformin combination with nateglinide 83, 84 combination with rosiglitazone 78–82
comparison with acarbose 75–6 Diabetes Prevention Program (DPP) 69–70 mechanism ofaction 78 use in polycystic ovary syndrome 216–17 microalbuminuria 10, 32–4 in adolescent type 1 diabetics 161–3 effect of pregnancy 243–4 see also nephropathy microangiopathy, and C-reactive protein 197 MICRO-HOPE substudy 94–5, 121 micronutrients 17 microvascular complications and glycaemic control 157–8, 182–3 effect of intensive therapy 145–7 effect of pregnancy 243–4, 264 effect of ramipril 94–5 risk factors 153–4 see also autonomic neuropathy; nephropathy; neuropathy; peripheral neuropathy; retinopathy minerals 17 MIRKO mice 235 mitochondrial DNA mutations 287–8 mitochondrial glutamate, role in insulin secretion 274–6 mitochondrial uncoupling proteins 226–7 MNT see medical nutrition therapy Modified Diet in Renal Disease Study 12 MODY see maturity onset diabetes of the young mortality, effect of weight loss 232–5 mouse islets, in vitro cultivation 280–1 multiple daily injection (MDI) comparison with CSII 92–4 trial of insulin lispro HM 97–9 muscle tissue, insulin resistance 235 myocardial infarction, Bypass Angioplasty Revascularisation Investigation 147–8 N nateglinide 120 clinical trial 82–4 National Cholesterol Education Program (NCEP) 13 NAVIGATOR trial 120 nephropathy 10, 128 and angiotensin II receptor blockers 121–2 association with pregnancy-induced hypertension and pre-eclampsia 249, 250, 264 and exercise 20 effect of intensive therapy 145–7
GENERAL INDEX
Irbesartan Type II Diabetic Nephropathy Trial (IDNT) 65–7 management 32–4 and pregnancy 32 and protein intake 12–13 effect of ramipril 94 renoprotective effect of ACE inhibitors 65–7, 68, 121, 152 role of transforming growth factor-β (TGF-β) 154–5 see also microalbuminuria; microangiopathy; proteinuria nerve growth factor (NGF) 106–7 NES2Y cells 290–1 neurogenin-3 278–9 neuropathy 123 andexercise 20 andpregnancy 32 use of recombinant nerve growth factor 106–7 see also autonomic neuropathy; peripheral neuropathy niacin, effect on lipid levels (ADMIT study) 104–5 nicotine dependency see smoking; smoking cessation NIDDM-1 284–5, 296 nifedipine, renal effects 67 night-time insulin pump therapy, use in children 99–100 NIRKOmice 225 nitric oxide production 158–9 non-insulin dependant diabetes see type 2 diabetes non-ketotic hyperosmolar hyperglycaemia 42 NPH insulin, comparison with insulin glargine 87–9 nurse-led counselling, role in smoking cessation 165, 166, 183 nutrition see diet; medical nutrition therapy nutritive sweeteners 14–15 O obesity 11, 221 effect of exercise 22 and fat intake 14 and growth hormone secretion 207–8 effect of hyperleptinaemia on adipocytes 224 and insulin resistance in muscle 235 optimal diet in type 2 diabetes 230–2 refractory 12 and resistin 222 as risk factor 5 and type 2 diabetes 191, 237 see also abdominal obesity; weight reduction
259
obesogenic environment 227 octreotide, use in diabetic retinopathy 114–15, 122–3 OGTT see oral glucose tolerance test oleic acid diet, benefits 178–80 Olestra 49 oral glucose tolerance test (OGTT) use in diagnosis 51–3, 58, 59, 139–40, 208–9 of gestational diabetes 38 use in identifying MODY genotypes 273 use in screening 5–6, 246–7 oral hypoglycaemics and pregnancy 30 risk of hypoglycaemia 116–16 see also acarbose; metformin; phenformin; repaglinide; tolbutamide oral insulin administration 100–3 orlistat 191, 237 effect on cardiovascular disease risk 214–15 effect on glucose tolerance 213–14 oxidative stress 193 P pancreatic and duodenal homeobox factor 1 (PDX-1) 290– 3 pancreatic β cells see β cells; islet cells pancreatic transplantation 43–4, 183–4 and progression of macrovascular disease 156–7 effect on retinopathy 149–51 see also islet transplantation pancreatitis risk, role of fat intake 13 pathogenesis of type 1 diabetes 139, 140 of type 2 diabetes 210–11 patient self-monitoring see self-monitoring of blood glucose PDX-1 (pancreatic and duodenal homeobox factor 1) 290– 3 percutaneous transluminal coronary angioplasty (PCTA) 147–8 perinatal morbidity and mortality 251–5 peripheral neuropathy 20, 24 see also neuropathy peripheral vascular disease (PVD) evaluation 18, 24 management 25 progression after transplant surgery 156–7, 184
260
GENERAL INDEX
peroxisomeproliferator-activated receptors (PPARs) 293, 296 polymorphism 282–4 phenformin, use in impaired glucose tolerance 63 phenofibrate 26–7 photocoagulation 36 physical activity see exercise physical examination at initial visit 7–8 at continuing care visits 9–10 offeet 23–4 Pima Indians effects of weight fluctuation 220–1, 237 study of diagnostic criteria 51–3 pioglitazone 204, 117–8 plasma lipids see lipid levels polycystic ovary syndrome 37 use of metformin 216–17 polyneuropathy 123 andexercise 20 use of recombinant nerve growth factor 106–7 see also neuropathy polyols 15 polyunsaturated fat intake 13 poor control use of continuous subcutaneous insulin infusion 48 indications for hospital admission 42 see also glycaemic control post-prandial glycaemic control 63–4, 77–8, 120 and HbA1c 85–7 use of nateglinide 82–4 potassium intake 17 PPARs (peroxisome proliferator-activated receptors) 293, 296 polymorphism 282–4 pre-conception care 29–32 see also pregnancy pre-diabetes and cardiovascular disease risk 201–3 risk of stillbirth and perinatal death 251–3 see also impaired glucose tolerance pre-eclampsia association with severity of diabetes 253–5, 263–4 and glycaemic control 249–51, 264 risk in gestational diabetes 36 screening 244–6, 264 pre-gestational diabetes, risks of adverse neonatal outcome and pre-eclampsia 253–5 pregnancy 3, 55, 56, 120
ambulatory blood pressure monitoring 244–6, 264 congenital anomalies 255–8 continuous subcutaneous insulin infusion 48, 262–3, 264 and insulin lispro 259–60 medical nutrition therapy 17 effect on microvascular complications 243–4, 264 pre-eclampsia risk and glycaemic control 249–51 preparation for 29–32 risk of pre-diabetes 251–3 risk of pre-gestational diabetes 253–5 screening for retinopathy 36 see also gestational diabetes pregnancy-induced hypertension and glycaemic control 249–51 screening for 244–6, 264 prevention of type 2 diabetes 119 Diabetes Prevention Study (DPS) 72–3 Diabetes Prevention Program (DPP) 69–70 role of exercise 167–8 role of orlistat 213–14 STOP-NIDDM trial 70–1 PRIME study 121 protective mechanism loss 20 protein intake 12–13 restriction in nephropathy 10 proteinuria 33 in pregnancy, neonatal outcome 254, 255, 263 see also microalbuminuria; nephropathy Q Q310X mutation 288–9, 296 questionnaires, role in screening for diabetes 6 R racial risk factors 5 for gestational diabetes 37 ramipril 121 DIABHYCAR study 67–8 HOPE and MICRO-HOPE studies 94–5 see also ACE inhibitors recombinant adenoassociated virus (rAAV), use in gene therapy 282 recombinant human nerve growth factor 106–7, 123 refractory obesity 12 see also abdominal obesity; obesity; weight reduction renal transplantation 43, 183–4 and progression of macrovascular disease 156–7
GENERAL INDEX
RENALL study 122 repaglinide 89–92, 115–16, 120 resistin 191, 222, 225 retinal examination 10 retinopathy association with pregnancy-induced hypertension and pre-eclampsia 249, 250, 264 and glycaemic control 183 and insulin lispro in pregnancy 259–60 effect of intensive therapy 145–7 use of octreotide 114–15, 122–3 effect of pancreas and kidney transplantation 149–51 effect of pregnancy 243–4, 264 risks of exercise 18, 19 screening 35–6 effect of transplant surgery 183–4 risk factors for asymptomatic bacteriuria in women 160, 161 C-reactive protein 197, 198–9, 236 for complications of diabetes 119–20 for foot ulceration 155–6 for gestational diabetes 37 hyperhomocysteinaemia 193–4, 236 hyperinsulinaemia cluster 200–1 low cardio respiratory fitness 167–8 for microvascular complications 153–4 for type 2 diabetes 5, 6, 58, 72 Von Willebrand factor 198–9 rosiglitazone 204 combination with metformin 78–82 mechanism of action 78 effect on resistin levels 222 side effects 81 S S6 kinase 1 (S6K1) 276–7 saccharin 15 San Antonio Heart Study 190–1 saturated fat intake 13–14 screening for albuminuria 33–4 for diabetes 58, 59 type 2 5–6 role of fasting blood glucose 208–9 for gestational diabetes 37–8 role of glucose tolerance test 208–9 use of islet cell antibodies 139 for pregnancy induced hypertension 244–6, 264 for retinopathy 35–6 for risk of foot ulceration 155–6
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see also diagnostic criteria self-monitoring of blood glucose (SMBG) 6, 40 accuracy of glucose meters 169 SHIP2 (SH2 domain-containing inositol 5- phosphatase) and insulin sensitivity 285–6 SIA (single-chain insulin analogue), use in gene therapy 282 sibutramine 191, 217–20, 238 sildenafil 110–11 simvastatin 107–10 single-chain insulin analogue (SIA), use in gene therapy 282 sirolimus, use in islet transplantation 271 SMBG see self-monitoring of blood glucose smoking 28– 9 smoking cessation 165–6, 183 socio-economic status, and risk of metabolic syndrome 174–7 sodium intake 15–16 somatostatin, use in diabetic retinopathy 114, 115 sorbitol 15 standards of care 6–10 statins use in hypertriglyceridaemia 27 use in type 2 diabetics 107–10 stem cells 279, 292 use in in vitro islet cultivation 280–1 stillbirth risk and pre-diabetes 251–3 Stockholm Diabetes Intervention Study 146 STOP-NIDDM trial 70–1 sucralose 15 sucrose 14 sugar alcohols 15 sugar intake 14 sulphonylureas, risk of hypoglycaemia 115–16 surgical treatment of obesity 12 Swedish Multimorbidity Study 214–15 sweeteners 14–15 syndrome X 197 T tacrolimus, use in islet transplantation 271 âTC3 cells 288, 289 TGF-β (transforming growth factor-β1) 152, 154–5 thiazide diuretics and type 2 diabetes risk 199–200 thiazolidinediones 69–70, 202–4 actions in mice with lipoatrophy 293–4 and resistin 222 see also pioglitazone
262
GENERAL INDEX
thymus, antigen-presenting cells 140–1 TNF-α see tumour necrosis factor-α tobacco addiction see smoking; smoking cessation tolbutamide, use in impaired glucose tolerance 63, 73 transforming growth factor-β1 (TGF-β1) 152, 154–5 transplant surgery 43–4, 183–4 adipose tissue transplantation in lipodystrophic diabetes 294 islet transplantation 271–2 and progression of macrovascular disease 156–7 effect on retinopathy 149–51 treatment aims 6, 7 tricyclic antidepressants, use in neuropathy 123 triglyceride levels and fat intake 13 effect of niacin (ADMIT study) 104–5 as risk factor 5 see also hypertriglyceridaemia troglitazone 69–70, 202–4 tumour necrosis factor 197 tumour necrosis factor-oc receptor 2 gene polymorphism 204–5 24 hour blood pressure measurement see ambulatory blood pressure monitoring type 1 diabetes in adolescents 161–2 aetiology 181–2 and age of onset 135–6 asymptomatic 139–40 autoantibody negative 129–31, 273–4, 295 differences between adult and childhood onset 135–6 andexercise 22 gene therapy 282 incidence 181 inchildhood 131–3 and insulin resistance 141 and medical nutrition therapy 11 pathogenesis 139, 140 effects of pregnancy 243–4 prevalence of MODY-3 273–4, 295 prevalence of white coat hypertension 148–9 risk factors for micro-angiopathy 153–4 screening for retinopathy 35 urine ketone determination 40–1 type 1B diabetes 129–31 type 2 diabetes 55 aetiology 189 and antihypertensives 199–200 association with hepatitis C 197–8
association with weight at birth 260–1 benefits of exercise 167–9 benefits of Mediterranean-type diet 178–80 blood pressure and risk of vascular complications 151– 3 and calpain-10 284–5 cardiovascular disease risk 189–90, 200–1, 236 classification 189 and congenital anomalies 255–8 and diet 166–7, 184, 230–2 and exercise 21–3 and hyperhomocysteinaemia 193–4, 236 life style modification 227–9 and medical nutrition therapy 12 morbidity and mortality 119 and obesity 222–3, 237 see also abdominal obesity pathogenesis 210–11 and PPAR-γ polymorphism 282–4 prevention see prevention of type 2 diabetes risk factors 5, 6, 58, 72 screening for 5–6 screening for retinopathy 35 U ultralente insulin, use in type 2 diabetes 112–13 uncoupling proteins (UCPs) 226–7 United Kingdom Prospective Diabetic Study (UKPDS) 127, 128, 151–2 urinalysis 33–4 role in glycaemic control 40–1 urinary albumin excretion levels, and white coat hypertension 148, 149 urine ketone determination 40–1 V vascular disease role of hyperhomocysteinaemia 193–4, 236 see also cardiovascular disease risk; peripheral vascular disease very low-calorie diets 228, 229 Viagra (sildenafil) 110–11 viruses, role in aetiology of type 1 diabetes 182 visceral adiposity see abdominal obesity vitamins 17 vitreoretinal surgery 36 VLDL (very low-density lipoprotein) cholesterol, and fat intake 13
GENERAL INDEX
Von Willebrand factor, association with mortality 198–9, 236 W weight fluctuations, effects on insulin action and secretion 220–1, 237 weight reduction 221 advantages 12 fat substitutes 48–9 in gestational diabetes 39 effect on mortality 232–5 use of orlistat 191, 213–15, 237 use of sibutramine 217–20, 238 role of uncoupling proteins 226–7 see also abdominal obesity; medical nutrition therapy; obesity white coat hypertension, prevalence 148–9 Whitehall study 63, 72 World Health Organization (WHO) criteria for diagnosis 51–3, 208–9, 246–7, 265 White’s classification of diabetes 256 X xylitol 15
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