Textbook of Diabetes (eBook)

Richard I. G. Holt, Clive Cockram, Allan Flyvbjerg, Barry J. Goldstein (Herausgeber)

eBook Download: PDF

2016 | 5. Auflage
John Wiley & Sons (Verlag)
978-1-118-92487-7 (ISBN)

Infos

Now in its fifth edition, the Textbook of Diabetes has established itself as the modern, well-illustrated, international guide to diabetes. Sensibly organized and easy to navigate, with exceptional illustrations, the Textbook hosts an unrivalled blend of clinical and scientific content. Highly-experienced editors from across the globe assemble an outstanding set of international contributors who provide insight on new developments in diabetes care and information on the latest treatment modalities used around the world. The fifth edition features an array of brand new chapters, on topics including:

• Ischaemic Heart Disease
• Glucagon in Islet Regulation
• Microbiome and Diabetes
• Diabetes and Non-Alcoholic Fatty Liver Disease
• Diabetes and Cancer
• End of Life Care in Diabetes

as well as a new section on Psychosocial aspects of diabetes.

In addition, all existing chapters are fully revised with the very latest developments, including the most recent guidelines from the ADA, EASD, DUK and NICE.  

Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Via the companion website, readers can access a host of additional online materials such as:

• 200 interactive MCQ's to allow readers to self-assess their clinical knowledge
• every figure from the book, available to download into presentations
• fully searchable chapter pdfs

Once again, Textbook of Diabetes provides endocrinologists and diabetologists with a fresh, comprehensive and multi-media clinical resource to consult time and time again.

Richard I.G. Holt, MA, MB BChir, PhD, FRCP, FHEA
Professor in Diabetes & Endocrinology, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK.

Clive S. Cockram, MB BS, BSc, MD (Lond), FRCP, FRACP, FHKAM (Med)
Emeritus Professor of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.

Allan Flyvbjerg, MD, DMSc
Professor of Clinical Endocrinology and Chair, Department of Endocrinology and Internal Medicine, The Medical Research Laboratories, Aarhus University Hospital - Aarhus University, Aarhus, Denmark.

Barry J. Goldstein, MD, PhD, FACP, FACE
Therapeutic Area Head, Diabetes and Obesity, Vice President, Clinical Research, Metabolism, Merck Research Laboratories, Rahway, NJ, USA.

Inhalt

Textbook of Diabetes 3
Contents 7
List of Contributors 10
Preface to the Fifth Edition 16
List of Abbreviations 17
About the Companion Website and Companion Digital Edition 20
1 Diabetes in its Historical and Social Context 21
1 The History of Diabetes Mellitus 23
Ancient times 24
The 17th and 18th centuries 24
The 19th century 26
Clinical diabetes in the 19th century 28
The 20th century 29
Discovery of insulin 30
The postinsulin era 32
Causes and natural history of diabetes 32
Chronic diabetic complications 33
Physiology 34
Management of diabetes 35
Insulin 37
Oral antidiabetes agents 37
Glucose control and treatment targets 37
Diabetic complications 38
Diabetic ketoacidosis 38
Diabetic pregnancy 39
Delivery of care for people with diabetes 40
References 40
Further reading 42
Websites 42
Discovery of insulin 42
Archives 42
2 Classification and Diagnosis of Diabetes 43
Introduction 43
Definition 43
Classification of diabetes 44
Methods and criteria for diagnosing diabetes [5,6] 44
Glycated hemoglobin (HbA1c) for diagnosis of diabetes 44
Type 1 diabetes (T1DM) [5,6] 46
Type 2 Diabetes (T2DM) 46
Other specific types 47
Gestational diabetes (GDM) 47
Intermediate hyperglycemia or impaired glucose regulation (prediabetes) 48
Conclusion 48
References 48
3 Epidemiology of Type 1 Diabetes 49
Introduction 49
Occurrence of T1DM by age, sex, place, and time 50
Occurrence of T1DM by age 50
Incidence by sex 51
Incidence by country 51
Trends in incidence over time 52
Variation in incidence within countries, including byethnic group 53
Seasonal variation in diagnosis of T1DM 54
Familial clustering and twin studies 54
Environmental risk factors for T1DM: clues from epidemiological studies 55
Specific putative environmental factors 56
Mortality 59
Conclusions 60
Acknowledgments 60
References 60
4 Epidemiology of Type 2 Diabetes 63
Introduction 63
Risk factors for T2DM 64
Recent emerging risk factors 65
Sugar-sweetened beverages 65
Decreased sleep 65
Depression and treatment of depression 65
Drug-induced metabolic changes 65
Environmental toxins 65
Low birthweight and fetal malnutrition 65
Maternal obesity, maternal hyperglycemia, and other factors in early development 65
Methodological issues in the epidemiology of T2DM 66
Effects of changes in the definition of diabetes 66
Regional and ethnic patterns of T2DM worldwide 67
Africa 68
North America and the Caribbean 69
Central and South America 70
Europe 70
Southeast Asia 72
The Middle East and North Africa 73
Western Pacific region 73
Impact of diabetes 76
Mortality and morbidity 76
Healthcare burden and economic costs 76
Prevention of T2DM 77
Conclusions 80
Acknowledgments 80
References 80
5 The Global Burden of Diabetes 85
Introduction 85
Distribution 86
Major burdens 87
Acute and chronic disease complications 87
Health utilization patterns 88
Disability 89
Psychosocial burdens 89
Mortality 90
Economic costs of diabetes 91
Types of costs 91
Cost appraisal methods 91
Individual-level cost drivers 98
Country-level cost patterns 98
Changing trends in costs 99
Gaps and future directions 100
References 100
2 Normal Physiology 105
6 Islet Function and Insulin Secretion 107
Introduction 107
Islet structure and function 107
Islet anatomy 107
Intra-islet interactions 108
Insulin biosynthesis and storage 108
Regulation of insulin secretion 112
Nutrient-induced insulin secretion 112
Regulation of insulin secretion by non-nutrients 116
Conclusions 120
References 120
7 Glucagon in Islet and Metabolic Regulation 123
Introduction 123
a-Cell anatomy and development 123
Proglucagon gene transcription, translation and peptide processing 124
Regulation of a-cell secretion 125
Glucagon actions: hepatic glucose and lipid metabolism 126
Non-hepatic effects of glucagon 128
Other ??????-cell peptides 128
Abnormalities of glucagon secretion and action in diabetes 129
Pharmacology based on glucagon action 130
References 131
8 Mechanism of Insulin Action 134
Introduction 134
Insulin receptor 135
Introduction 135
Structure and function 135
The insulin binding site 136
Regulation of the InsR kinase 137
Systemic deletion of the insulin or type 1 IGF receptor 137
Tissue-specific inactivation of the insulin receptor 137
IRS-proteins coordinate insulin and insulin-like growth factor signaling 138
Structure and function 138
Systemic inactivation of IRS genes 140
Inactivation of IRS in liver 141
Inactivation of IRS in muscle 141
PI3K?AKT cascade 141
AKT?mTORC1 cascade 142
AKT?mTORC2?AKT cascade 143
AKT?FOXO cascade 144
Heterologous regulation and dysregulation of the insulin and insulin-like growth factor signaling cascade 145
Concerted regulation of proximal insulin signals 145
Transcriptional control of IRS1 145
Multiple factors regulate IRS2 transcription 145
miRNA-mediated post-transcriptional regulation 146
Post-translational regulation of insulin and insulin-like growth factor signaling 146
Degradation of the IRS-proteins 146
Multisite Ser/Thr-phosphorylation of IRS-proteins 147
Modulation of insulin signaling by protein and lipid phosphatases 148
IRS2 as a gateway to b-cell function 149
References 149
9 Control of Weight: How Do We Get Fat? 153
Introduction 153
Genetic factors 153
Heritability of obesity 153
Monogenic obesity 153
Common obesity “susceptibility” genes 153
“Missing heritability”—epigenetics and intrauterine imprinting 154
Environmental factors 154
Sedentary lifestyle 154
Energy intake—quantity of food consumed 155
Dietary composition: sugar versus fat 155
Calorically (sugar) sweetened beverages 155
Eating out and portion size 155
Snacking 155
Eating patterns 156
Advertising 156
Globalization and government regulation 156
Sleep patterns 156
Medications and toxins 156
Medications 156
Toxins and endocrine disruptors 157
Neuroendocrine and behavioral regulation of energy homeostasis and the gut microbiome 157
Neuroendocrine and behavioral pathways 157
Gut microbiome 157
Conclusions 158
References 158
3 Pathogenesis of Diabetes 161
10 Autoimmune Type 1 Diabetes 163
Introduction 163
Epidemiology 164
Etiopathophysiology 164
Etiology 165
Genetic etiology 165
Environmental factors 167
Pathogenesis 167
Cellular autoimmunity 167
Humoral autoimmunity 169
Insulin autoantibodies 169
Glutamic acid decarboxylase autoantibodies 169
Islet antigen-2 autoantibodies IA-2Ab and IA-2?Ab 170
ZnT8 transporter (SLC30A8) autoantibodies ZnT8Ab 170
Candidate (minor) autoantigens 170
Pancreatic islet pathology before clinical diagnosis 171
Conclusions 171
References 172
11 Other Disorders with Type 1 Phenotype 174
Introduction 174
Atypical diabetes: heterogeneous etiologies of young-onset diabetes 175
Monogenic diabetes 175
Maturity-onset diabetes of the young (MODY) 175
Mitochondrial gene mutations 177
Amylin gene mutations 177
Other genetic mutations affecting pancreatic b-cell function 177
Latent autoimmune diabetes in adults (LADA) 177
Other subtypes of diabetes with type 1 phenotype 178
Conclusion 178
References 178
12 Abnormalities of Insulin Secretion and b-Cell Defects in Type 2 Diabetes 181
Introduction 181
Physiological insulin secretion 181
Natural history of b-cell failure 183
Genetic predisposition 184
Abnormalities of b-cell function precede overt diabetes 185
Insulin secretion progressively worsens after development of T2DM 186
Hyperglycemia 186
Hyperlipidemia 187
Chronic b-cell stimulation 187
Impaired incretin effect 188
Antihyperglycemic treatment 188
b-Cell dysfunction: exhaustion or insufficient mass? 189
Conclusion 191
References 191
13 Insulin Resistance in Type 2 Diabetes 194
Definition and measurement of insulin resistance in humans 194
Insulin resistance as a risk factor for type 2 diabetes mellitus (T2DM) 195
Insulin resistance in skeletal muscle 196
Insulin resistance in the liver 199
Insulin resistance in adipose tissue 200
Stepwise development of tissue-specific insulin resistance 202
Conclusion 204
Acknowledgments 204
References 204
14 Genetic Architecture of Type 2 Diabetes 207
The diabetes epidemic 207
The diabetes spectrum 208
Heritability of T2DM 209
The genetic architecture of T2DM 210
Linkage studies 210
Candidate genes for T2DM 210
Genome-wide association studies (GWAS) identify common variants associated with disease 210
Rare variants with stronger effects are often rare 211
Protective variants 211
Gene–gene and gene–environment interactions 216
Parent-of-origin effects 217
Epigenetics 219
Non-coding RNAs – microRNAs and lincRNAs 220
Difficulties in assigning functions to associated genes 220
Genotype-based treatment 221
Little common genetic basis for T1DM and T2DM 221
A holistic view – systems genetics 222
Conclusions 222
References 222
15 Metabolic Disturbances in Diabetes 225
Introduction 225
Carbohydrate metabolism 225
Carbohydrate metabolism in type 1 diabetes 227
Carbohydrate metabolism in type 2 diabetes 228
Lipid metabolism in type 1 and type 2 diabetes 230
Protein metabolism in type 1 and type 2 diabetes 231
Counter-regulatory hormones 231
Diabetic ketoacidosis 232
References 232
16 Obesity and Diabetes 235
Introduction 235
Definition of obesity and the body fat distribution pattern 235
Obesity is the most potent risk factor for type 2 diabetes 236
Genetic predisposition for obesity and type 2 diabetes 237
Developmental programming of obesity and diabetes 238
Pathophysiology of obesity 238
Environmental factors promoting obesity and type 2 diabetes 239
Pathophysiologic links between obesity and type 2 diabetes 240
Lipids and insulin resistance 240
Lipids and b-cell function 240
Adipose tissue as a secretory organ 241
Signaling pathways of inflammation in adipose tissue 242
Obesity and endoplasmic reticulum stress 243
Obesity and oxidative stress 243
Adipose tissue hypoxia 243
Accumulation of immune cells 243
Role of body fat distribution pattern 243
Treatment of obesity in the context of the metabolic syndrome and type 2 diabetes 244
Management of obesity in people with type 2 diabetes 245
Dietary approaches 245
Antidiabetes drugs and body weight 246
Weight-lowering drugs 246
Bariatric surgery 246
Conclusions 246
References 247
17 The Microbiome and Diabetes 249
The microbiome 249
The intestinal microbiome is associated with body mass 250
Composition of the intestinal microbiome is altered in T2DM 251
The intestinal microbiome can influence intestinal permeability 251
Metabolic endotoxemia 252
Metabolic endotoxemia in T2DM 252
Modulation of the intestinal microbiome is associated with improvements in insulin sensitivity 252
The microbiome contributes to T2DM risk via innate immune pathways 253
The microbiome contributes to T2DM risk via modulation of enteroendocrine cell function 254
The microbiome contributes to T2DM risk via modulation of bile acids 255
Type 1 diabetes 257
Conclusions and perspectives 257
References 257
4 Other Types of Diabetes 261
18 Monogenic Causes of Diabetes 263
Introduction 263
Maturity-onset diabetes of the young 263
Prevalence of MODY mutations 265
Strategies to improve case-finding 266
Use of diagnostic and predictive molecular testing in monogenic diabetes 267
Glucokinase MODY 267
Clinical features 267
Differentiating from type 1 and 2 diabetes 268
Management 268
Glucokinase MODY and pregnancy 268
HNF1A and HNF4A (transcription factor MODY) 269
Clinical features 269
Differentiating from type 1 diabetes 269
Differentiating from type 2 diabetes 270
Management 270
Management in pregnancy 270
Other transcription factor MODY 270
Neonatal diabetes and diabetes diagnosed within 6 months of life 270
Permanent neonatal diabetes 271
Transient neonatal diabetes 272
Diabetes with extrapancreatic features 273
Maternally inherited diabetes and deafness 273
Renal cysts and diabetes (HNF1B MODY) 274
Other monogenic b-cell diabetes with extrapancreatic features 275
Insulin resistance 275
Insulin receptor gene mutations 276
Clinical features 276
Differentiating from type 1 and 2 diabetes 277
Management 277
Inherited lipodystrophies 277
Familial partial lipodystrophy 277
Congenital generalized lipodystrophy (Berardinelli–Seip syndrome) 278
Other inherited forms of lipodystrophy 278
Management of lipodystrophy 278
Other monogenic conditions associated with insulin resistance 278
Conclusions 278
References 278
19 Drug-Induced Diabetes 282
Introduction 282
Glucocorticoids 283
Second-generation antipsychotics 284
Oral contraceptive agents 284
Menopause hormone therapy 285
Thiazide diuretics 285
Beta-adrenoceptor antagonists 286
HMG CoA reductase inhibitors 286
Anti-retroviral therapy for human immunodeficiency virus (HIV) 287
Pentamidine 287
Fluoroquinolones 288
Calcineurin inhibitors 288
Diazoxide 288
Prevention and treatment strategies 289
References 289
20 Endocrine Disorders that Cause Diabetes 292
Introduction 292
Acromegaly 292
Etiology, incidence, and clinical features of acromegaly 292
Disturbance to glucose tolerance in acromegaly 292
Diagnosis and treatment of acromegaly 294
Outcome of acromegaly and the disturbance to glucose tolerance 295
Effects of diabetes on GH–IGF-I axis 296
Cushing syndrome 298
Etiology, incidence, and clinical features of Cushing syndrome 298
Disturbance to glucose tolerance in Cushing syndrome 298
Diagnosis and treatment of Cushing syndrome 299
Outcome of Cushing syndrome and the disturbance to glucose tolerance 301
Effects of diabetes on hypothalamic–anterior pituitary–adrenal cortex axis 301
The role of 11bHSD1 in diabetes 301
Pheochromocytoma and paraganglioma 301
Etiology, incidence, and clinical features of pheochromocytoma and paragangliomas 301
Disturbance to glucose tolerance in pheochromocytomas and paragangliomas 302
Diagnosis and treatment of pheochromocytomas and paragangliomas 303
Outcome of pheochromocytomas and paragangliomas and the disturbance to glucose tolerance 304
Effects of diabetes on adrenal medulla function 304
Other endocrine conditions causing disturbance of glucose tolerance 304
Glucagonoma 304
Somatostatinoma 304
Vasoactive intestinal peptide-producing tumor (VIPoma) 305
Hyperthyroidism 305
Hypothyroidism 306
Primary hyperaldosteronism 306
Primary hyperparathyroidism 306
Hypopituitarism with growth hormone deficiency 306
Endocrine disorders that associate with diabetes 307
Polycystic ovarian syndrome 307
References 307
21 Pancreatic Diseases and Diabetes 311
Introduction 311
Acute pancreatitis 311
Chronic pancreatitis 312
Epidemiology 313
Pathologic features 313
Clinical features and diagnosis 313
Investigations 314
Diabetes in chronic pancreatitis 314
Tropical chronic pancreatitis 316
Hereditary hemochromatosis 317
Etiology and pathology 317
Clinical features 317
Diabetes in primary hemochromatosis 318
Investigations and diagnosis 318
Treatment 319
Secondary hemochromatosis 319
Pancreatic neoplasia 319
Pancreatic surgery and diabetes 319
Management of diabetes caused by pancreatic surgery 319
Cystic fibrosis 320
Diabetes in cystic fibrosis 320
Management 320
Conclusions 320
Acknowledgments 320
References 320
5 Managing the Patient with Diabetes 323
22 Clinical Presentations of Diabetes 325
Introduction 325
Clinical considerations at presentation 325
Types of diabetes 326
Thirst, polydipsia, and polyuria 326
Weight loss 328
Blurred vision 328
Infections 328
Diabetic ketoacidosis 328
Hyperosmolar hyperglycemic syndrome 329
Macrovascular presentations 329
Acute myocardial infarction 329
Acute stroke 330
Microvascular presentations 330
Eye presentations 330
Neuropathic syndromes 331
Pregnancy 331
Screening 332
Other presentations 333
Conclusions 333
References 333
23 The Aims of Diabetes Care 334
Introduction 334
St. Vincents Declaration 335
The diabetes care team 335
Improving the outcome of the consultation 336
Following diagnosis 338
Issues relating to diagnosis 338
Diabetes education 338
Ongoing clinic visits 339
Glycemic management 339
Assessment of cardiovascular risk 341
Microvascular complications 341
Diabetes emergencies 342
Lifestyle issues 343
Psychological issues 343
Sexual health 343
Inpatient diabetes care 344
Involving people with diabetes in the planning of healthcare and service development 344
Conclusion 344
Acknowledgments 344
References 344
24 Educating the Person with Diabetes 346
Introduction 346
Theory underlying diabetes education 347
Identification and use of theory to guide method 349
Health education methods 349
Modalities of education 349
Educator skills in group-based diabetes education 350
Dialogue and participation in diabetes education—practical examples 351
Psychosocial support in diabetes education 352
Family perspectives in diabetes education 356
Evaluation of diabetes education 356
Conclusion 358
References 358
25 Lifestyle Issues: Diet 361
Introduction 361
Energy balance and body weight 361
Carbohydrate and diabetes 364
Quantity 364
Carbohydrate quality 365
Dietary fiber 365
Dietary mono- and disaccharides 365
Dietary fat 366
Saturated fat 366
Polyunsaturated fat 366
Monounsaturated fat 367
Trans fats 367
Dietary cholesterol 367
Protein 367
Micronutrients 368
Salt or sodium 368
Sterols and stanols 368
Alcohol 368
Diet in special circumstances 368
Diet in pregnancy 368
Diet in children with diabetes 369
Exercise and insulin-treated diabetes 369
References 369
26 Lifestyle Issues: Exercise 373
Defining exercise, type of exercise and intensity 373
Type 1 diabetes and exercise 374
Prevention of type 1 diabetes 374
Treatment of type 1 diabetes 374
Exercise and type 2 diabetes 380
Prevention of type 2 diabetes 380
Treatment of type 2 diabetes 382
Gestational diabetes and exercise 386
Prevention of gestational diabetes 386
Treatment of gestational diabetes 386
Exercise advice in type 1 and type 2 diabetes 387
Exercise guidelines 387
Minimizing risk of exercise-related adverse events 387
Specific considerations for people with type 1 diabetes who exercise 387
Specific considerations for people with type 2 diabetes 390
References 390
27 Monitoring Diabetes 394
Why monitor? 394
Tests and their characteristics 395
Measurement of glycated hemoglobin 395
Measurement of fructosamine 397
Measurement of blood glucose 397
Measurement of urinary glucose 399
Monitoring in clinical practice 399
Monitoring in type 1 diabetes 399
Monitoring in type 2 diabetes 400
Gestational diabetes mellitus 402
Monitoring of diabetes in special situations 402
The future of monitoring in diabetes 403
Conclusions 403
References 403
28 Drug Therapy: Special Considerations in Diabetes 405
Introduction 405
Drugs that raise blood glucose concentrations 405
Drugs that lower blood glucose concentration 406
Sulfonylureas 406
Other antidiabetes agents 407
Other drugs 408
Drug interactions that affect blood glucose concentrations 410
Drugs that interact to enhance the actions of insulin secretagogues 410
Interactions with metformin 410
Interactions with other antidiabetes agents 410
Hazards of general drugs when used in people with diabetes 411
Drugs with cardiovascular actions 411
Special precautions in diabetic complications 415
Drug interference with monitoring of diabetic control 415
Conclusions 415
References 415
6 Treatment of Diabetes 419
29 Insulin and Insulin Treatment 421
Life (and death) before insulin 421
The discovery of insulin 421
The first insulins 422
Modifying the duration of action of insulin without altering its molecular structure 423
Modifying the duration of insulin action through altering its molecular structure 424
Biosimilar insulins 425
Different insulin concentrations 425
Reproducing physiological insulin delivery—the size of the problem 425
Oral, inhaled, intraperitoneal and intramuscular routes of insulin administration 426
Technique for subcutaneous injection of insulin 426
Complications of subcutaneous insulin therapy 428
Insulin regimens 428
Basal only regimen 428
Combinations of prandial and basal insulins 429
Insulin mixtures 430
Selecting the most appropriate insulin regimen 430
Type 1 diabetes 430
Type 2 diabetes 431
Starting insulin for the first time 431
Use of animal, human, and analog insulins 432
Assessments of glycemic control 432
Declaration of interest 432
References 432
30 New Technologies for Glucose Monitoring and Insulin Administration 434
Introduction 434
Episodic blood glucose monitoring 434
Real-time continuous glucose monitoring 436
Clinical efficacy of RT-CGM 437
Practical issues with the use of RT-CGM 438
Continuous subcutaneous insulin infusion pumps 440
Glycemic control with insulin pumps compared with multiple daily insulin injections 440
Quality of life benefits and patient expectations 442
Bolus calculators and insulin-on-board 442
Patch pumps 443
Closed-loop insulin delivery: the artificial pancreas 443
Insulin pens 444
Inhaled insulin 444
References 444
31 Oral Glucose-Lowering Agents 446
Introduction 447
Pathophysiological considerations 447
Guidelines and algorithms 448
Biguanides 452
Mode of action 452
Pharmacokinetics 452
Indications and contraindications 453
Efficacy 454
Adverse effects 454
Sulfonylureas 455
Mode of action 455
Pharmacokinetics 457
Indications and contraindications 457
Efficacy 458
Adverse effects 458
Meglitinides (short-acting prandial insulin releasers) 459
Mode of action 459
Pharmacokinetics 459
Indications and contraindications 459
Efficacy 460
Adverse effects 460
Thiazolidinediones 460
Mode of action 460
Pharmacokinetics 461
Indications and contraindications 462
Efficacy 462
Adverse effects 462
DPP-4 inhibitors 463
Mode of action 463
Pharmacokinetics 464
Indications and contraindications 465
Efficacy 465
Adverse effects 465
SGLT-2 inhibitors 466
Mode of action 466
Pharmacokinetics 466
Indications and contraindications 466
Efficacy 467
Adverse effects 468
??????-Glucosidase inhibitors 468
Mode of action 468
Pharmacokinetics 468
Indications and contraindications 469
Efficacy 470
Adverse effects 470
Bromocriptine 470
Mode of action 470
Pharmacokinetics 470
Indications and contraindications 470
Efficacy 471
Adverse effects 471
Colesevelam 471
Mode of action 471
Pharmacokinetics 471
Indications and contraindications 471
Efficacy 471
Adverse effects 471
Antiobesity therapies 471
Fixed-dose combinations 471
Conclusions 472
References 473
32 Non-Insulin Parenteral Therapies 475
Introduction 475
Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) 475
Introduction 475
Historical overview 476
GLP-1 physiology and antidiabetes actions 477
GLP-1 receptor agonists for the treatment of diabetes 479
Conclusion 485
Amylin and amylin analogs 486
Introduction and historical overview 486
Amylin physiology 486
Amylin analogs 487
Future perspectives: amylin incorporated in dual agonist? 488
References 488
33 How to Use Type 2 Diabetes Treatments in Clinical Practice: Combination Therapies 491
Introduction 491
Pathophysiological rationale for using multiple therapies 492
Individual glucose-lowering drug classes 493
Major classes 493
Minor classes 503
Combination therapy: uses and evidence 505
The evidence basis 506
Combination therapy: specific strategies 506
Dual combination therapy 506
Triple combination therapy 508
Combinations with insulin 508
Is combination therapy synergistic? 508
Early versus sequential combination therapy 508
Fixed-dose combinations 509
Guidelines 509
Future research needs 509
Conclusions 510
References 510
34 In-Hospital Treatment and Surgery in People with Diabetes 513
Introduction 513
Known diabetes in hospital 513
Undiagnosed diabetes and stress hyperglycemia in hospital 513
Pathophysiology of hyperglycemia in acute illness 513
Evidence of harm from in-hospital hyperglycemia and effect of glucose lowering 514
Glycemic targets for hospitalized inpatients 515
The intensive care unit (ICU) 515
General ward patients 515
Surgical patients 515
Current recommended standards of care for hospital inpatients with diabetes 516
Minimizing length of stay 517
Patient safety 517
Diabetes self-management 517
Patient satisfaction 517
The role of the diabetes specialist team 518
Staff education 518
Management of in-hospital hyperglycemia 519
Medication to manage in-hospital hyperglycemia 519
Self-management of diabetes in hospital 519
Technology 520
Subcutaneous and intravenous insulin protocols 520
Indications for an intravenous insulin infusion 520
Preparation and delivery of an intravenous insulin infusion 521
Transition from intravenous to subcutaneous insulin 521
Avoiding and treating in-hospital hypoglycemia 521
Frequency of hypoglycemia in hospitalized patients 521
Causes of in-hospital hypoglycemia 523
Morbidity and mortality associated with in-hospital hypoglycemia 523
Evidence for treatment options 523
Management of in-hospital hypoglycemia 523
Surgery in people with diabetes 524
Primary care 524
Preoperative assessment 524
Hospital admission 526
While in the operating theater and recovery 527
Postoperative period 527
Hospital discharge 527
Emergency surgery 527
Continuous subcutaneous insulin infusions (CSIIs “pumps”)
Glucocorticoid use 528
Steroid therapy: impact on blood glucose 528
Monitoring 528
Medication options for people taking once-daily steroid therapy 528
Medication options for people taking multiple daily doses of steroid 528
Hospital discharge 529
Steroid treatment in end-of-life care 529
Foot care 529
Conclusions 529
References 530
35 Hypoglycemia in Diabetes 533
Overview of the clinical problem 533
Physiology of glucose counter-regulation 534
Hypoglycemia and the brain 534
Responses to hypoglycemia 534
Clinical manifestations of hypoglycemia 534
Maintenance of systemic glucose balance 535
Pathophysiology of glucose counter-regulation in diabetes 536
Insulin excess 536
Defective glucose counter-regulation and hypoglycemia unawareness 536
Hypoglycemia-associated autonomic failure 537
Risk factors for hypoglycemia in diabetes 540
Absolute or relative insulin excess 540
Compromised defenses against hypoglycemia 541
Magnitude of the clinical problem of hypoglycemia in diabetes 541
Frequency of hypoglycemia 541
Impact of hypoglycemia 542
Clinical definition and classification of hypoglycemia 543
Prevention and treatment of hypoglycemia in diabetes 543
Prevention of hypoglycemia: hypoglycemia risk factor reduction 543
The clinical problem of hypoglycemia in children 546
Definition of hypoglycemia in youth 546
Prevalence and incidence of hypoglycemia in youth 546
Risk factors for hypoglycemia in the pediatric population 546
Physiology of counter-regulation in youth with T1DM 547
Effects and consequences of hypoglycemia in youth 548
Perspective on hypoglycemia in diabetes 549
Acknowledgments 549
Disclosures 549
References 549
36 Acute Metabolic Complications of Diabetes: Diabetic Ketoacidosis and the Hyperosmolar Hyperglycemic State 554
Introduction 554
Diabetic ketoacidosis 554
Definitions 554
Pathogenesis and pathophysiology 555
Precipitating factors 556
Diagnosis and clinical presentation 556
Management 557
Comorbidity 558
Complications 558
Prevention 559
Hyperosmolar hyperglycemic state 559
References 559
7 Microvascular Complications inDiabetes 561
37 Pathogenesis of Microvascular Complications 563
Diabetic angiopathy: definition and clinical features 563
Pathogenesis of microvascular complication: the role of hyperglycemia 564
Differences in cell response to hyperglycemia 564
Glycemic memory or legacy effect 565
Determinants of individual susceptibility to hyperglycemia-induced damage 567
Pathogenesis of microvascular complication: beyond hyperglycemia 567
Metabolic factors 568
Hemodynamic factors 569
Growth factors/cytokines 569
Intracellular factors 570
The innate immune system 571
Conclusion 571
Acknowledgments 572
References 572
38 Diabetic Retinopathy 574
Introduction 574
Nomenclature 574
Pathophysiology 575
Development 575
Early changes with no vision loss 575
Vision-threatening diabetic retinopathy 576
Epidemiology 579
Prevention 579
Screening 580
Diagnosis 581
Treatment 581
Retinal photocoagulation 581
Intravitreal angiostatic treatment 583
Exploration of diabetic retinopathy 584
References 584
39 Diabetic Nephropathy 586
Introduction 586
Definitions 586
Screening for and classification of chronic kidney disease 587
Natural history and histopathology 587
Classical diabetic nephropathy 587
Non-classical diabetic kidney disease 589
Changing epidemiology of kidney disease in diabetes 589
T1DM 589
T2DM 589
Risk factors and markers for chronic kidney disease in diabetes 589
Glucose control 590
Blood pressure 590
Other metabolic factors 590
Hyperfiltration 590
Genetic factors 590
Ethnicity 590
T2DM developing in young people 590
Albuminuria and GFR 590
Other risk factors 591
Association of diabetic kidney disease with cardiovascular disease 591
Microvascular complications 592
Investigation of kidney disease in diabetes 592
Excluding other treatable causes of kidney disease 592
Monitoring kidney disease 593
Prevention and management of diabetic kidney disease 593
Glucose control 593
Blood pressure control 594
Low-protein diet 595
Lipids 595
Cardiovascular risk—other factors 595
Weight loss 595
Further management of chronic kidney disease stage 3 or poorer 595
Monitoring anemia and bone chemistry 595
Monitoring glucose control 595
Glucose-lowering agents (Table 39.4) 595
Anemia 596
When to refer to nephrology 596
Organization of care 596
Pregnancy in women with diabetes and chronic kidney disease 596
References 596
40 Diabetic Peripheral and Autonomic Neuropathy 600
Diabetic peripheral neuropathy 600
Classification, epidemiology, and clinical impact 600
Clinical manifestations 601
Pathogenetic mechanisms 605
Diagnostic assessment 605
Treatment 610
Diabetic autonomic neuropathy 615
Clinical impact 615
Cardiovascular autonomic neuropathy 616
Silent ischemia 616
Diagnostic assessment 618
Management 618
Gustatory sweating 620
Gastrointestinal dysfunction 620
Esophageal dysfunction 620
Gallbladder dysfunction 620
Diabetic gastroparesis 620
Diabetic diarrhea 622
Colonic dysfunction 623
Anorectal dysfunction 623
Autonomic neuropathy of the urogenital system 624
Urinary bladder dysfunction 624
Erectile dysfunction 625
Other sexual problems in men 626
Female sexual dysfunction 626
References 626
8 Macrovascular Complications in Diabetes 629
41 Pathogenesis of Macrovascular Complications in Diabetes 631
Epidemiology of diabetic macrovascular complications 631
Pathogenesis of diabetic macrovascular disease 632
Role of hyperglycemia 632
Clinical trials and hyperglycemia 632
Direct and indirect glycotoxicity 633
Insulin resistance 634
Formation of AGE 634
Direct effects of vascular AGE accumulation 635
Interaction with the renin–angiotensin system 637
Role of vasoactive hormones in diabetes-related atherosclerosis 637
Classic RAS 637
Novel aspects of the RAS: ACE2 637
AT receptors 637
Role of the RAS in macrovascular disease 637
RAS activation and endothelial dysfunction 638
RAS and regenerative endothelial cell repair 639
Role of AT-(1–7) and ACE2 in endothelial dysfunction 639
RAS activation and atherosclerosis 639
ACE2 and diabetes accelerated atherosclerosis 639
RAS and oxidative stress 640
Therapeutic implications 640
The endothelin system 641
Role of ET in diabetic macrovascular complications 641
Urotensin II 641
Role of urotensin II in atherosclerosis 642
Oxidative stress 642
Role of reactive oxygen species in diabetes-accelerated atherosclerosis 642
NADPH oxidase production of ROS 642
Inflammation and immune responses 642
TNF-related apoptosis-inducing ligand and osteoprotegerin 643
Complement activation 643
Interventions to reduce diabetes-associated macrovascular complications 644
Glucose control 644
Hypertension 644
Choice of antihypertensive treatment 644
Renal denervation 645
Dyslipidemia 645
Hypercoagulability 645
Novel therapies 645
Multifactorial approaches 645
References 645
42 Cardiovascular Risk Factors: Hypertension 649
Introduction 649
Size of the problem 649
Causes of hypertension in diabetes 650
Hypertension in the metabolic syndrome 650
Hypertension and diabetic nephropathy 651
Impact of hypertension in diabetes 652
Screening for hypertension in diabetes 653
Measurement of blood pressure 653
Diagnosis of hypertension in diabetes 653
Investigation of hypertension in diabetes 653
Management of hypertension in diabetes 655
Non-pharmacological treatment 655
Antihypertensive drug therapy 655
Treatment strategies 657
Special considerations in ethnic groups 658
Outcome of treating hypertension in diabetes 658
Conclusions 659
References 661
43 Diabetic Dyslipidemia and Risk of Cardiovascular Disease 663
Introduction 663
CVD risk factors in diabetes 664
Glucose 664
Dyslipidemia 665
LDL cholesterol 665
Statins 665
Other LDL-C-reducing drugs 666
Non-HDL-C and ApoB 666
LDL subfractions 666
Triglycerides 667
Statins and triglycerides 667
Fibrates 667
Omega-3 fatty acids 667
Other triglyceride-reducing agents 668
HDL-C 668
HDL infusion studies 668
Niacin 668
CETP inhibition 669
Guidelines and lipids in diabetes 670
Future drug developments and drug targets 670
Conclusions 670
References 670
44 Ischemic Heart Disease in Diabetes 673
Epidemiology 673
Pathophysiological perspective 674
How can cardiovascular risk be reduced in persons with diabetes? 674
Glucose lowering 674
Lipid management 676
Blood pressure management 677
Aspirin treatment 677
Screening for coronary heart disease in diabetes 678
References 678
45 Congestive Heart Failure 679
Introduction 679
Symptoms and diagnosis 680
The diagnosis and definition of heart failure 680
The diagnosis and definition of glucose abnormalities 680
Epidemiology 681
Risk factors for heart failure and diabetes 681
Prevalence of heart failure and glucose abnormalities 681
Incidence of heart failure and glucose abnormalities 682
Pathophysiology 683
Heart failure 684
Heart failure and diabetes 684
Prognosis 685
Heart failure in general 685
Diabetes and heart failure 686
Treatment 686
General aspects 686
Pharmacological therapy of heart failure 687
Glucose-lowering treatment 688
HF-PEF 689
Metabolic modulators 689
Importance of revascularization 689
Gender aspects 689
References 690
46 Cerebrovascular Disease 693
Epidemiology of stroke in general 693
Diabetes as a risk factor for stroke 693
Stroke in people with diabetes 694
Prediabetes and other risk factors 694
Pathophysiology of ischemic stroke in diabetes 696
Primary prevention of stroke in persons with diabetes 697
Treatment of acute stroke in persons with diabetes 698
Secondary Prevention of Stroke in Diabetes 700
Conclusions 701
References 701
47 Peripheral Vascular Disease 703
Introduction 703
Peripheral arterial disease 703
Incidence 704
Pathophysiology 704
Diagnosis 705
Prognosis 705
Treatment 705
Acute lower limb ischemia 709
Atherosclerosis of renal and mesenteric arteries 710
Ischemia of the arm 710
Aortic aneurysmal disease (abdominal aortic aneurysm) 711
Peripheral aneurysms 713
Carotid artery disease 714
Pathophysiology and symptoms 714
Prognosis 714
Diagnosis 714
Treatment 714
Carotid stenting 716
References 716
9 Other Complications of Diabetes 719
48 Foot Problems in People with Diabetes 721
Introduction 721
Epidemiology and economic aspects of diabetic foot disease 722
Health economics of diabetic foot disease 723
Etiopathogenesis of diabetic foot lesions 723
Peripheral vascular disease 723
Diabetic neuropathy 723
Other risk factors 724
Pathway to ulceration 725
Prevention of diabetic foot ulcers 725
Screening 725
Intervention for high-risk individuals 726
Foot ulcers: diagnosis and management 727
Foot ulcer classification 727
Wound healing in the diabetic foot 728
Offloading 729
Dressings 730
Management of infection 730
Adjunctive therapies 732
Charcot neuroarthropathy 732
Conclusions 733
The team approach 733
References 733
49 Sexual Function in Men and Women with Diabetes 736
Male erectile dysfunction 736
Physiology of erectile function 736
Clinical aspects of erectile dysfunction in diabetes 739
Erectile dysfunction as a risk factor for cardiovascular disease 739
Smoking and alcohol consumption 739
Quality of life issues 739
Assessment and investigation of erectile dysfunction indiabetes 740
General advice 740
Treatment options 741
Organization of the management of erectile dysfunction 744
Conclusions on male sexual dysfunction 745
Female sexual dysfunction 745
Management of female sexual dysfunction 745
Genitourinary infections in women with diabetes 746
Conclusions on female sexual dysfunction 746
Contraception 746
Contraindications to pregnancy 746
Method of contraception 746
Summary 747
Hormone replacement therapy 747
HRT and glucose tolerance 747
HRT and lipids 747
HRT and blood pressure 748
HRT and ischemic heart disease 748
HRT and osteoporosis 748
Summary 748
References 748
50 Gastrointestinal Manifestations of Diabetes 751
Introduction 751
Epidemiology 751
Pathophysiology 752
Normal gastrointestinal motor functions 752
Pathophysiology of diabetic enteropathy: insights from animal studies 753
Pathophysiology of diabetic enteropathy in humans 754
Gastric dysfunctions 754
Diabetic diarrhea 755
Fecal incontinence 756
Constipation 756
Clinical manifestations 756
Dysphagia and heartburn 756
Dyspepsia and gastroparesis 756
Diarrhea and constipation 757
Abdominal pain 757
Diagnostic tests 758
Management 761
Gastroparesis and dyspepsia 761
Diabetic diarrhea 762
Constipation 762
Acknowledgment 762
References 762
51 Diabetes and Non-Alcoholic Fatty Liver Disease 765
Introduction 765
Definition and epidemiology 765
NAFLD and the metabolic syndrome 766
NAFLD and diabetes 766
Type 2 diabetes 766
Type 1 diabetes 767
Histologic subtypes 767
Why does NASH occur? 767
Clinical features 769
Extrahepatic-associations of NAFLD 769
Natural history of NAFLD 769
Hepatocellular carcinoma 770
Diagnosis and assessment 770
Liver enzymes 770
Imaging 771
Liver biopsy: indications and limitations 771
Non-invasive methods of assessing NAFLD 772
Current practice 772
Management 773
Diet and exercise 773
Lifestyle intervention trials in people with NAFLD and T2DM 773
Vitamin E 774
Thiazolidinediones (“glitazones”) 774
Metformin 774
Incretins 774
Obeticholic acid (6-ethylchenodeoxycholic acid, OCA) 774
Probiotics 775
Statins and hyperlipidemia 775
Bariatric surgery 776
Managing people with cirrhosis 776
Hepatocellular carcinoma surveillance 776
Liver transplantation 776
Pediatric NAFLD 776
References 776
52 The Skin in Diabetes 779
Introduction 779
Metabolic manifestations 779
Acanthosis nigricans 779
Achrochordons (skin tags) 781
Necrobiosis lipoidica diabeticorum 781
Diabetic bullae (bullosis diabeticorum) 783
Diabetic thick skin 783
Scleredema of diabetes 783
Yellow skin and nails 784
Eruptive xanthomas 784
Vascular changes 784
Diabetic dermopathy (shin spots) 784
Rubeosis faciei 785
Periungual telangiectasia 785
Lower limb vascular changes 785
Perforating dermatoses 785
Calcific uremic arteriolopathy (calciphylaxis) 785
Infections 786
Bacterial infections 786
Fungal/yeast infections 786
Associated conditions 787
Vitiligo 787
Lichen planus 788
Pruritus 788
Clear-cell syringomas 788
Glucagonoma 788
Disseminated granuloma annulare 788
Iatrogenic 789
Reactions to insulin 789
Reaction to oral antidiabetes agents 790
References 790
53 Bone and Rheumatic Disorders in Diabetes 793
Musculoskeletal disease in diabetes 793
Background 793
Fibroproliferative disorders of soft tissue 793
Disorders of joints 796
Skeletal disease in diabetes 799
References 804
54 Diabetes and Cancer: Evidence for Risk, Methodology and Implications 809
Background 809
Diabetes and cancer risk: the epidemiological evidence 810
Cancer incidence 810
Cancer-related mortality 810
Type 1 diabetes and cancer 811
Interpretation of the epidemiological evidence 811
Diabetes and cancer: potential confounding 811
Diabetes and cancer: potential biases 812
Hyperglycemia versus hpyerinsulinemia hypotheses 813
Pharmaco-epidemiology: glucose-lowering agents and cancer risk 814
Interpretation 814
Metformin and cancer risk 814
Insulins and cancer risk 815
Pioglitazone and cancer risk 815
Incretin-based drugs and cancer risk 816
Other medications 816
Impact of diabetes on outcome after cancer diagnosis 816
Clinical implications 816
Acknowledgments 817
Conflict of interest 817
References 817
55 Diabetes and Infections 819
Introduction 819
Diabetes, the immune system and host factors 820
Host immune response 820
Other host-related factors 821
Diabetic complications 822
Organism-specific factors 822
Bidirectionality: the effect of infections on diabetes 823
HIV/AIDS 824
Specific infections either strongly associated with diabetes or in which the presence of diabetes is important 825
Infections involving the head and neck 825
Respiratory tract infections and tuberculosis 827
Diabetes and tuberculosis 827
Infections of the urinary tract 828
Epidemiology and risk factors 828
Intra-abdominal infections other than those within the urinary tract 831
Emphysematous cholecystitis 831
Liver and other intra-abdominal abscesses 831
Skin and superficial soft tissue infections 832
Skin and subcutaneous tissues 832
Deeper soft tissue infections 833
Infected diabetic foot 834
Bone and joint infections 834
Iatrogenic and surgical site infections 834
Principles of treatment, prevention, and general care 835
General principles 835
Glycemic control 835
References 836
10 Psychosocial Aspects of Diabetes 839
56 Psychological Factors and Diabetes Mellitus 841
Introduction 842
Psychological risk factors for the development of diabetes 842
The psychological impact of diabetes and its complications 843
Psychological distress shortly after diagnosis 843
Psychological reactions emerging in the course of diabetes 843
Psychological reactions to acute biomedical complications 845
Psychological reactions to long-term biomedical complications 845
Quality of life 846
The impact of psychological factors on diabetes management 847
Psychological traits and glycemia 848
Psychological states and glycemia 848
Family characteristics, interactions, and glycemia 849
The impact of behavioral factors (“adherence”) on diabetes management 849
Behavioral factors: the example of self-monitoring of blood glucose (SMBG) 850
Methodological issues in self-care assessment 850
Interventions to reduce psychological distress and improve quality of life, self-care, and glycemic control 850
Reducing depression and diabetes distress 850
Empowerment-based approaches to improve outcomes 851
Structured training/education to improve outcomes 851
Technological approaches to improve outcomes 852
Cognitive-behavioral approaches to improve outcomes 852
Neuropsychological and cognitive consequences of diabetes 853
CNS sequelae of diabetes in children and adolescents 853
Brain structure and function in adults with type 1 diabetes 855
Hyperglycemia and neurocognitive dysfunction in people with diabetes 856
Conclusions 856
Acknowledgments 856
References 856
57 Psychiatric Disorders and Diabetes 860
Introduction 860
Mood disorders 861
Case definition 861
Epidemiology 861
Who is likely to develop depression? 862
Depressive disorders as a risk factor for diabetes 862
Proposed mechanisms linking depression and diabetes 863
Consequences of depression in diabetes 864
Management of people with diabetes and depression 864
Psychotic disorders 866
Case definitions 866
Epidemiology 867
Diabetes and severe mental illness 867
Eating disorders 872
Case definitions 872
Clinical features 873
Epidemiology 874
Etiology 874
Impact on diabetes outcomes 875
Management of eating disorders 875
Acknowledgments 876
References 876
58 Social Aspects of Diabetes 879
Introduction 880
Driving 880
Hypoglycemia 881
Visual impairment 882
Statutory requirements for drivers with diabetes 882
Employment 884
Unemployment, sickness and diabetes 885
Prison and custody 885
Insurance 886
Alcohol 886
Alcohol consumption and risk of diabetes 886
Alcohol and glycemic control 887
Alcohol and diabetic complications 887
Recommended alcohol intake 888
Recreational drugs 888
Regulation 888
Prevalence of recreational drug use 889
Impact of recreational drug use on diabetes 889
Advice on recreational drug use in diabetes 890
Travel 890
Preparation for travel 891
Long flights and crossing time zones 892
Insulin treatment in hot climates 893
Food and drink 894
Intercurrent illness 894
Recreational activities 894
Leaving home 894
Students with diabetes 894
References 895
11 Diabetes in Special Groups 897
59 Diabetes in Childhood 899
Spectrum of diabetes in children 899
Manifestation, diagnosis, and initial treatment 900
Clinical presentation and diagnosis 900
Diabetic ketoacidosis 901
Pediatric ambulatory diabetes care 903
Initial education 903
Continuing education 903
Diabetes management in school 904
Insulin treatment 904
Subcutaneous insulin injection regimens 905
Insulin pump therapy 905
Nutrition 906
Age-specific advice 907
Exercise 907
Preventing hypoglycemia 907
Insulin adjustments 907
Delayed hypoglycemia 907
Ketones and exercise 908
Hypoglycemia 908
Signs and symptoms 908
Treatment 908
Hypoglycemia unawareness 908
Prevention 908
Sick-day management 909
Monitoring and goals of diabetes management 910
Continuous glucose monitoring 911
Psychological care 911
Screening and early treatment of risk factors for complications and associated conditions 912
Dyslipidemia 912
Microalbuminuria 913
Elevated blood pressure 913
Retinopathy 913
Celiac disease 913
Thyroid disease 914
Addison disease 914
References 914
60 Adolescence and Emerging Adulthood: Diabetes in Transition 916
Introduction 916
Demographic information about diabetes 917
Physical changes during adolescence 917
Developmental stages 917
Adolescence (ages 13–18 years) 917
Emerging adulthood 921
Changes in family involvement 921
Diabetes technologies 922
Type 2 diabetes in adolescence and transition 922
Acute and chronic complications in young adults diagnosed with diabetes in childhood 924
What is transition? 924
Problems with transition 924
Existing transition programs and interventions 926
Summary 927
References 927
61 Diabetes in Pregnancy 929
Introduction 930
Changes in glucose metabolism in pregnancy 930
Classification of diabetes in pregnancy 931
New-onset T1DM in pregnancy 931
Fulminant-onset T1DM 932
New-onset T2DM in pregnancy 932
Cystic fibrosis-related diabetes and pregnancy 932
Monogenic diabetes 932
Effects of diabetes on pregnancy 932
Fertility and conception 932
Miscarriage 933
Congenital anomalies 933
Fetal morbidity 933
Other neonatal complications 937
Effects of maternal diabetic ketoacidosis and hypoglycemia on the fetus 937
Effects of pregnancy on diabetes complications 938
Hypertensive disorders of pregnancy 940
Management of diabetes in pregnancy 942
Prepregnancy counseling 942
Management of T1DM in pregnancy 943
Management of T2DM in pregnancy 945
Obstetric monitoring 945
Labor and delivery 946
Management of glycemia during labor 946
General management 947
Fetal overnutrition: gestational diabetes, obesity, and gestational weight gain 947
Gestational diabetes 947
Background 947
RCTs of treatment of mild GDM 948
The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study 949
The International Association of Diabetes Pregnancy Study Groups (IADPSG) recommendations 949
GDM: disease or risk factor? 951
Management of GDM 951
Oral antidiabetes agents in GDM 952
Delivery 952
Postpartum reclassification of diabetes 952
Long-term effects of GDM 952
References 953
62 Diabetes in Old Age 959
Introduction 959
Epidemiology 959
Pathogenesis 960
Increased insulin resistance 960
Decreased insulin secretion 960
Diabetes phenotype in old age 960
Comorbidity burden 961
Geriatric syndromes 961
Frailty 961
Clinical presentation 961
Diagnosis 962
Management 962
Lifestyle modifications 962
Hyperglycemia 963
Hypertension 963
Dyslipidemia 965
Aspirin therapy 965
Multiple risk intervention 965
Reverse metabolism 965
Special considerations in old age 965
Hypoglycemia 965
Dementia 967
Hypoglycemia–dementia interaction 967
Management of Diabetes 968
Glycemic targets 968
Polypharmacy 969
Care homes 969
Conclusion 970
Future perspectives 970
References 971
63 Diabetes at the End of Life 973
Dying with diabetes 973
End of life 974
The management of diabetes at the end of life 975
Glycemic targets 975
Medicines management during the last year of life 976
Other medication 976
Insulin 976
Continuous subcutaneous infusion of insulin—insulin pumps 976
Nutrition 978
Management of diabetes in those treated with glucocorticosteroids 978
Withdrawal of diabetes and other medication 978
Workforce 979
References 979
12 Delivery and Organization of Diabetes Care 981
64 The Role of the Multidisciplinary Team Across Primary and Secondary Care 983
Background 983
Upskilling of primary or community care professionals in multidisciplinary teams 984
Support of multidisciplinary teams in structured patient education in diabetes 984
Multidisciplinary teams in diabetes care models 985
Enhancement of multidisciplinary teams through the use of information technology 985
Multidisciplinary teams in the management of complexities in CVD risk prevention 985
Multidisciplinary teams in renal disease in diabetes 986
Multidisciplinary teams in the care of people with diabetic retinopathy 987
Multidisciplinary teams in the care of people with diabetic foot problems 987
Multidisciplinary teams in the care of women with diabetes in pregnancy 988
Multidisciplinary teams in the care of young people with T2DM 988
Multidisciplinary teams in the care of elderly people with diabetes 988
The staff composition of a multidisciplinary diabetes team 989
Community pharmacists 989
Practice nurses 989
General or family practitioners 989
Diabetes specialists 990
Dieticians 990
Community health workers 990
Conclusion 990
References 991
65 Models of Diabetes Care Across Different Resource Settings 993
Introduction 993
A comprehensive approach 996
Integrated healthcare 996
Continuity, access, coordination, and teamwork 997
Continuity of care 997
Access to all 998
Coordination of care 999
Teamwork 999
Patient-centered care 999
A family and community orientation 1000
Clinical governance 1000
Information technology 1001
Electronic health records 1001
Registries 1001
Telemedicine and remote monitoring 1001
Clinical decision support tools 1002
Provider training and education 1002
Supporting self-management and behavior change 1002
Digital glucose monitoring 1002
Online health information, support groups, and social media 1003
Conclusion 1003
References 1003
13 Future Directions 1005
66 Future Drug Treatments for Type 1 Diabetes 1007
Introduction 1007
New biosynthetic human insulin analogs 1008
Ultralong-acting insulins 1008
Ultrafast-acting insulins 1010
Alternative means of accelerating insulin absorption and action 1011
Insulin infusion and injection site-warming devices 1011
Administration via intradermal microneedles 1011
Pretreatment of new infusion sites with hyaluronidase 1011
New generation of insulins in development 1011
Smart insulins 1011
Adjunctive therapies 1011
Metformin 1012
GLP-1 receptor agonists 1012
DPP-4 inhibitors 1012
SGLT inhibitors 1012
Artificial pancreas development 1013
Limitations of sensor-augmented pump therapy 1013
Low-glucose (threshold) suspend 1014
Predictive low-glucose suspend 1014
Closed-loop algorithm considerations 1014
Early-phase/inpatient closed-loop studies 1014
Outpatient studies 1015
Improved glucagon preparations 1015
Stable liquid preparations 1016
Dry powder intranasal preparations 1016
Conclusion 1016
References 1016
67 Future Drug Treatments for Type 2 Diabetes 1020
Introduction 1020
Development of new antidiabetes agents 1020
Modifiers of carbohydrate digestion and absorption 1021
Supporting pancreatic b-cell function 1021
Glucokinase activators 1022
Fatty acid receptor agonists 1022
Imeglimin 1023
Incretins 1023
Bile acid receptor agonists 1025
Inhibitors of glucagon secretion and action 1025
Insulin mimetic agents 1025
Insulin potentiating agents 1025
Adipokines 1027
Fibroblast growth factors 1027
Peroxisome proliferator-activated receptor ?????? agonists 1027
Vitamins and minerals 1027
Hydroxysteroid dehydrogenase 1 inhibitors 1028
Sodium–glucose co-transporter inhibitors 1028
Suppression of glucose production 1028
Direct enhancers of glucose metabolism 1029
Antiobesity agents 1029
Sirtuins 1030
Pharmacogenomics 1030
Safety 1030
Conclusion 1030
References 1030
68 Stem Cell Therapy in Diabetes 1032
Why use stem cells in individuals with diabetes? 1032
What is a stem cell? 1032
Stem cells for insulin replacement 1033
Healing the heart 1033
Creating new vessels 1035
Conclusions 1036
References 1036
69 Islet Transplantation 1037
Introduction 1037
Background history 1038
Early human studies 1038
Pancreas transplantation 1039
Islet transplantation and the Edmonton Protocol in the year 2000 1039
Islet isolation 1039
Immunosuppression 1039
Islet transplantation current state-of-the-art 1040
Islet preparation 1040
Transplant procedure 1040
Immunosuppression 1041
Islet transplantation outcomes 1041
Glycemic control 1041
Diabetes complications 1042
Procedure-related complications 1043
Side effects of immunosuppression 1043
Immune sensitization 1044
Indications and contraindications for islet transplantation 1044
Patient evaluation 1044
Challenges and future directions 1045
Islet shortage 1045
Islet engraftment 1045
Monitoring the islet graft 1045
Promoting graft survival 1045
Immunosuppression toxicity 1046
Summary and conclusions 1046
References 1046
70 Gene Therapy for Diabetes 1049
Introduction to gene therapy 1049
Viral vectors 1050
Gene therapy for diabetes 1050
Gene therapy for T1DM 1050
Gene therapy for T2DM 1054
Conclusions and perspectives 1055
References 1055
71 Future Models of Diabetes Care 1058
Introduction 1058
The Chronic Care Model 1059
Health systems 1061
Accountable Care Organizations 1061
Delivery system design 1061
Decision support 1062
Clinical information systems 1063
Self-management support 1064
Community 1064
Telemedicine 1065
References 1066
Index 1069
EULA 1107

Rezensionen

" The undersigned immediately liked that each chapter begins with a summary in the form of key points on a colored background. It makes it possible to foam the text fairly quickly by reading the summary only. Tables and figures also have the same background, making the book clear and easy to read" (direct translation) Journal of the Norwegian Medical Association, Sept 2017

Produkt-Details

• Erscheint lt. Verlag: 6.12.2016
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber ► Gesundheit / Leben / Psychologie
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Diabetologie
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: Diabetes • diabetes, clinical, ADA, EASD, endocrinologist, diabetologist • endocrinology • Endokrinologie • Medical Science • Medizin
• ISBN-10: 1-118-92487-8 / 1118924878
• ISBN-13: 978-1-118-92487-7 / 9781118924877