Clinical Atlas of Diabetes Mellitus Sanjay Agarwal, Arturo R Rolla
INDEX
Page numbers followed by b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
A
Abortion, spontaneous 180
Abscess 233, 236, 238f
Acanthosis nigricans 214, 218, 241, 247, 248f, 249f
of abdomen 252f
of axillae 247f
of dorsum of feet 252f
of knee 251f
of knuckles 250f, 251f
of neck 247f
of wrist 250f
with skin tag 253f
Acanthosis with skin tags 253f
Acarbose 55
Acotiamide 169, 170
Acrochordons 248
Adenosine monophosphate 17, 18
Adipocytes, types of 11
Adipocytic capacitance 11
Adipokines 155
secretion 11
Adiponectin 152
Adipose atrophy 215
Adipose tissue 151, 216
distribution 11
function of 215
insulin resistance 153
Adipositis 10, 216
Adverse cardiac
cerebrovascular event, major 266
events, major 265
Adverse cardio cerebrovascular event, major 270
AKT2 mutation 220
Alanine transaminase 177
Albiglitude 57
All-cause mortality 267
Alogliptin 56
Alpha glucosidase inhibitors 17, 55
Ambulatory continuous glucose monitoring 190
American Association of Clinical
Endocrinologists 22
American Association of Diabetes Educators 58
American College of Obstetricians and
Gynecologists 178, 187
American Diabetes Association 22, 57, 178, 186, 187
guidelines 172
American Geriatrics Society 59
Aminoglycosides 129
Amputation 103, 112
below-the-knee 103, 104
Anemia 88
Angina, unstable 268
Angioplasty plus stents 111
Angiotensin converting enzyme inhibitor 85, 86, 141, 146, 183
Angiotensin receptor blocker 85, 86, 143, 146, 183
Ankle-brachial index 108
Antibiotic
broad-spectrum 130
injections of 221
intravenous 103
Anticholinesterase 169
Antidiabetic drugs 265f
cardiovascular of 263
newer 265
safety of 264
group of 265
Antioxidant activity 158
Antioxidant defenses 154
Antiplatelets 265
Antivascular endothelial growth factor 61
Apgar score 192
Apolipoprotein C3 151
Arterial revascularization therapy study 271
Artery bypass graft 269
Arthrosis 107
Artificial pancreas 41
Aspartate transaminase 156, 177
Asymptomatic bacteriuria 125
Atherosclerosis, pathogenesis of 263
Athlete's foot 236
Atrophy, local 222
Autonomic neuropathy 119
Axillary acanthosis nigricans 249f
severe 217f
Azithromycin 169, 170
B
Bacteremia 133
Bacteriology cultures 99
Balanitis 233, 235, 235f
chronic 235f
Barbiturates 227
Bare metal stent 270
Bariatric procedures 158
Bariatric surgery 11, 158
Barium studies 168
Barraquer-Simons syndrome 222
Basal rate infusions 36
Berardinelli-Seip syndrome 217
Beta blocker 145, 146
Beta cell
dysfunction 13f, 127
mass 12
Bethanechol 169
Biguanides 1618, 54
Bionic pancreas 41
Birth trauma 192
Blocks inhibitory D2 receptor 169
Blood glucose
control 85, 86, 236
for fasting 191
level 109, 184
monitoring, punctures in fingers from 257f
postprandial monitoring of 190
self-monitoring of 59, 189
Blood pressure 51, 82, 140, 145, 183
and neurodevelopment 192
control 85, 86, 148
cuff 140
goals 141, 142b
monitoring of 139
Blood urea nitrogen 109
Blue toe syndrome 112, 241, 258
Body mass index 151, 190
Body weight 9
Borderline perfusion 113
Botulinum toxin 170
Breastfeeding 195
postpartum period 195
Breath tests 168
Breech presentation 194
Brittle diabetes 40
Brown spots 209, 213
Buffalo hump 221f
Bypass angioplasty revascularization
investigation trial 269
C
C3 nephritic factor 221
Calciphylaxis 241, 260, 260f
with finger lesions 261f
with necrotic areas in fingers 261f
Calcium channel blocker 146
Callus
fissure formation in 95f
formation 93f
Canagliflozin 21, 56
Candida 125, 132
albicans 118, 131
Candidiasis 232
Carbuncle 131
Cardiac anomalies, congenital 193
Cardiomyopathy
dilated 263
postpartum 179, 182
Cardiovascular death 267
Cardiovascular disease 47, 142, 263, 270
Cardiovascular risk factors 106
Cardiovascular safety 22
Cardiovascular studies 144
Carotenodermia 231, 232f
Carpenter-Coustan criteria 187
Cataract 75
Cathy Kim image 196f
Cell-mediated immunity 117
Cellular injury 156
Cellulitis 233, 236
Central nervous system 91
defects 180
Cephalosporins 129
Cerebral arteries 113
Cerebrovascular accidents 113
Cerebrovascular disease 47, 106, 113
Cesarean delivery 185
Cesarean section 179, 181
primary 185
Chambers 112
Charcot's disease 104
Charcot's foot 100
Charcot's neuroarthropathy 98f
Cheiroarthropathy 92, 225
Childhood obesity 189
Childhood Z-scores 189
Chloroquine 212
Cholecystitis 127
Cholesterol 51
embolization 112
syndrome 258, 260f
Cilostazol 110
Cisapride 169
Clindamycin 129
Clinical research network system 157
Clostridium hystoliticum 229
Clostridium perfringens 127
Clostridium welchii 127
Cockcroft-Gault equation 82
Cognitive dysfunction 4749
Collagen 225
vascular diseases 227
Colon 165
Combination therapy 22
Complete blood count 177
Congenital malformations 171
Conjunction 189
Cord C-peptide 185
Cornea 74
Coronary artery
bypass surgery 270
disease 146, 263, 270t
revascularization of 269
left anterior descending 272
unprotected left main 270
Coronary by-pass 214f
Coronary physiology 272
Cotton wool spots 63
C-reactive protein 109, 153, 155
Creatinine 109
Cunninghamella species 132
Cushing's syndrome 172
Cystitis 125
Cytokines 155
D
Dapagliflozin 56
Darkening of skin 241, 258, 258f
Deep tendon reflexes 98
Degludec insulin 267
Deoxyfructosyl 33
Depot steroids 221
Depression 4749
Dermatomyositis 227
Dermopathy 209
with diabetes mellitus 209b
Diabetes 47, 57, 74, 106, 107b, 108, 116, 139, 271
and pregnancy 171
epidemiology 173
atypical clinical presentation of 47b
classification 1
comorbidities of 47
control
and complications trial 29, 35, 73, 84
cardiovascular risk in 85
diagnosis of 1, 1b, 24
education 193
effects of 123
infection 116, 119
interventions and complications,
epidemiology of 73, 84
long-term 91
management of infections in 135
nonretinal complications of 74
pathophysiology of 46
progression, type 2 14f
revascularization in 271
reverse 6
skin
infections in 232, 233b
lesions in 209, 209b
traditional complications of 47
treatment of 22, 23, 45, 50
type 8, 76
type 1 171
type 2 8, 12, 13, 14f, 16, 23f, 46, 171, 175
pathogenesis of 9f
vascular complications of 29
Diabetes mellitus 61, 79, 116, 122, 139, 143, 164, 164f, 165t, 209, 218
cardiovascular in type 2 263
cardiovascular of 264
diagnosis of 1
effects of 122
tuberculosis on 124
gastrointestinal complications of 164
incidence in 241b
increased incidence in 241
preexisting 172, 178, 180, 189
risk of 181
type 1 84
type 2 151, 173
Diabetic bulla 229
Diabetic cataracts, reversible 75
Diabetic complications, development of 143
Diabetic dermopathy 213
Diabetic factor consists 92
Diabetic foot 91, 128, 229, 260
advantages 101t
antibiotic treatment 102
disadvantages 101t
general treatment 101
infections 128f
bacteriology of 92b
local treatment 101
pathogenic factors of 104fc
prevention 91b
problems 91, 96
management of acute 99
treatment 101
Diabetic hand 225b
syndrome 225
Diabetic ketoacidosis, recurrent 40
Diabetic kidney disease
diagnosis of 83b
prevalence of 85b
primary prevention of 84
treatment of 86, 86b
Diabetic macular edema
mild 70
moderate 71
severe 71
Diabetic patients
disease in 135
hospitalization of 124
Diabetic retinopathy 61, 66, 67, 71
classification of 64
lesions of 62
level of 66
pathogenesis of 62
progression of 73
study 65f, 66, 71, 72
Diarrhea 170
Diet 11, 52
in renal disease, modification of 82
Dietary approaches to stop hypertension diet 147
Digital sclerosis 225
Dipeptidyl peptidase 266
4 inhibitors 16, 17, 19
Domperidone 169
Dopamine D2 blockers 169
Doppler 108
Dorsum of hand, psoriatic plaques on 256f
Drowsiness 169
Drug eluting stent 270
Dual-energy X-ray absorptiometry 192
Dulaglutide 57
Dunnigan's congenital partial lipoatrophy 221f
Dunnigan's lines 220, 222f
Dunnigan's syndrome 220
Dupuytren's contracture 92, 209, 225, 226, 228f
Dyslipidemia 150, 158
Dyspepsia 170
Dystrophic nails 224f
E
Early treatment diabetic retinopathy study 67
severity levels 66t
Edema 158
Elbow, psoriatic lesions of 255f
Electrocardiogram 177
Electrogastrography 168
Elevated protein kinase C 117
Empagliflozin 56
Emphysematous pyelonephritis 125, 126f
End stage kidney disease 79
Endocrinopathies, manifestation of 172
Endoplasmic reticulum 154
Endotoxins 155
Enteroviruses 127
Epilepsy 227
Eplerenone 147
Erosio interdigitalis 233, 235
Eruptive xanthoma 231, 232f
Erythromycin 169, 170
Escherichia coli 125, 127
Esophageal candidiasis 165
prevalence of 165
Esophageal dysmotility 165
Esophageal motility disorder 165
Esophagus 165
Estimated glomerular filtration rate 80, 82, 83
European Association for Study of Diabetes 22, 57
European Medicines Agency 263
Everolimus eluting stent 270, 271
Exercise 11, 52
Extensor tendons of feet, retraction of 230f
Extrapyramidal syndromes 169
Eye
complications 47
ultrawide field retinal images of 68f, 69f, 72f
Eyelids, skin tags in 219f
F
Fasting and pre-meal glucose 51
Fasting glucose 189
maternal 189
Fasting insulin 189
Fasting plasma glucose 2
advantages of 3t
disadvantages of 3t
Fat but fit 9, 10
Fatal myocardial infarction 267
Fatal stroke 268
Fatigue 13
progressive 13f
Fatty acid 152, 155
intrahepatocellular 153
translocation of 11, 215, 216
Fatty infiltration 216
Fatty liver 218
Fertility and contraception 175
Fetal cardiac hypertrophy 193
Fetal demise 180
Fetal echocardiogram, importance of 193
Fetal heart rate monitoring, continuous 180
Fetal hemoglobin 31
Fetal monitoring during labor, continuous 194
Fetal viability 193
Fibric acid medications 183
Fibrosis 155
stages 157
Fibrous proliferation 64
Flatbush diabetes 15
Flexion tenosynovitis 225
Flexor Babinski's response 98
Flexor tenosynovitis 230f
Fluconazole 165
Foot
and big toe, psoriasis affecting dorsum of 255f
deformities 92
infections 233, 237
inspection 97
Fournier's gangrene 129, 130f
post deroofing 131f
Frameshift mutations 151
Free fatty acid delivery 152
Fructosamine 32
Full-thickness retinal hole formation 70
Fungal cystitis 132
Fungal infection 131, 236
G
Gamma-glutamyl transferase 156
Gangrene 111
Gangrenous complications, cause of 108
Gangrenous tissues 95
Gastric bypass 158
Gastric emptying, scintigraphic
documentation of 168t
Gastroesophageal reflux disease 165
prevalence of 165
Gastrointestinal infections 126
Gastrointestinal system 164
Gastroparesis 40, 165, 166, 166f, 167, 169
diabetic 167, 168f
diagnosis of 167fc
incidence of 165
pathophysiology of 166, 166fc
treatment of 167
Genetically diverse syndromes 172
Genetics 11
Genitourinary infections 124
Genitourinary tract infections 124
Gestational diabetes
diagnosis of 184
mellitus 171, 178, 187, 189, 191, 195, 196
treatment of 189, 192
Ghrelin agonists 169
Glargine 178, 267
Glaucoma 74
Glibenclamide 20
use of 192
Gliclazide 20
Glimepiride 20
Glipizide 20
Glomerular filtration rate 18, 143, 177
Glucagon-like peptide 266
Glucagon-like peptide 1 17
agonists 237
analogs injections 237
Glucagonoma syndrome 209, 222, 224f
Glucagonoma, removal of 224f, 225f
Glucose
loading test 184
monitoring
continuous 40, 41, 50, 58, 178
system, continuous 178
tolerance test 183
Glulisine 178
Glyburide 20, 191, 195
effect of 189
failure 191
instead of insulin 191
use of 189, 192
Glycated hemoglobin level 142
Glycation end products, advanced 117, 118
Glycation, chronic 92
Glycemia 24
alternate markers of 29
Glycemic control 51, 124, 178, 192, 211, 265
tight 135
Glycemic goals and goal setting 51
Glycemic management 178, 192
Glycemic monitoring, punctures from 241, 257
Glycemic status, monitoring of 32
Glycemic targets 171
Glycemic variability 116
Glycohemoglobin 2
Glycohemoglobin A1c
advantages of 3t
disadvantages of 3t
higher levels of 4t
lower levels of 4t
Glycosuria 235
Gynecomastia 169
H
Hammer toes 92, 93f, 229
causes, dorsal retraction of 96f
Hard exudates 64, 67
Hashimoto's thyroiditis 218, 241, 245f
Head and neck infections 119
Headache 170
Heart
defects, congenital 180, 193
failure 146, 158, 263, 266
congestive 82
hospitalization 268
Helicobacter pylori
gastritis 126
infection diabetes 126
Hemoglobin A1c 52, 23, 176
Hemolytic anemia 218
Hemorrhages 63, 68f
extensive preretinal 69f
preretinal 70
Hepatic
fibrosis 155
inflammation 152
steatosis 155
stellate cells 152
Hepatitis
B 127
C virus 127, 133
direct effects of 127
chronic active 218
Hepatobiliary infections 126
Hepatocellular carcinoma 156
Hepatocyte 152, 156
ballooning 156, 157
death 155
Hereditary hemochromatosis 258f
Hidradenitis suppurativa 233, 237
High performance liquid chromatography 30
High-density lipoprotein 150
cholesterol 189
Hirsutism 218
Home blood pressure 140, 141
monitoring 140
Human immunodeficiency virus 121, 133, 222
Humoral immunity 117
effects on 118
Hydrogen peroxide 154
Hydrolytic enzymes 151
Hydroxychloroquine 212
Hydroxyl 154
Hyperaldosteronism, primary 147, 148
Hyperbaric oxygen 102
therapy 130
Hyperbilirubinemia 179, 186
Hyperglycemia 13, 50, 82, 165, 172, 179, 180, 181, 185, 263
acute complications of 51
affects 116
complications of 16
increases, chronic 225
maternal 179, 181, 194
transient 124
Hyperinsulinemia 215
Hyperlipidemia, severe 230
Hyperparathyroidism 88
Hypertension 84, 139, 145, 179, 182
chronic 182, 183
management, importance of 139
monitor 139
pregnancy-induced 179
secondary causes of 147b
Hypertensive hemorrhages 113
Hypertriglyceridemia
familial 183, 231
postprandial 151
Hypertrophy, local 222
Hypoadiponectinemia 155
Hypoaldosterone renal tubular acidosis 148
Hypoglutathionemia 155
Hypoglycemia 22, 40, 50, 51b, 179
frequent 40
infant 195
maternal 192, 193
neonatal 179, 181, 185, 186, 192
prevalence of 193
recurrent 30
severe 35, 40, 178, 193
Hyporenin 148
Hypothenar areas of palms, puncture
marks in 257f
I
Immune perturbation 116, 121
functional pathology in 117t
Impaired fasting
glucose 5
glycemia 45
Impaired glucose tolerance 5, 45
Indian Diabetes Risk Score 157
Infection 95
causes predisposing to 117fc
lower extremity 128
Inflammation 155
Inflammatory cells 152
Inflammatory cytokines 117, 124
effects on 118
Influenza 124
Inguinal intertrigo 234f
Insulin 58, 153, 191, 192
delivery 36
hematomas 238f
injection 237, 238f
chronic 221
site acanthosis 238f
lipoatrophy 239f, 240f
areas of 239f
lipohypertrophy 240f
in thighs 240f
pump 35
advantages of 40
disadvantages of 40
therapy 35, 38, 39, 41
purification of 221
receptor substrate phosphorylation 152
resistance 8, 10, 152, 158, 171, 172, 174, 215, 218
clinical components of 12f
severe 39
secretagogues 20, 54
severe 215
signaling 127
Integrated glucometer and remote control 38
Intensive neonatal care 186
Intergluteal intertrigo 234f
Intermittent claudication 107
differential diagnosis of 109
moderate 109
International Association of Diabetes and
Pregnancy Study Groups 183, 187
International Classification of Diabetic
Retinopathy 66, 68, 69
International Clinical Diabetic Retinopathy and
Diabetic Macular Edema Scale 66t
International Diabetes Federation 58
International Federation of Clinical Chemistry
Reference Measurement Procedure 30
International Federation of Gynecology and
Obstetrics 186
International Verapamil SR-Trandolapril Study 142
Interphalangeal joint 93, 230f
first 92
of toes 93f
Interstitial cells 166
Interstitial fluid 190
Intertrigo 232, 233, 233f
chronic 234f
with psoriasiform scales, chronic 234f
Intraretinal microvascular abnormalities 63, 67
Intrauterine fetal demise 172, 179, 180
Intrauterine growth retardation 179, 181
Iris 74
Ischemia 91, 260
Islet cell dysfunction 11
Itopride 169
J
Joint National Committee 183
Joslin guidelines for gestational diabetes
mellitus 188fc
K
Kaposi's sarcoma 241, 258
lesions in wrist, classical 259f
with beefy lesions in wrist, classical 259f
with lesions in toes, classical 259f
Ketoacidosis 265
diabetic 17, 35, 177, 179, 180
Ketonemia 180
Kidney disease 83b, 142, 269
chronic 40, 79, 80, 88146, 182
development of 83
diabetic 79, 81, 82b, 143
Klebsiella 125, 127
Köbberling syndrome 220
Kobner reaction 255
Kupffer cells 152, 155
L
Labor and delivery 194
Large for gestational age 180
Latent autoimmune diabetes 15
Latent infection 122
Lawrence syndrome 218
Leg
brown spot in 214f
psoriatic plaques in front of 255f
Lens 75
Leukotrichia 245f
Levosulpiride 169
Levothyroxine 194
Limb ischemia
acute 111
severe 108
Limited joint mobility 209, 225
syndrome 225
Linagliptin 56
Lipid accumulation 211f
Lipoatrophic diabetes 220f
acquired generalized 219f
congenital 217f
generalized 216f, 217f
phlebomegaly in 223f
with muscle hypertrophy 219f
with phlebomegaly 220f
Lipoatrophy 209
Lipodermatosclerosis 114
Lipodystrophy 214, 215, 218b
acquired
generalized 218, 219b
partial 220, 222b
complications of 218b
congenital
generalized 217, 218b
partial 219, 220b
with enophthalmos, acquired 219f
Lipohypertrophy in abdomen 239f
Lipoidica 210
Lipoproteins, circulating 150
Lipotoxicity 215
Liraglutide 57
injection 241f
Liver
disease 31
function test, abnormal 156
insulin resistance 152
Lixisenatide 267
Lobular inflammation 156, 157
Low birth weight 11
Lower blood pressures 144
Lower limb amputations 112
Lymphocytes, effects on 118
M
Macrosomia 179, 180, 194
Macrovascular complications 126
Macula 70
Macular edema 70
diabetic 62, 6467, 70, 72
Male genitalia 129
Maturity onset diabetes of young 15
Mean plasma glucose 29
Medical nutrition therapy 171, 175, 177, 189
Meglitinide 17, 20, 55
analogs 20
Melanin pigmentation 213
Metabolic abnormalities 214, 221
serious 215
Metabolic alterations, lesions due to 230, 231b
Metabolic dysfunction 189
Metabolic pathway, effects on 116
Metabolic rate, increased 218
Metabolic syndrome 11, 12f, 158
risk of 181
Metacarpophalangeal joints 226f
Metatarsal
bones, heads of 94f
joint 94f
phalangeal joint 94f
Metatarsophalangeal joint, first 94f
Metformin 11, 54, 191, 192, 195
group 191, 192
in gestational diabetes trial 191
Methicillin-resistant Staphylococcus aureus 128
Metoclopramide 169
Metronidazole 129
Microalbuminuria 126, 182
development of 143
Microaneurysms 63
Microsomes 154
Microvascular angina 263
Microvascular disease 263
Miglitol 55
Miscarriage 179, 180
higher rate of 180
Mitochondrial deoxyribonucleic acid 154
Mitochondrial oxidative 110
Monitoring glycemic control 29
Monooxygenases 154
Mosapride 169
Motilin receptor agonists 169
Mucor 132
Mucormycosis 132
intraoperative photos of 132f
Multiple basal
patterns 36
rate 36
Multiple daily injections 178
Multiple skin tags 253f, 254f
Muscarinic agonist 169
Mycobacterium tuberculosis 122
Myocardial infarction 146, 179, 182, 266, 270
Myofibroblastic phenotype 155
N
Naftidrofuryl 110
Nail dystrophy, improvement in 225f
Nails in psoriasis, pitting of 256f
Nateglinide 55
National Diabetes Data Group 184, 187
National Glycohemoglobin Standardization
Program 30
National Health and Nutrition Examination Survey 80, 152
National Institute for Health and Care
Excellence 176, 178
National Institute of Diabetes and Digestive and Kidney Diseases 156
National Institutes of Health 186
Necrobiosis lipoidica 209, 211f, 212f, 214f
complicated with
infection 213f
ulcerations 213f
in initial stages 210f
with infected ulcerations 213f
Necroinflammation 156
Necrolytic migratory erythema 222, 224f
disappearance of 224f
Necrotic toe 260f
Necrotizing fasciitis 129, 130f
Neonatal intensive care unit 192
Neostigmine 169
Neovascularization 64
Nephrology 88
Nephropathy 182
progression of 179
Nerve palsy 74
Neurological examination 97
Neuropathy 91, 126
Neutrophils, effects on 118
Newer antidiabetic drugs 266t
Niacin 183
Non-adipocytic cells 11
Nonalcoholic fatty liver disease 150155, 157
causes of 150
management of 158
pathogenesis of 152
Nonalcoholic steatohepatitis
grading of 157t
staging of 157t
Non-enzymatic glycation 225
Non-fatal
myocardial infarction 267
stroke 268
Nonproliferative diabetic retinopathy 64, 66, 67, 68, 68f, 71
lesions 65f
severe-very severe 62
Non-traumatic amputations 269
Nutrition 193
O
Obesity 10f, 150, 171, 181
abdominal 9
prevalence of 173
Olmesartan 143
Omega-3 fatty acids 183
Onycholysis in psoriasis 256f
Onychomycosis 236
Optimal medical
therapy 269
treatment 270
Oral agents, classification of 16
Oral and esophageal candidiasis 131
Oral antidiabetic
agents 16
drugs 16t, 17t
classification of 16
Oral glucose tolerance test 2, 4
advantages of 5t
disadvantages of 5t
Oral hypoglycemic
agents 135
treatment 191
Osteomyelitis 103
Otitis externa, malignant 120, 120f
Oxidative stress 117, 152, 154, 155
P
Pain, chronic 47, 50
Palmar fascia fibromatosis 225
Palmar fibrosis 226f, 227
Palmar sclerosis 209, 225, 226f228f
Palpable petechiae 112
Pancreatitis 183
acute 218
hypertriglyceridemia-induced 183
Paracrystalline inclusions 153
Parafoveal capillaries, nonperfusion of 70
Paranasal sinuses 134f
Parathyroid hormone 88
Particular muscular group 107
Pedis foot 236
Penicillin 129
Percutaneous coronary intervention 270
Percutaneous transluminal coronary
angioplasty 270
Perilipin-1 gene 151
Perimuscular fat and phlebomegaly, loss of 220f
Perinatal mortality 179
rate 179
Perinephric abscesses 126
Periodontitis 121, 121f
Periorificial vitiligo 244f
Peripheral arterial disease 106
Peripheral vascular disease 47, 92, 99, 104, 106, 108, 109, 129, 263, 269
disabling 110
Peroxisome 154
proliferator activated receptor 17, 18, 153
Pharmacotherapy 53
Phenytoin 227
Phospholipase domain-containing protein 3 151
Phytobezoars 167
Pioglitazone 55, 158, 264
Placental insufficiency, markers of 193
Plantar Dupuytren's contracture 227, 229f
Plantar subcutaneous tissue, decreased 97
Pneumonia 124
Polycystic ovarian syndrome 171, 218
Polyhydramnios 181
Polyol pathway shunting 117
Polypharmacy 47, 48, 49
Polyuria 46
Poor glycemic control 181
Postpartum period medical management 195
Postreceptor insulin signaling 174
PPARG mutation 220
Praying sign 226, 227
Preconception insulin resistance 174
Preconception period medical nutrition
therapy 176
Prediabetes 4
Preeclampsia 182, 185, 193, 194
Pregnancy 82, 183
complications 171, 179
nondiabetic 190
Prenatal care 193
Prenatal vitamin supplementation 172
Preterm delivery 179, 181, 185
Preterm labor 181
increased risk of 181
Profibrogenic cytokines like interleukin-10 152
Proinflammatory cytokine secretion 155
Prokinetics 167
Proliferative diabetic retinopathy 62, 64, 65, 65f, 6669, 69f, 71, 72f
Protein carbonyl content 154
Proteus 125
Protruding interphalangeal joint 95f
Prucalopride 169
Pseudomonas aeruginosa 120
Psoralen, local 212
Psoriasis 241, 252
Psoriatic arthritis, acute 255f
Pump delivers insulin 36
Pyelonephritis 125
uncomplicated 126
Pyloromyotomy, endoscopic 170
Pyloroplasty, surgical 170
Q
Quinapril 141
R
Radiological manifestations, effects on 122
Radionuclide gastric emptying scintigraphy 168
Radionuclide scanning 120
Ramadan fasting 40
Randomized controlled trial 38
Red blood cells 31
Renal artery stenosis 147, 148
Renal disease 182
Renal failure, chronic 97
Renin-angiotensin-aldosterone system 85, 86, 146
Repaglinide 55
Respiratory tract infections 121
Resting pain, treatment of 111
Retinopathy
progression of 179, 182
severity 66
Rheumatoid arthritis 218
Rhizopus 132
oryzae 133
Rifampicin 124
Rosiglitazone 55
S
Salmonella enteritidis 127
Saxagliptin 56
Scatter laser photocoagulation 71
Scleredema 209, 227, 229
Secretion of anti-inflammatory cytokines 152
Sedimentation rate 109
Self-monitoring programs 59
Sensor augmented pump therapy 37
Sensory neuropathy 91, 119
Serum leptin levels, low 218
Several cardiometabolic risk factors 150
Severe neonatal hypoglycemia, prevalence of 192
Shin spots 213
Shoulder dystocia 179, 186
Signaling pathway, effects on 116
Simple steatosis 156
Sirolimus eluting stent 270
Sitagliptin 56
Skin
and skin lines, blanching of 228f
bacterial infections of 236
candidiasis 236
complications of treatments 237, 237b
diffuse darkening of 258f
dryness 236
in center, atrophy of 212f
infection 128
irritation 94
lesions 241, 214b
tags 241, 248, 254f
thinness 236
Small dense low-density lipoprotein 154
Small for gestational age 181
Small intestinal bacterial overgrowth 165
Smartguard insulin pump 38f
Smartguard technology 37
Sodium glucose 266
co-transporter 2 17, 21, 265
Soft exudates 63
Soft tissue infection 128
Sphygmomanometer 140
Spironolactone 147
Sputum positivity 122
Staphylococcus aureus 102
Staphylococcus-resistant 102
Stasis dermatitis 236
Statin 183
Steatohepatitis 152
nonalcoholic 150
Steatosis 156
grade 157
progresses 152
Stellate cells 155
Stenosing tenosynovitis 92
Sterol regulatory element-binding proteins 153
Stomach 165
Stress
diabetes, acute 3
peripheral vascular studies 109
Subcutaneous arterioles 260
Subcutaneous skin 214
Subcutaneous tissue 210, 214, 215
Submammary skin tags, multiple 254f
Sulfonylurea 17, 20, 21, 54, 237
receptor 20
Superoxide 154
Suppress liver inflammation 155
Systemic hypertension 264
prevalence of 264
Systolic blood pressure 144
intervention trial 144
T
Tenosynovitis 92, 225
Therapy, cost-effectiveness of 24
Thiazolidinedione 11, 1618, 55, 264
Thiobarbituric acid reactive substances 154
Thrombophlebitis 170
Thrombosis, local 113
Thyroid
disorders 183
hormone replacement 183
stimulating hormone 177, 194
Tight glycemic control 179
Toes 92
Transcutaneous oxygen measurements 109
Transient ischemic attacks 113
Transpyloric stent placement 170
Triglycerides 189
Tropical hand syndrome 128, 129f
Truncal obesity 9
Truven health marketscan database 173
Tuberculosis 121
risk factor for 122
treatment response in 123
Tumor necrosis factor 211
alpha, plasma levels of 155
Two-hit hypothesis 152
U
Ulcer 128
Ulcerated plaque 112, 113
Ulceration
chronic 214f
severe 100
United Kingdom Prospective Diabetes Study 73, 85
United States Joint National Committee 144
Unstable angina, significance of 268
Urinary incontinence 47, 50, 234f
Urinary tract infection 17, 82, 125
Urine albumin level 82b
US Food and Drug Administration 263
V
Vascular examination 99
Venous ulcers 114
Verrucous’ appearance 251f
Very low-density lipoprotein 150, 154
Vibratory sensation 97
Visceral adipose tissue 152
Vision
and hearing loss 45
loss, moderate 65
Vitiligo 241, 242f
elbow on 243f
in dorsum of hands and fingers 243f
of glands and prepuce 247f
of nipple 246f
of penis 246f
of scrotum 246f
of surgical scar 244f
on dorsum of feet 244f
on knees 243f
over anterior neck 245f
over arm and forearm 245f
with well-delineated borders 242f
typical lesions of 242f
Voracious appetite 218
Vulvovaginitis 233, 235
W
Waist circumference 189
Waist-to-height ratio 189
Watershed perfusion 113
Weight
gain 22, 158
loss 11, 158
Wet gangrene 111
Wireless motility capsule 168
X
Xanthelasma palpebrarum 231
Xanthoma 230, 231, 231f
Z
Zonal location and severity 157
×
Chapter Notes

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Diabetes: Diagnosis and ClassificationCHAPTER 1

Arturo R Rolla
When Aretaeus of Cappadocian described and coined the term “diabetes”, he was describing excessive urination (“…it is impossible to put any restraint to the patient's drinking or making water”). Nowadays diabetes means increased levels of blood glucose, the marker of many different diseases with different etiologies and mechanisms that have in common hyperglycemia and, in many cases, the long-term consequences of the disease. By now, high levels of blood sugar are easily treated and it is very rare to die directly from it, but the consequences of uncontrolled diabetes and its associated problems result in a large number of blindness, renal failure, amputations, and especially cardiovascular problems. Diabetes is bad because it is diabetes but it is worse because of the bad companies it keeps!
The diagnosis of diabetes mellitus-1 (DM-1) is usually straight forward because the blood sugar levels are quite high, has a rapid onset, and the patients are symptomatic. DM-2, on the other hand, has an insidious onset, mostly asymptomatic, and frequently is an incidental finding during a routine physical examination (Box 1.1). The transition from normal to pre-diabetes and then to established diabetes is slow and may have improvements and aggravations over the years. During this gradual aggravation of the metabolic process, some of the complications including the cardiovascular may have already started even though the diagnostic glycemic levels may not have been reached, or have not been found.
2These diagnostic criteria are general guidelines indicating important steps in the pathogenesis of diabetes but the patient has to be considered as a whole—not just an isolated blood glucose value—contemplating also past medical and family history, associated conditions, and cardiovascular risk factors (Box 1.2). In patients at risk the time for medical intervention should be much earlier that in the past.
The diagnostic criteria at the present time are based on the determination of fasting plasma glucose level, glycohemoglobin A1c, and/or less common, an oral glucose tolerance test (OGTT). Each one of these methods has advantages and disadvantages, with variable clinical acceptance depending on their availability and reliability in different parts of the world. Thiazide diuretics, glucocorticoids and atypical antipsychotic medications should be taken into consideration while performing these tests.
Fasting plasma glucose can be obtained with dependable results in most of the world, but note that for diagnostic purposes the plasma glucose must be measured in a laboratory with well calibrated instruments. Home glucose meters measure whole blood glucose and have a variability range of 10–15% or more in the same sample so that they are absolutely not recommended for diagnosis, and they should be used only for glycemic control. It may sound redundant but we urge you to find the best available laboratory to do these tests, and it is always wise to repeat the test on a different day – and may be in a different laboratory. The fasting plasma glucose is a direct indication of the hepatic glucose production that occurs during the night and with the “Dawn phenomenon”, which are exaggerated because of insulin resistance at the level of the liver.
The advantages and disadvantages of fasting plasma glucose are listed in the Table 1.1.
Glycohemoglobin A1c: Initially, after its standardization, it seemed to be a better and more simple test to diagnose diabetes but it was later found to be not as sensitive as the fasting plasma glucose determination. There are about 30% of patients with elevated fasting plasma glucose who have a hemoglobin A1c less than 6.5%.
3
Table 1.1   Advantages and disadvantages of fasting plasma glucose.
Advantages
Disadvantages
  • Technically very simple
  • Extensive experience and standardization
  • Availability all over the world
  • Inexpensive
  • Criteria are well known and accepted
  • Correlations with complications are well established
  • Requires fasting for at least 8 hours (Not always done by the patients)
  • May need an extra visit
  • Value reflects only one metabolic moment
  • Acute illness may increase values
  • Many technical variables (Time to perform, intra-specimen and day to day variations)
  • Does not represent prandial values
Table 1.2   Advantages and disadvantages of glycohemoglobin A1c.
Advantages
Disadvantages
  • Standardized by the diabetes control and complication trial (DCCT)
  • May be obtained at any time of the day
  • Does not require fasting
  • Less biological variability
  • More stable in a vial
  • An index of 3 months of previous glycemic control
  • Represents both fasting and post-prandial levels
  • Not affected by acute illness
  • Criteria well known and accepted
  • Proven association with control and complications
  • Not available in certain parts of the world
  • More expensive
  • Not reliable with some hemoglobinopathies, anemias, transfusions, and variable half-life of red blood cells in circulation
  • Hypo and hyper “glycators”, higher values in African-Americans
  • Lower levels in advanced renal disease
  • Not validated for children and adolescents
On the other hand, it is quite specific, and in most clinical situations it has very rare false positives. One advantage is that it represents the previous glycemic levels of about three months. This becomes very useful in situations of hyperglycemias found in acutely ill patients (Infections, acute myocardial infarctions, surgery, trauma etc.) who were not known to have diabetes (Table 1.2). The differential diagnosis is between an unknown diabetes of longer duration, or an acute “stress” diabetes. If the level of hemoglobin A1c is elevated it indicates that the patient has had diabetes in the past. If the level of A1c is normal it becomes a clear indication of acute “stress” diabetes. But, there are some disadvantages also which are listed in the Table 1.2.
The process of hemoglobin glycation is non-enzymatic and depends on the level of hyperglycemia, time, and a less known factor that is the rate of glycation of each protein. The longer the red cells stay in circulation and the higher the glycemic levels, the higher the A1c. The attachment of glucose to the hemoglobin seem to be different in some individuals, and there “High Glycators” (Highher A1c levels for the same levels of glycemia) and “Low Glycators” (Table 1.3).4
Table 1.3   Higher levels and lower levels of glycohemoglobin A1c.
Higher levels
Lower levels
  • “High glycators”, African-Americans
  • Increasing age
  • Some hemoglobinopathies
  • Iron and B12 deficiency anemias
  • Post-splenectomy because of more prolonged half-life of the red cells. Note that this is very common after a pancreatectomy because frequently it is necessary to remove the spleen during this surgery
  • Systemic inflammation (CRP, neutrophil and monocyte elevations)
  • Alcoholism
  • Chronic renal failure
  • Hyperbilirubinemia
  • Large doses of aspirin
  • Chronic opiate use
  • “Low glycators”, probably genetic
  • Shortened red blood cell half-life, hemolytic anemias
  • Acute anemias with high reticulocyte count
  • Erythropoietin administration
  • Some hemoglobinopathies
  • Antiretrovirals and dapsone
  • Hipertriglyceridemia (Technical problem in the assay)
Oral Glucose Tolerance Test (OGTT): It is still used in some parts of the world as the gold standard for the diagnosis of DM-2, and is routinely used for the diagnosis of gestational diabetes (Although with a different technique). Again, the measurements should be as plasma glucose, and done with laboratory equipment. It is very sensitive, and gives a very good idea of both fasting and post-prandial levels but it requires a prolonged visit, at least two venipunctures and the ingestion of a standardized glucose load of 75 g. Usually two samples are obtained, fasting and two hours. Plasma glucose levels at one hour are usually not necessary since they are highly variable according to the rate of gastric emptying. Blood sugar levels two hours after a glucose load are mostly related to the prandial insulin secretion of the beta cells, particularly to the first phase that normally prepares the cells to take up the carbohydrates coming from the intestinal absorption. Occasionally, patients become nauseated and are unable to drink the entire volume, or they start vomiting. In these cases, the test should be stopped and repeated two or three weeks later.
Each test has advantages, disadvantages and pitfalls so that they have to be utilized according to the patient and their availability and reliability in every part of the world (Table 1.4). With any of the tests if the results are inconclusive or the patient is at high-risk, it is important to repeat the same test or obtain another one to confirm or not the diagnosis. Even with one positive diagnostic test, it is recommended to obtain a confirmation with the same or one of the other tests.
 
PREDIABETES
DM-1 is preceded by a prediabetic state that may last for several years, and is only diagnosed by checking the specific autoantibodies. Not all the individuals with positive antibodies will develop this form of diabetes. The more positive antibodies, the more the likelihood of developing DM-1.5
Table 1.4   Advantages and disadvantages of the oral glucose tolerance test.
Advantages
Disadvantages
  • Well standardized
  • Very sensitive
  • Measures both fasting and postprandial levels
  • May be positive even when the fasting plasma glucose is normal (Abnormal Glucose Tolerance)
  • Requires fasting- More inconvenience for the patient, (Prolonged visit, repeated venipunctures, nausea or vomiting with the glucose drink)
  • Day-to-day variability
  • More expensive
  • Gastrointestinal factors (Gastrectomy, gastroparesis, malabsorption, etc.)
DM-2 also has a very prolonged and asymptomatic prediabetic stage that is characterized by insulin resistance and beta cell hypersecretion initially completely euglycemic. The progression from normoglycemia to dysglycemia may be faster for certain ethnic groups like Asian-Indians. Once the process of beta cell fatigue ensues—usually starting with the loss of the first phase of prandial secretion—progressive increases in glycemic levels appear. There are fluctuations in these metabolic parameters but, if there are no lifestyle or therapeutic interventions, the glycemic levels slowly increase to attain diagnostic levels. Lifestyle modifications, especially weight loss, at this stage can prevent the progression towards diabetes, but they are not easy to implement and maintain over the years. Earlier screening and diagnose permits better results in prevention and in future treatments. Also, the higher the levels of any of these tests there is a continuous increase in the risk of new diabetes.
Diagnostic criteria for prediabetes are discussed in the Box 1.3.
 
IMPAIRED GLUCOSE TOLERANCE
Impaired glucose tolerance is a prediabetic stage characterized by a 2-hour plasma glucose level between 140 and 199 mg/dL (7.8 and 11 mmol/L) during an OGTT. It indicates a failure of the beta cell secretion after a meal, particularly a decrease or absence in the first phase, and accompanied also by delayed hypersecretion due to the persistent post-prandial hyperglycemia.
Impaired fasting glucose is diagnosed when the fasting levels are between 100 and 125 mg/dL (5.6–6.9 mmol/L) and it represents mostly inappropriately increased hepatic glucose 6production during an overnight fast. It is not uncommon for patients with DM-2 after the disease has been diagnosed to have fasting glucose levels that are higher than during the rest of the day (“Reverse diabetes”). This explains why the determination of fasting glucose levels is so sensitive for the diagnosis of diabetes. Individuals with impaired fasting or glucose tolerance have a risk of developing new diabetes at a rate of 5–10% per year. The risk is even greater when both abnormalities are present. Nevertheless, impaired glucose tolerance tends to be more frequent, and has a greater association with cardiovascular mortality later on.
Increased glycohemoglobin A1c: Prediabetes may also be diagnosed with levels of A1c between 5.7 and 6.4%, with the risk increasing with values closer to 6.5%. Again, the determination of A1c is not as sensitive as the other methods for the diagnosis of prediabetes.
Our scientific knowledge has progressed enormously with the new tools of genetics and molecular biology in the last few years but we still have a lot to learn. With the discovery of the genomic sequence many of us thought that we soon will be able to understand the predisposition, causes and mechanisms of many common conditions. So far, only very few, uncommon, usually monogenic, diseases have been elucidated leaving the majority of the common clinical problems we see daily in our clinics and hospitals still without clear explanations. We desperately need ways to understand the different types and etiologies of the diabetes that today we simply classify as type 1 and type 2. In particular, we urgently need simple methods to quantify insulin resistance and beta cell mass in our patients to be able to direct our treatments according to the particular mechanisms that are abnormal in each patient.
An important stimulus to try to diagnose diabetes earlier has to do with the protection of the beta cells. Blood glucose control is much better and easier when there is a considerable residual mass of beta cells in the pancreatic islets able to secrete variable amounts of insulin. The more functioning beta cells the less hyper- and hypoglycemia our patients will have. Aging, glucose toxicity, chronic hypersecretion, fatigue and apoptosis keeps decreasing the viable beta cells in the pancreas day by day. In DM-1, we have to add the autoimmune attack or insulitis. The earlier we intervene to normalize the blood glucose levels and avoid the fatigue caused by the constant hypersecretion the more beta cells that we save for the future. At the same time—even though we still do not know exactly the mechanisms—euglycemia improves insulin resistance, which in turn helps to put the beta cells to rest decreasing their tendency to fatigue. Recent epidemiological studies in Europe have shown that earlier diagnosis and intervention are more important than the improvements later obtained in glycemia, blood pressure and lipid control.
Prevention and early diagnosis: We all know that the best treatment is prevention but at the present time we are still waiting too long to diagnose and treat DM-2. It is relatively easy for an experienced physician to forecast the appearance of hyperglycemia in an obese, sedentary individual with a strong family history of diabetes, several components of the metabolic syndrome, polycystic ovaries, or with a past history of gestational diabetes. Approximately, 50% of persons with DM-2 around the world are undiagnosed. Why do we have to wait for the blood glucose or the glycohemoglobin A1c to increase above an arbitrary level when we know that at the time of the diagnosis of type 2 diabetes half of the patients (in developed countries where they have more frequent medical encounters and interventions) already have signs and 7symptoms of chronic complications and the blood vessels show already changes of arteriosclerosis?
BIBLIOGRAPHY
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