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Diabetes mellitus

Diabetes mellitus. Zhang jin-an ( 张进安） Endocrinology Department of the First Affiliated Hospital, Medical College, Xi’an Jiaotong University. Diabetes mellitus. Diabetes mellitus (DM) : a syndrome Factors contributing to hyperglycemia may include

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Diabetes mellitus

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  1. Diabetes mellitus Zhang jin-an (张进安） Endocrinology Department of the First Affiliated Hospital, Medical College, Xi’an Jiaotong University

  2. Diabetes mellitus Diabetes mellitus (DM) : a syndrome Factors contributing to hyperglycemia may include DM causes secondary pathophysiologic changes

  3. Prevalence In China, 1980: 0.67% 1994: 2.51% 1996: 3.21% In the world, 1997: 135 million 2000: 175 million 2025: 300 million

  4. Diabetes mellitus result in • DM is the leading cause of blindness between the ages of 20 and 74 in the United States • Diabetic nephropathy is the leading cause of ESRD in the United States and a leading cause of DM-related morbidity and mortality • DM is the leading cause of nontraumatic lower extremity amputation in the United States. • coronary heart disease events and mortality are two to four times greater in patients with type 2 DM

  5. Severe economic load of diabetes mellitus Medical cost of DM in USA (100million USD per year)

  6. Etiologic Classification of Diabetes Mellitus • I. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency)  A. Immune-mediated  B. IdiopathicII. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance)III. Other specific types of diabetesIV. Gestational diabetes mellitus (GDM)

  7. III. Other specific types of diabetes A. Genetic defects of β-cell function characterized by mutations in: • Hepatocyte nuclear transcription factor (HNF) 4α (MODY 1) • Glucokinase (MODY 2) • HNF-1α (MODY 3) • Insulin promoter factor (IPF) 1 (MODY 4) • HNF-1β (MODY 5) • NeuroD1 (MODV6) • Mitochondrial DNA • Proinsulin or insulin conversion •  B. Genetic defects in insulin action • Type A insulin resistance • Leprechaunism • Rabson-Mendenhall syndrome • Lipodystrophy syndromes • C.Diseases of the exocrine pancreas—pancreatitis, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, fibrocalculous pancreatopathyD.Endocrinopathies—acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronomaE.Drug- or chemical-induced—Vacor, pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, diazoxide, β-adrenergic agonists, thiazides, phenytoin, α-    interferon, protease inhibitors, clozapine, beta blockersF.Infections—congenital rubella, cytomegalovirus, coxsackieG.Uncommon forms of immune-mediated diabetes—“stiff-man” syndrome, anti-insulin receptor antibodiesH.Other genetic syndromes sometimes associated with diabetes—Down's syndrome, Klinefelter's syndrome, Turner's syndrome,    Wolfram's syndrome, Friedreich's ataxia, Huntington's chorea, Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-    Willi syndrome

  8. Classification: (ADA 1997) 1. Type 1 diabetes: absolute INS deficiency (Immune mediated, Idiopathic) 2. Type 2 diabetes: INS resistance and relative INS deficiency 3. Other specific types: cause is clear 4. Gestational diabetes: during pregnancy determine if DM after 6 ws of delivery.

  9. Etiology and pathogenesis 1. Type 1 DM : (1) genetic factors: concordance in identical twins50% HLA-DR3,DR4 (+), DQA1*0102, DQB1*0602(-) at least 17 different geneticloci (2) autoimmune factors: insulitis: CD4+/CD8+, IL-1,TNF-α, IFN-γ ICAs(GAD, insulin, IA-2) (3) environment factors: virus infection: Coxsackie B, mumps chemicals: vacor, streptozotocinum; diet: bovine milk proteins

  10. H.E ICA(-) ICA(+)

  11. Type 2 DM: (1) genetic factors: ---concordance inidentical twins 70~90% --- Various genetic loci (2) Environment factors: obesity: high calorie diet, less exercise INSULIN RESISTANCE (a) result: impairs glucose utilization; increases hepatic glucose output (b) molecular mechanism: postreceptor defects (Polymorphisms in IRS-1;GLUT4 ) IMPAIRED INSULIN SECRETION (a) Heavy burden to islet cell (b) amyloid fibrillar deposit in islet (c) glucose toxicity (d) lipotoxicity

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