Diabetes MellitusRenming Hu M.D,PhDDepartment of Endocrinology Huashan Hospital Institute of Endocrinology and Diabetes at Fudan University,Classification of diabetes(ADA-1997),Type 1 (beta-cell destruction, usually leading to absolute insulin deficiency) Autoimmune Idiopathic Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance) Other specific types Gestational diabetes*,Other specific types,Genetic defects of beta-cell function Genetic defects in insulin action Diseases of the exocrine pancreas Endocrinopathies Drug- or chemical-induced Infections Uncommon forms of immune-mediated diabetes Other genetic syndromes sometimes associated with diabetes,Pathogenesis,Pathology,Type 1 DM：inflammation of pancreas Type 2 DM：amyloidosis of pancreas Large vessel ：atherosclerosis Kidney ：diffuse or nodular glomerular sclerosis Retina：arteriolar sclerosis、microaneurysm、exudates、new vessel formation Nerve：axon degeneration 、myelinolysis,Pathophysiology,Abnormalities in metabolism,Carbohydrate ：anabolism ，catabolism、 utilization Lipid ： anabolism ，catabolism ，ketoplasia protein： anabolism ，catabolism ，glyconeogenesis,Insulin secretion curve :normal and diabetics,Clinical Presentation,Natural history of type 2 DM,After the diagnosis of type 2 diabetes: IR constantly existsInsulin secretion ability gradually declines:When FPG reachs the diagnostic criteria，insulin secretion ability has already declined by 50%When FPG7.0mmol/L，-cell insulin secretion ability When FPG1011.0mmol/L，-C insulin secretion ability has already neared absolute deficiency,Models of the onset of two phrases of type 2 DM,NGT IGR(IFG、IGT) DM,cell exhaustion,Insulin resistance,Insulin resistance,WHO plasma glucose guideline,IGT,75gOGTT 2hPG(mmol/L),FPG (mmol/L)7.0 6.1,FPG,7.8 11.1,IGT,Comparison of type 1 and type 2 DM,type1 DM type2 DM Usual age of onset 40years Mode of onset acute chronic weight normal overweight or obesityor weight loss symptoms polyuria,polydipsia, similar but usuallyweight loss less severe presentation Acute complications often few Chronic complications Large vessel disease less then type 2 DM leading cause of death Renal disease leading cause of death 5%10% Insulin and c-peptide low or lack peak value delayed ,high or deficiency Immune marker usually + usually - Therapy insulin dependence oral antidiabetic agents are available,Chronic complications,Macrovascular disease Microangiopathy Diabetic retinopathy Diabetic renal disease Diabetic neuropathy Diabetic dermatopathy Infection,Mechanism of complications,Activation of polyol （or sorbitol）pathway Formation of non-enzyme saccharification products Change of hemodynamics Activation of PKC Microangiopathy theory,Hyperglycemia is the essential reason for diabetic complications,DCCTDiabetes Control and Complications Trial UKPDSUnited Kingdom Prospective Diabetes Study,UKPTS：results,HbA1c 0 .9%，（intensive therapy vs routine therapy）Intensive therapy group: diabetis associated complications 12%，and the fatalness of microvascular complications 25%。 It cannot evidently reduce the incidence of great vessel disease ,such as miocardial infarction and strock . Most stimulating findings：Biguanides can prevent or slow the onset and/or progression of diabetic complications in overweight patients Tight control of hypertension can prevent or slow the onset and/or progression of diabetic complications by 24% （144/82mmHg vs 154/87mmHg） ，stroke by 44%，microvascular complications by 37%。,Epidemiology of diabetes Macrovascular disease,Diabetics are easy to get atherosclerosis Monckebergs sclerosis 41.5 Intimal arteriosteogenesis 29.3 Coronary heart disease、cerebrovascular disease：24 times Risk of miocardial infarction： 10 times Risk of stroke : 3.8 times，especially in women Risk of lower limb amputation：15times ，fatalness,Hypertension in DM,Morbidity rate diabetes: 20%40% Diabetes in EU(35-54years): 30%50% Diabetes in China: 29.2% pathogenesis aortosclerosis Arteriola resistance Hypertension associated with DN Renal hypertension caused by stenosis of renal artery,Diabetic retinopathyleading course of new cases of blindnessPathogeny：state of illness 、course of disease、age of onset5 years ：eyeground disease is not common10 years ：50eyeground disease20 years ：8090eyeground disease,Diabetic Retinopathy,Classifications (China),