1、Diabetes Mellitus,Zhao-xiaojuan,Introduction,Diabetes mellitus is a heterogeneous group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.,Introduction,The chronic hyperglycemia of diabetes is associated with long-term damage, d

2、ysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.,Symptoms,Polyuria Polydipsia (thirst) Weight loss Weakness Polyphagia Blurred vision Recurrent infection Impairment of growth,Criteria for diagnosis of diabetes (WHO1999),Symptoms of diabetes +

3、 Casual plasma glucose 1.1mmol/l(200mg/dl) Or FPG 7.0mmol/l (126mg/dl) Or 2-hPG 11.1mmol/l,Diagnostic Criteria WHO1999,IGT -FPG7mmol/L -2-h PG7.8mmol/L and 11.1mmol/L IFG -FPG6.1mmol/L and 7.0mmol/L,Laboratory Findings,Urinary glucose Urinary ketone Blood glucose (FPG and 2-hPG) HbA1c and FA(fructos

4、amine) OGTT Insulin / CP releasing test,Classification (1),Type 1 diabetes -cell destruction, usually leading to absolute deficiency Immune-mediated diabetes Idiopathic diabetes Type 2 diabetes Ranging from predominantly insulin resistance with relative insulin deficiency to predominantly an insulin

5、 secretory defect with insulin resistance,Classification (2),Other specific types of diabetes Due to other causes, e.g.,genetic defects in insulin action, diseases of the exocrine pancreas, drug or chemical induced Gestational diabetes mellitus(GDM) diagnosed during pregnancy,Etiologic classificatio

6、n of diabetes mellitus(1),I.Type 1diabetes ( -cell destruction, usually leading to absolute insulin deficiency ) A. immune mediated B. Idiopathic II.Type 2diabetes ( may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resi

7、stance ) III.Other specific types A. genetic defects of -cell function 1. Chromosome 12, HNF-1 (MODY3) 2. Chromosome 7, glucokinase (MODY2) 3. Chromosome 20, HNF-4 (MODY1) 4. Mitochondrial DNA 5. Others B. Genetic defects in insulin action 1. Type A insulin resistance 2. Leprechaunism 3. Rabson- Men

8、denhall syndrome 4. Lipoatrophic disease 5. Others C. Diseases of the exocrine pancreas 1. Pancreatitis 2. Trauma / pancreatectomy 3. Neoplasia 4. Cystic fibrosis 5. Hemochromatosis 6. Fibrocalculous pancreatopathy 7. Others,Etiologic classification of diabetes mellitus(2),D. Endocrinopathies 1. Acr

9、omegaly 2. Cushings syndrome 3. Glucagonoma 4. Pheochromocytoma 5. Hyperthyroidism 6. Somatostatinoma 7. Aldosteronoma 8. Others E. Drud- or chemical-induced 1. Vacor 2. Pentamidine 3. Nicotinic acid 4. Glucocorticoid 5. Thyroid hormone 6. Diazoxide 7. -adrenergic agonists 8. Thiazides 9. Dilantin 1

10、0. -Interferon 11. Others F. Infections 1. Congenital rubella 2. Cytomegalovirus 3. Others,Etiologic classification of diabetes mellitus(3),G. Uncommon forms of immune- mediated diabetes 1. “Stiff-man” syndrome 2. Anti-insulin receptor antibodies 3. Others H. Other genetic syndromes sometimes associ

11、ated with diabetes 1. Downs syndrome 2. Klinefelters syndrome 3. Turners syndrome 4. Wolframs syndrome 5. Friedreichs ataxia 6. Huntingtons chorea 7. Laurence-moon-Biedl syndrome 8. Myotonic dystrophy 9. Porphyria 10. Prader-Willi syndrome 11. Others IV. Gestational diabetes mellitus ( GDM ),Patient

12、s with any form of diabetes may require insulin treatment at some stage of their disease. Such use of insulin dose not, of itself, classify the patient.,Type 1 DM,Generally 30 years Rapid onset Moderate to severe symptoms Significant weight loss Lean Ketonuria or keto-acidosis Low fasting or post-pr

13、andial C-peptide Immune markers(anti-GAD,ICA,IA-2),Type 2 DM,Generally 40 years Slowly onset Not severe symptoms Obese Ketoacidosis seldom occur Nonketotic hyperosmolar syndrome Normal or elevated C-peptide levels Genetic predisposition,Pathophysiological model for development of obesity and T2DM,Be

14、ta-cell defect,Intra-uterin growth retardation,Insulin Resistance genes,Obesity genes,Insulin Resistance + Intraabdominal obesity,IGT,T2DM,Western lifestyle,Glucose toxicity,Metabolic Insulin Resistance (FFA),0,80,40,20,60,Year,Disorder of glycemia: etiological types clinical stages,Stages,Types,Nor

15、moglycemia Hyperglycemia,Diabetes mellitus,Type 1 Type 2 Other specific types Gestational diabetes,Normal glucose tolerance,IGT and/or IFG,Not insulin requiring,Insulin requiring for control,Insulin requiring for survival,Acute,life-threatening consequences,Hyperglycemia with ketoacidosis Nonketotic

16、 hyperosmolar syndrome,Microvascular complications,Retinopathy Nephropathy Peripheral neuropathy Autonomic neuropathy,Macrovascular complications,Atherosclerotic cardiovascular disease Peripheral vascular disease cerebrovascular disease,Others,Hypertension Abnormalities of lipoprotein metabolism Per

17、iodontal disease,Potential chronic complications of elevated HbA1c,good,poor,control,RISK,Microalbuminuria Mild Retinopathy Mild Neuropathy,Albuminuria Macular Edema Proliferative Retinopathy Peridontal Disease Impotence Gastroparesis Depression,Foot Ulcers Angina Heart Attack Coronary Bypass Surger

18、y Stroke Blindness Amputation Dialysis Kidney Transplant,The Aims of Treatment,Relief of hyperglycemic symptoms Correction of hyperglycemia, ketonuria and hyperlipidemia Establishment and maintenance of a desirable body weight, and in children normal growth and development Avoidance of acute metabol

19、ic disturbance Prevent or delay the onset of the long-term complications,Targets for control,Management,Essentials of management Monitoring of glucose levels Food planning Physical activity Treatment of hyperglycemia,2.Monitoring of Glucose Levels,Blood glucose levels - before each meal - at bedtime

20、 Urine glucose testing Urine ketone tests (should be performed during illness or when blood glucose is 20mmol/L ),3.Food Planning,Weight control. 50-60%of the total dietary energy should come from complex carbohydrates. 20-25% form fats and oils. 15-20% from protein. Restrict alcohol intake. Restric

21、t salt intake to below 7g/d.,4.Physical Activity,Physical activity play an important role in the management of diabetes particularly in T2DM. Physical activity improves insulin sensitivity, thus improving glycemic control, and may help with weight reduction Do sparingly avoid sedentary activities Do

22、 regularly participate in leisure activities and recreational sports Do every day adopt healthy lifestyle habits,5.Drug Treatment,If the patient is very symptomatic or has a very high blood glucose level, diet and lifestyle changes are unlikely to achieve target values. In this instance, pharmacolog

23、ical therapy should be started without delay.,Treatment,Sulphonylureas Biguanides -Glucosidase inhibitors Thiazolidinediones Glinides Insulin Combination therapy,1.Sulphonylureas,Chlorpropamide Tolbutamide Glibenclamide Glipizide Gliclazide Gliguidone Glimepiride,2.Biguanides,Metformin Phenformin Buformin,3.-Glucosidase inhibitors,Acarbose Voglibose Miglitol,4.Thiazolidinediones,Ro