Diabetes Mellitus

1. Diabetes Mellitus Zhao-xiaojuan

2. Introduction • Diabetes mellitus is a heterogeneous group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

3. Introduction • The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

4. Symptoms • Polyuria • Polydipsia (thirst) • Weight loss • Weakness • Polyphagia • Blurred vision • Recurrent infection • Impairment of growth

5. Criteria for diagnosis of diabetes (WHO1999) Symptoms of diabetes+ • Casual plasma glucose ≥ 1.1mmol/l(200mg/dl) Or • FPG ≥ 7.0mmol/l (126mg/dl) Or • 2-hPG ≥ 11.1mmol/l

6. Diagnostic Criteria WHO1999 • IGT -FPG<7mmol/L -2-h PG≥7.8mmol/L and <11.1mmol/L • IFG -FPG≥6.1mmol/L and <7.0mmol/L

7. Laboratory Findings • Urinary glucose • Urinary ketone • Blood glucose (FPG and 2-hPG) • HbA1c and FA(fructosamine) • OGTT • Insulin / CP releasing test

8. Classification (1) • Type 1 diabetes β-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 secretory defect with insulin resistance

9. 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 diabetesmellitus(GDM) diagnosed during pregnancy

10. Etiologic classification 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 resistance ) 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- Mendenhall 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

11. Etiologic classification of diabetes mellitus(2) D. Endocrinopathies 1. Acromegaly 2. Cushing’s 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 10. -Interferon 11. Others F. Infections 1. Congenital rubella 2. Cytomegalovirus 3. Others

12. 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 associated with diabetes 1. Down’s syndrome 2. Klinefelter’s syndrome 3. Turner’s syndrome 4. Wolfram’s syndrome 5. Friedreich’s ataxia 6. Huntington’s chorea 7. Laurence-moon-Biedl syndrome 8. Myotonic dystrophy 9. Porphyria 10. Prader-Willi syndrome 11. Others IV. Gestational diabetes mellitus ( GDM ) Patients 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.

13. Type 1 DM • Generally <30 years • Rapid onset • Moderate to severe symptoms • Significant weight loss • Lean • Ketonuria or keto-acidosis • Low fasting or post-prandial C-peptide • Immune markers(anti-GAD,ICA,IA-2)

14. 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

15. Pathophysiological model for development of obesity and T2DM Beta-cell defect Glucose toxicity Intra-uterin growth retardation Insulin Resistance + Intraabdominal obesity IGT T2DM Insulin Resistance genes Metabolic Insulin Resistance (FFA) Western lifestyle Obesity genes Year 0 20 40 60 80

16. Disorder of glycemia: etiological types clinical stages Normoglycemia Hyperglycemia Stages Diabetes mellitus Normal glucose tolerance IGT and/or IFG Not insulin requiring Insulin requiring for control Insulin requiring for survival Types Type 1 Type 2 Other specific types Gestational diabetes

17. Acute,life-threatening consequences • Hyperglycemia with ketoacidosis • Nonketotic hyperosmolar syndrome

18. Microvascular complications • Retinopathy • Nephropathy • Peripheral neuropathy • Autonomic neuropathy

19. Macrovascular complications • Atherosclerotic cardiovascular disease • Peripheral vascular disease • cerebrovascular disease

20. Others • Hypertension • Abnormalities of lipoprotein metabolism • Periodontal disease

21. Potential chronic complications of elevated HbA1c • Foot Ulcers • Angina • Heart Attack • Coronary Bypass • Surgery • Stroke • Blindness • Amputation • Dialysis • Kidney Transplant • Albuminuria • Macular Edema • Proliferative Retinopathy • Peridontal Disease • Impotence • Gastroparesis • Depression RISK • Microalbuminuria • Mild Retinopathy • Mild Neuropathy good control poor

22. 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 metabolic disturbance • Prevent or delay the onset of the long-term complications

23. Targets for control

24. Management • Essentials of management • Monitoring of glucose levels • Food planning • Physical activity • Treatment of hyperglycemia

25. 2.Monitoring of Glucose Levels • Blood glucose levels - before each meal - at bedtime • Urine glucose testing • Urine ketone tests (should be performed during illness or when blood glucose is 20mmol/L )

26. 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. • Restrict salt intake to below 7g/d.

27. 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 regularly participate in leisure activities and recreational sports • Do every day adopt healthy lifestyle habits

28. 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, pharmacological therapy should be started without delay.

29. Treatment • Sulphonylureas • Biguanides • -Glucosidase inhibitors • Thiazolidinediones • Glinides • Insulin • Combination therapy

30. 1.Sulphonylureas • Chlorpropamide • Tolbutamide • Glibenclamide • Glipizide • Gliclazide • Gliguidone • Glimepiride

31. 2.Biguanides • Metformin • Phenformin • Buformin

32. 3.-Glucosidase inhibitors • Acarbose • Voglibose • Miglitol

33. 4.Thiazolidinediones • Rosiglitazone • Pioglitazone • Ciglitazone

34. 5.Glinides • Nateglinide • repaglinide

35. 6.Insulin • Insulin is the most efficacious pharmacologic treatment for patients with diabetes

36. 6.Insulin • Indication • Preparation • Therapy • Adverse reaction

37. Management Algorithm for Overweight and Obese T2DM Diet Exercise and weight control Failure Add biguanide, TZD or -glucosidase inhibitors Failure Combine two of these or add sulphonylurea or glinide Failure Check adherance at each step Add insulin or change to insulin

38. Management Algorithm for Non-Obese T2DM Failure Add sulphonylurea, biguanide, -glucosidase inhibitors or glinide Failure Combine sulphonylurea or glinide with biguande and/or -glucosidase inhibitors and/or add TZD Failure Check adherance at each step Add insulin or change to insulin