1. Slides current until 2008 Diagnosis, classification and prevention of diabetes Section 1 | 1 of 4 Curriculum Module II–1 | Diagnosis, classification and presentation of diabetes

2. Diagnosis and types Curriculum Module II-1 Slide 2 of 48 Slides current until 2008 Definition of diabetes Characterized by hyperglycaemia Defects in insulin production Autoimmune or other destruction of beta cells Insulin insensitivity Impaired action of insulin on target tissues

3. Diagnosis and types Curriculum Module II-1 Slide 3 of 48 Slides current until 2008 Definition of diabetes Chronic hyperglycaemia associated with long-term damage to: Eyes Kidneys Nerves Heart and blood vessels

4. Diagnosis and types Curriculum Module II-1 Slide 4 of 48 Slides current until 2008 The diabetes epidemic 230 million affected in 2006 350 million within 20 years Most rapid in Indian and Asian subcontinents IDF Diabetes Atlas

5. Diagnosis and types Curriculum Module II-1 Slide 5 of 48 Slides current until 2008 Classification Type 1 diabetes –autoimmune –LADA –idiopathic Type 2 diabetes

6. Diagnosis and types Curriculum Module II-1 Slide 6 of 48 Slides current until 2008 Other specific types MODY Defects in insulin action Diseases of the pancreas Endocrine disorders Drug- or chemical-induced Infections Classification

7. Diagnosis and types Curriculum Module II-1 Slide 7 of 48 Slides current until 2008 Uncommon forms of immune- mediated diabetes Other genetic syndromes Gestational diabetes Classification

8. Diagnosis and types Curriculum Module II-1 Slide 8 of 48 Slides current until 2008 Insulin Gluconeogenesis Glycogenolysis Glycogen synthesis Glucose uptake Glycogen synthesis Blood glucose Insulin and glucose disposal Free fatty acid release

9. Diagnosis and types Curriculum Module II-1 Slide 9 of 48 Slides current until 2008 Glucose uptake Glycogenolysis Gluconeogenesis (amino acids) Ketone production (fatty acids) Glucose uptake Protein degradation  amino acids Blood glucose Insulin deficiency in type 1 diabetes Triglyceride degradation  fatty acids

10. Diagnosis and types Curriculum Module II-1 Slide 10 of 48 Slides current until 2008 Glucose uptake Glycolysis Gluconeogenesis (amino acids) Glucose uptake Protein degradation  amino acids Blood glucose Insulin insensitivity in t type 2 diabetes

11. Diagnosis and types Curriculum Module II-1 Slide 11 of 48 Slides current until 2008 Blood glucose Glucose uptake Insensitivity to insulin in t type 2 diabetes Glucose uptake Glycolysis Gluconeogenesis (amino acids) Glucose uptake Protein degradation  amino acids

12. Diagnosis and types Curriculum Module II-1 Slide 12 of 48 Slides current until 2008 Blood glucose Converted to triglycerides Effect of insulin resistance in t type 2 diabetes Glucose uptake Glycolysis Gluconeogenesis (amino acids) Glucose uptake Protein degradation  amino acids Glucose uptake

13. Diagnosis and types Curriculum Module II-1 Slide 13 of 48 Slides current until 2008 Pathogenesis of type 1 diabetes Immunological activation Progressive beta-cell destruction Insufficient beta-cell function Dependent on exogenous insulin Risk of ketoacidosis

14. Diagnosis and types Curriculum Module II-1 Slide 14 of 48 Slides current until 2008 Pathogenesis of type 1 diabetes Genetic susceptibility Immune factors –other autoimmune disease –antigen-specific antibodies Environmental trigger –viruses –bovine serum albumin –nitrosamines: cured meats –chemicals: vacor (rat poison), streptozotin

15. Diagnosis and types Curriculum Module II-1 Slide 15 of 48 Slides current until 2008 Beta-cell mass Pathogenesis of type 1 diabetes Time (months - years) Trigger Genetic Pre-diabetes ‘Honeymoon’ Chronic phase Clinical diabetes Immunological abnormalities

16. Diagnosis and types Curriculum Module II-1 Slide 16 of 48 Slides current until 2008 Idiopathic type 1 diabetes Non-autoimmune type 1 diabetes No autoimmune markers Permanent insulinopenia Ketoacidosis People of African and Asian origin

17. Diagnosis and types Curriculum Module II-1 Slide 17 of 48 Slides current until 2008 Epidemiology of type 1 diabetes Increasing in recent years Geographic variation Relative affluence Lack of treatment IDF Diabetes Atlas

18. Diagnosis and types Curriculum Module II-1 Slide 18 of 48 Slides current until 2008 Age of onset peaks –preschool –puberty Autumn/winter peaks Epidemiology of type 1 diabetes

19. Diagnosis and types Curriculum Module II-1 Slide 19 of 48 Slides current until 2008 Type 2 diabetes 90%-95% of people with diabetes Insulin insensitivity and relative insulin deficiency Obesity or overweight Complications often present at diagnosis

20. Diagnosis and types Curriculum Module II-1 Slide 20 of 48 Slides current until 2008 Pathogenesis of type 2 diabetes Multiple genes involved Hyperinsulinaemia Poor fetal nutrition   beta-cell formation Low birth weight/weight change “Thrifty gene” 7% beta-cell loss

21. Diagnosis and types Curriculum Module II-1 Slide 21 of 48 Slides current until 2008 Age (years) Endogenous insulin Insulin requirements Beta-cell loss The natural history of type 2 diabetes  Insulin requirements with age Primary failure

22. Diagnosis and types Curriculum Module II-1 Slide 22 of 48 Slides current until 2008 Age (years) Endogenous insulin Insulin requirements Beta-cell loss Insulin insensitivity Hyper- insulinaemia The natural history of type 2 diabetes  Insulin requirements with age

23. Diagnosis and types Curriculum Module II-1 Slide 23 of 48 Slides current until 2008 Age (years) Endogenous insulin Insulin requirements Secondary failure The natural history of type 2 diabetes Effect of oral drugs  Insulin requirements with age Beta-cell loss Hyper- insulinaemia Insulin insensitivity

24. Diagnosis and types Curriculum Module II-1 Slide 24 of 48 Slides current until 2008 Epidemiology of type 2 diabetes Dramatic increase Aging population Disturbing trends parallel obesity epidemic Especially in adolescents and minority groups Increasing in young people

25. Diagnosis and types Curriculum Module II-1 Slide 25 of 48 ACTIVITY Slides current until 2008 What are the most common risk factors for type 2 diabetes for people in your country? Are any of these risk factors modifiable?

26. Diagnosis and types Curriculum Module II-1 Slide 26 of 48 Slides current until 2008 Risk factors for type 2 diabetes Age > 40 years First-degree relative with diabetes Member of high risk population History of impaired glucose tolerance, impaired fasting glucose Vascular disease History of gestational diabetes History of delivery of macrosomic baby CDA 2003

27. Diagnosis and types Curriculum Module II-1 Slide 27 of 48 Slides current until 2008 Hypertension Dyslipidaemia Abdominal obesity Overweight Polycystic ovary disease Acanthosis nigricans Schizophrenia Risk factors for type 2 diabetes

28. Diagnosis and types Curriculum Module II-1 Slide 28 of 48 Slides current until 2008 Polydipsia Polyuria Nocturia Visual disturbance Fatigue Weight loss Infections Signs and symptoms

29. Diagnosis and types Curriculum Module II-1 Slide 29 of 48 Slides current until 2008 Diagnosing diabetes NormalImpaired fasting glucose* Impaired glucose tolerance** Diabetes FPG <6.1mmol/L <110mg/dL 6.1 to 6.9mmol/L* 110 to 126mg/dL ≥7.0mmol/L ≥126mg/dL 2hr PG <7.8mmol/L <126mg/dL 7.8 to 11mmol/L** 126 to 200mg/dL ≥11.1mmol/L ≥200mg/dL CDA 2003, ADA 2004, WHO 2002

30. Diagnosis and types Curriculum Module II-1 Slide 30 of 48 Slides current until 2008 Impaired glucose tolerance Impaired fasting glucose Intermediate states Increased risk of developing diabetes Prevention strategies to prevent or delay progression Increased risk of cardiovascular disease

31. Diagnosis and types Curriculum Module II-1 Slide 31 of 48 Slides current until 2008 Uncertain diagnosis: Oral glucose tolerance test 75 g glucose load after 8 hours fasting Readings taken in fasting state and at 1 and 2 hours Possible problems

32. Diagnosis and types Curriculum Module II-1 Slide 32 of 48 Slides current until 2008 Urinary ketones Antibodies C-peptide Tests for differential diagnosis

33. Diagnosis and types Curriculum Module II-1 Slide 33 of 48 Slides current until 2008 Metabolic syndrome Cluster of risk factors or syndrome Type 2 diabetes Different criteria Three-fold increase in heart disease and stroke Two-fold increase in cardiovascular disease deaths

34. Diagnosis and types Curriculum Module II-1 Slide 34 of 48 Slides current until 2008 Prevention of type 1 diabetes Early exposure to cows milk protein Nicotinamide

35. Diagnosis and types Curriculum Module II-1 Slide 35 of 48 Slides current until 2008 Prevention of type 1 diabetes Insulin Diabetes Prevention Trial Diabetes Prediction and Prevention Project

36. Diagnosis and types Curriculum Module II-1 Slide 36 of 48 Slides current until 2008 Prevention of type 2 diabetes Lifestyle modification Da Qing Study Finnish Diabetes Prevention Study

37. Diagnosis and types Curriculum Module II-1 Slide 37 of 48 Slides current until 2008 Prevention of type 2 diabetes Lifestyle vs medication Diabetes Prevention Program STOP-NIDDM

38. Diagnosis and types Curriculum Module II-1 Slide 38 of 48 ACTIVITY Slides current until 2008 Type 2 diabetes can be delayed in people with IGT Lifestyle modification is most effective What do you think could be done at community level to prevent or delay diabetes?

39. Diagnosis and types Curriculum Module II-1 Slide 39 of 48 Slides current until 2008 Summary Type 1 diabetes Results from progressive beta- cell destruction People with type 1 diabetes need insulin therapy to live

40. Diagnosis and types Curriculum Module II-1 Slide 40 of 48 Slides current until 2008 Type 2 diabetes Often characterized by insulin insensitivity and relative rather than absolute insulin deficiency A progressive condition Most people with type 2 diabetes will need insulin within 5 to 10 years of diagnosis Summary

41. Diagnosis and types Curriculum Module II-1 Slide 41 of 48 Slides current until 2008 Review question 1. The pathogenesis for type 2 diabetes includes: a. Insulin deficiency and insulin insensitivity b. Insensitivity to insulin and autoimmune beta-cell destruction c. Autoimmune beta-cell destruction and glucagon deficiency d. Insulin deficiency and glucagon deficiency

42. Diagnosis and types Curriculum Module II-1 Slide 42 of 48 Slides current until 2008 Review question 2. A person with type 2 diabetes, recently started on insulin, asks if there is a way to measure if he/she is still producing any insulin. The correct response would be: a. Islet cell antibody tests b. C-peptide test c. HbA 1c test d. Serum insulin test

43. Diagnosis and types Curriculum Module II-1 Slide 43 of 48 Slides current until 2008 Review question 3. The Diabetes Prevention Program (DPP): a. Included people with type 1 diabetes b. Included only people with IGT c. Tested the value of exercise d. Included people with type 2 diabetes

44. Diagnosis and types Curriculum Module II-1 Slide 44 of 48 Slides current until 2008 Review question 4. Type 1 diabetes is usually caused by: a. Injury to the pancreas b. An autoimmune reaction c. Insulin insensitivity in the cells d. Hypersensitivity to insulin

45. Diagnosis and types Curriculum Module II-1 Slide 45 of 48 Slides current until 2008 Answers 1.a 2.b 3.b 4.b

46. Diagnosis and types Curriculum Module II-1 Slide 46 of 48 Slides current until 2008 References 1.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004; 27(suppl 1): S5-S10. 2.Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diab 2003; 27(suppl 2). 3.Chiasson JL, Josse RG, Gomis R, et al. Acarbose for prevention of type 2 diabetes mellitus: The STOP-NIDDM randomized trial. Lancet 2002; 346: 393-403. 4.Delahanty LM and Halford BN. The role of Diet Behaviours in Achieving improved glycaemic control in intensively treated patients in the Diabetes Control and Complications Trial. Diabetes Care 1993; 16(11): 1453-58. 5.Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin dependent diabetes mellitus: Diabetes Control and Complications Trial. The Journal of Paediatrics 1994; 125(2): 177-88. 6.Diabetes Control and Complications Trial/epidemiology of diabetes interventions and complications research group intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. New Engl J Med 2003; 348: 2294-303. 7.Diabetes Control and Complications Trial: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-86.

47. Diagnosis and types Curriculum Module II-1 Slide 47 of 48 Slides current until 2008 References 8.Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 297: 356-59. 9.Diabetes Atlas 2006. Brussels: International Diabetes Federation, 2006. 10.Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24(4): 683-9. 11.Pan X, Li G, Hu Y, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20(4): 537-44. 12.Report of a WHO Consultation. Laboratory Diagnosis and monitoring of Diabetes Mellitus. World Health Organisation 2002. http://whqlibdoc.who.int/hq/2002/9241590483.pdf cited April 30, 2005.http://whqlibdoc.who.int/hq/2002/9241590483.pdf 13.Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Eng J Med 2001; 344: 1343-50. 14.The Diabetes Prevention Program Research Group. The diabetes prevention Program (DPP). Diabetes Care 2002; 23(12): 2165-71. 15.UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulpfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998; 352: 837-53.

48. Diagnosis and types Curriculum Module II-1 Slide 48 of 48 Slides current until 2008 References 16.UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes UKPDS 38. BMJ 1998; 317: 703-13. 17.IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes. Brussels: International Diabetes Federation, 2005. 18.Harris SB, Ekoe JM, Zdanowicz Y, Webster-Bogaert S. Glycemic Control and morbidity in the Canadian primary care setting (results of the diabetes in Canada evaluation study). Diab Research and Clin Pract 2005; 70: 90-7.