2. DIABETES MELLITUS Dr Mohammed Saeed

3. definition diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.

4. Presenting symptoms thirst, polyuria, blurring of vision, and weight loss. In its most severe forms, ketoacidosis or a non–ketotic hyperosmolar state may develop and lead to stupor, coma and, in absence of effective treatment, death. Often symptoms are not severe, or may be absent altogether

5. criteria for diagnosing diabetes mellitus: symptomatic Diabetes symptoms (ie polyuria, polydipsia and unexplained weight loss) plus  a random venous plasma glucose  11.1 mmol/ or  a fasting plasma glucose  7.0 mmol/l or  2 hour plasma glucose  11.1 mmol/l 2 hours after 75g anhydrous glucose in OGTT

6. criteria for diagnosing diabetes mellitus: asymptomatic At least one additional laboratory plasma glucose on another day with a value in the diabetic range is essential –either fasting –from a random sample –or from the two hour post glucose load If the fasting or random values are not diagnostic the 2-hour value should be used WHO web site and Diabetes UK web site

7. Glucose Liver Peripheral Tissues (Muscle) Pancreas Receptor + postreceptor defect Increased glucose production Impaired insulin secretion Insulin resistance P.6 Causes of Hyperglycemia in Type 2 Diabetes © 1997 PPS C

8. Physiologic Serum Insulin Secretion Profile Polonsky KS et al, N Engl J Med 1996. 75 50 25 0 Plasma Insulin (  U/mL) Plasma Insulin (  U/mL) Time 4:008:0012:0016:0020:0024:0028:0032:00 Breakfast Lunch Dinner

9. 26 million with Diabetes 79 million with Pre-Diabetes

10. Epidemic of Diabetes Diabetes affects almost 26 million Americans (8.3%), one quarter of whom don’t know they have it. Another 79 million Americans have pre-diabetes, which raises their risk of developing type 2 diabetes, heart disease, and stroke. About 1.9 million new cases of diabetes were diagnosed in people aged 20 or older in 2010. www.yourdiabetesinfo.orgwww.DiabetesAtWork.org

11. Source: 2005–2008 National Health and Nutrition Examination Survey.

12. The Diabetes Epidemic Aging of America Diverse ethnic groups, various incidence and prevalence of diabetes Earlier diagnosis and reclassification Pre-diabetes: “Borderline Diabetes” or a “touch of sugar” = real condition that needs to be treated By 2050, 1 in every 3 adult Americans will have diabetes if current trends continue

13. Diabetes 101: What is Diabetes Not just a “sugar” problem Interaction of food, insulin, other hormones (glucagon) Physical activity/Obesity Pancreatic function Genetics Other commonly associated conditions: hypertension, lipid problems The complications, not just the diagnosis of diabetes, cause the problems Diabetes is common, serious BUT treatable

14. Diabetes means: 2 x the risk of high blood pressure 2 to 4 x the risk of heart disease 2 to 4 x the risk of stroke #1 cause of adult blindness #1 cause of kidney failure Causes more than 60% of non-traumatic lower-limb amputations each year NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2010.

15. Complications Eyes Kidneys Nerves Cardiovascular disease and stroke Randomly controlled studies show that these complications can be prevented or controlled with good blood sugar control but this might involve multiple shots etc More shots does not mean “worse diabetes”!

16. Symptoms Frequent urination Excessive thirst Extreme hunger or constant eating Unexplained weight loss Presence of glucose in the urine Tiredness or fatigue Changes in vision Numbness or tingling in the extremities Slow-healing wounds or sores Abnormally high frequency of infection Many people have no symptoms

17. Diagnosis (Diabetes Care 1-2010) 1) A1C ≥6.5%. (by lab using a method that is NGSP certified and standardized to the DCCT assay.* (caveats: anemia, pregnancy) OR 2) FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.* OR 3) 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR 4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l). *In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing

18. Types of Diabetes Type 1: traditionally age <20, no endogenous insulin, may be any age, about10-20% of people with diabetes, Rx = insulin Type 2: traditionally >40, multiple problems with insulin secretion and action, may be any age, about 80-90% of people with diabetes, Rx may include oral agents and/or insulin or newer agents (incretins, GLP1 ) Pre-diabetes Gestational Diabetes

19. Who Is At Risk? Age 45 or older Overweight Inactive Ethnic or minority population Family history of diabetes Excess abdominal fat High blood pressure Pre-diabetes High blood fats Darkening of the skin Polycystic ovary syndrome History of Gestational Diabetes or large baby

20. Categories of increased risk for diabetes (Pre-diabetes) Impaired Fasting Glucose: FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l) Impaired Glucose Tolerance: 2-h PG in the 75-g OGTT : 140 mg/dl (7.8 mmol/l) - 199 mg/dl (11.0 mmol/l) A1C 5.7–6.4% For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range.

21. Pathological processes Type 1 pancreatic islet beta–cell destruction prone to ketoacidosis autoimmune and idiopathic Type 2 common results from defect(s) in insulin secretion almost always with a major contribution from insulin resistance

22. Clinical staging (applies to all types of pathological processes) Normal glucose tolerance Impaired Glucose tolerance Diet controlled diabetes (Oral hypoglycaemic drugs needed for glycaemic control) Insulin needed for glycaemic control Insulin needed for life*

23. Type 2 diabetes natural history B cell function 100% 25% 10% Increasing hyperglycaemia mmol/l 710 Insulin needed

24. Type 1 Autoantibodies present for several years (islet cell, GAD, insulin 80-90%) Family history (about 10%) HLA phenotype DR3 & 4 Environment Any age, any weight

25. Presumed sequence Viral infection in utero White cell or islets affected Further viral infection Autoimmune process started Cell immune kill Type 1 Diabetes presents with season flu

26. Type 2 diabetes - associations the metabolic syndrome Hypertension (c50%) Hyperlipidaemia Large waist Overweight and genetic causes of this microalbuminuria cardiovascular disease insulin resistance

27. Abdominal obesity increases the risk of developing type 2 diabetes <7171–75.976–8181.1–8686.1–9191.1–96.3>96.3 24 20 16 12 8 4 0 Relative risk Waist circumference (cm) Carey et al 1997

28. Type 2 diabetes: suggested causes Thrifty genotype –diabetes if plenty of food –resistant to starvation if famine Thrifty phenotype Results from neonatal undernutrition babies light for dates –diabetes results if plenty of food –resistant to starvation if famine

29. Low birth weight may cause type 2 diabetes

30. Other causes of type 2 diabetes Overweight –increases insulin resistance Decreased exercise –increases insulin resistance

31. Type 2 diabetes can be prevented! Exercise Weight reduction 5 portions of fruits and vegetables Increase of mono- less poly-un & saturated fats Reduces risk by 70%

32. After all that The person with diabetes presents and needs insulin how do you persuade someone to start something that is perceived as painful?

41. What are the complications of diabetes? acutechronic

42. Some examples

43. Acute complications of diabetes Metabolic Ketoacidosis or hyperosmolar hypoglycaemia Social - often chronic food & hospitality activity jobs alcohol driving & travel

44. Before insulin

45. after insulin therapy, and food!

46. Man with type 1 diabetes 1 day after admission, unable to sit up because of loss of muscle bulk he had been treated with diet and metformin

47. Chronic complications of diabetes Microvascular retinopathy nephropathy neuropathy- –peripheral –autonomic –impotence Macrovascular myocardial infarction stroke peripheral vascular disease – amputation

48. Normal retina

49. Background retinopathy: microaneurysms and exudates Exudates microaneurysm

50. Gross changes from photocoagulation as well as central vein occlusion

51. Large abscess

52. Congenital abnormalities are commoner in women with diabetes if HbA1c raised at conception

53. Foot subsequently healed – and stayed on !

54. Without revascularisation above knee amputation needed

55. complications can be prevented

56. Glycaemic control is at the moment measured by HbA1c

57. HbA1 c and macro and microvascular complications

58. Incidence of any diabetes endpoint by systolic BP

59. Prevalence of diabetes type 1 0-15: 0.1% (Leicester) over 15: 0.4% type 2 0-15 about 0% 40-80: 70%

60. Treatment of type 2 diabetes Initial steps Increased exercise Diet –small frequent meals low in refined sugar –hypocaloric if overweight measure effect with HbA1c and patient monitoring

61. Stepped treatment of type 2 diabetes when HbA1c above normal If overweight metformin up to 1.5G  insulin secretagogue  glitazone  insulin New problems: does rosiglitazone kill? New treatments: exanatide and ddpiv inhibitors: GLP1 action; decrease glucagon change gastric emptying, reduce food input centrally Do they reduce CHD deaths? Not overweight insulin secretagogue  glitazone  insulin

62. Surveillance for complications Urine for albuminuria Eye examination annually –with retinal camera Foot examination of pulses Foot examination of sensation –vibrameter –weighted fibre

63. Why Control Diabetes? Do Any Interventions Work? Bottom Line: Does better glucose control translate to better outcomes or better health in the individual? Yes! For every 1% drop in A1c the risk of microvascular complications (eye, kidney, and nerve damage) can be reduced by up to 40%. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.p

64. Control the ABCS A1c: Glucose control Blood Pressure control Cholesterol (lipid) control Smoking cessation

65. Thank you for listening!