1. Diabetes Mellitus Year 1 Michaelmas term

2. Diabetes Mellitus ● Diabetes: Latin from Greek “Excess flow of urine” ● Mellitus Latin “like honey”

3. Case 1

4. ● A 23 year-old man is admitted to hospital with 3 week history of: ● Severe thirst (polydipsia) ● Excessive urine production (polyuria) ● Weight loss 12 kg He is previously fit and rows in a local team

5. investigations ● Urine tests positive for glucose and ketones ● Blood glucose 45mmol/l (normal 3-7mmol/l) ● Arterial pH 7.1 (normal 7.4)

6. Why is the blood glucose elevated?

7. hyperglycaemia ● Due to lack of insulin ● As a consequence glucose uptake into cells is reduced ● In type 1 diabetes this is due to immune- mediated destruction of the beta cells in the islets of Langerhans ● Type 1 diabetics have low levels of insulin

8. Why is the arterial sample acidotic?

9. acidosis ● Glucose cannot get into the cells due to lack of insulin ● Alternative fuel sources used, resulting in proteolysis and lipolysis ● Ketone bodies are produced from lipolysis ● These are acidotic and are a cause of metabolic acidosis

10. Why has he lost weight?

11. Weight loss ● Due to protein and fat catabolism ● Produces metabolites from gluconeogenesis and lipolysis ● Weight loss also occurs due to dehydration

12. What causes the thirst and polyuria?

13. Thirst and polyuria ● Glucose leaks from the kidney as the usual reabsorption mechanism is overwhelmed ● Glucose excretion causes an osmotic diuresis, as water is lost with the glucose. This increases urine production ● This causes dehydration ● Dehydration causes thirst

14. How would you treat the patient?

15. treatment ● Rehydration IV ● IV insulin pump ● Commence diabetic diet ● Convert to twice daily sub-cutaneous insulin ● Teach self-monitoring of blood glucose using finger-prick and Glucometer

16. The patient is stabilised on insulin, but wants to resume rowing How would you advise him?

17. When taking exercise…. ● May need to reduce insulin requirements ● Check your blood glucose before exercise ● Watch out and be prepared for a “hypo”

18. What is a diabetic “hypo”?

19. A diabetic “hypo” ● Hypoglycaemia occurs when blood glucose <3.0mmol/l ● Initially get autonomic warning signs: tremor, sweating, palpitations ● If ignored may may develop neuroglypenia (reduced glucose supply to brain), causing behavioral changes, confusion and fits ● If untreated may develop coma

20. Treatment of a “hypo” ● If patient can recognise symptoms early then correct blood glucose with biscuits or sweet drink ● If patient confused may treat with Glucogel ● If unconscious give 10%IV glucose and/or glucagon IM/IV

21. Case 2

22. ● A 60 year old Opera singer who is substantially overweight goes to see her doctor for a check-up as she has been feeling a bit tired recently. ● She is found to have a BMI of 33 ● Her blood pressure is elevated 160/100 ● The foot pulses are not palpable ● There is protein in the urine on testing ● A random blood glucose was 14 mmol/l

23. What type of diabetes does this lady have, and why?

24. Type 2 diabetes ● Type 2 DM most likely in view of : ● Age >40 in white Europeans ● High BMI ● Few symptoms: Type 2 may have mild polydipsia/polyyuria/tiredness/itching/poor wound healing ● (Type 1 tends to present as children or young adults with a short history of severe symptoms)

25. Body Mass Index BMI ● Weight Kg/height m 2 ● A BMI less than 18.5 is underweight ● A BMI of 18.5 - 24.9 is normal weight ● A BMI of 25.0 - 29.9 is overweight ● A BMI of 30.0 - 39.9 is obese ● A BMI of 40.0 or higher is severely (or morbidly) obese

26. Type 2 diabetes ● Is also the most common type of diabetes in the UK: 85-90% all cases ● Around 2 million cases in UK ● Up to 750,000 other cases undiagnosed

27. How would you confirm she has diabetes? ● Fasting blood glucose >7.0mmol/l ● Random blood glucose >11mmol/l ● If in doubt could do glucose tolerance test ● Check fasting level (normal < 7.0mmol/l) ● Give 75g glucose drink ● Test 2h blood glucose (normal <8.0mmol/l) ● 8-11 mmol/l= impaired glucose tolerance ● >11.1 diabetes

28. How does blood glucose rise in type 2 diabetes?

29. Hyperglycaemia in type 2 diabetes ● Initial phase of insulin resistance ● Serum insulin levels normal or elevated, due to post-receptor defect ● Eventually beta cells begin to fail and pateint develops insulin deficiency ● Oral hypoglycemics and diet alone less likely to be effective ● Need to transfer to insulin in later stages

30. How would you treat this lady? ● Start diabetic diet (low fat, normal protein, unrefined CHO) ● If no improvement after a few weeks start an oral hypoglycemic: Metformin drug of choice (UK Prospective Diabetes Study). Metformin reduces insulin resistance: reduces hepatic glucose output; increases glucose uptake in muscle ● May subsequently require addition of sulphonylurea (stimulates I production) or glitazone (stimulates nuclear receptors in adipose tissue, reducing insulin resistance)

32. Why is there protein in the urine?

33. proteinuria ● The patient may have had undiagnosed diabetes for some years and developed microvascular complications ● She may have diabetic renal glomerular damage ● Alternatively she may have renal damage from hypertension causing a hypertensive nephropathy ● The drug of choice for diabetic or hypertensive nephropathy is an ACE inhibitor or an angiotensin receptor blocker

34. Microvascular complications: ● Nephropathy (test for proteinuria) ● Retinopathy (examine retina) ● Neuropathy e.g numbness of feet

35. Why are her foot pulses absent?

36. Absent foot pulses ● Peripheral vascular disease. This may develop in type 1 and type 2 diabetes ● Also associated with hypertension and smoking and dyslipidaemia ● 3 main large vessel complications: peripheral vascualr disease, stroke and heart attacks ● Main cause of death in type 1 and type 2 diabetes

37. What are this lady’s chances of living to 70, and why?

38. prognosis ● She is unlikely to live to 70 because there is evidence of both macrovascular and microvascualr complicatins ● If she has atheroma in the peripheral circulation it is likely it is also present in the coronary and cerebral arteries ● High risk of heart attack or stroke

39. Any other treatment to improve prognosis?

40. Other treatment ● Give ACE inhibitor to protect kidneys ● Give statin to lower cholesterol levels ● Give aspirin to reduce platelet stickiness and reduce cardiovascular risk ● Encourage to lose weight

41. Are YOU at risk of getting diabetes? ● The “measure-up” test: ● http://www.diabetes.org.uk/ http://www.diabetes.org.uk/ ● Includes age/gender/FH/ethnic origin/waistline/BMI/history of gestational DM/big babies/history of MI etc

42. And finally…. What do you make of these graphs from ● David Haslam, Naveed Sattar, and Mike Lean Obesity—time to wake up BMJ, Sep 2006; 333: 640 - 642 ; doi:10.1136/bmj.333.7569.640 ● Obesity may bankrupt health services BMJ, Sep 2006; 333: 0 ; doi:10.1136/bmj.333.7569.0-b

43. Copyright ©2006 BMJ Publishing Group Ltd. Haslam, D. et al. BMJ 2006;333:640-642 Prevalence of obesity worldwide. Adapted from Haslam D, James WP. Lancet 2005;366: 1197-209

44. Copyright ©2006 BMJ Publishing Group Ltd. Haslam, D. et al. BMJ 2006;333:640-642 Results from Health Survey for England 2002. The most recent Health Survey for England (2004) states that "Between 1995 and 2001, mean BMI increased among boys (from 17.6 to 18.1) and girls (from 18.0 to 18.4) aged 2-15"