1. Management of type 2 diabetes in Ramadan fasting Ukandu Igwe Senior Registrar Endocrinology, Diabetes and Metabolism Unit Lagos University Teaching Hospital

3. Outline Introduction Pathophysiology of fasting Risks associated with fasting in diabetes Risk assessment Management Summary

4. Introduction ~1.57 billion Muslims worldwide 23% of world population of 6.86 billion Ramadan is holy month in Islam All healthy Muslims fast

5. Introduction Type 2 DM 6.6% worldwide (20-79 years) 43% of type 1 and 79% of type 2 fast during Ramadan > 50 million with DM fast during Ramadan

6. Introduction In Ramadan, abstain from eating, drinking, use of oral medications, smoking From pre-dawn to after sunset No restriction to food and drink between sunset and dawn Most people take 2 meals

7. Introduction Fasting not meant to add hardship But many insist on it

8. Introduction Pathophysiology of fasting Risks associated with fasting in diabetes Risk assessment Management Summary

9. Pathophysiology of fasting During fasting, blood glucose reduces, causing reduced insulin secretion Catecholamines and glucagon increase, with more glycogenolysis and gluconeogenesis

10. Pathophysiology of fasting With more fasting Depletion of glycogen stores Reduced insulin causes increased free fatty acids (FFA) from adipocytes FFA oxidized to ketones

11. Pathophysiology of fasting Ketones are used as fuel by skeletal muscles, cardiac muscles, adipocytes, kidneys, liver… Glucose spared for erythrocytes and brain Liver glycogen stores (70-80g) last about 12h

12. Pathophysiology of fasting These processes are well coordinated in non- DM individuals But in DM these are perturbed by the underlying pathophysiology and by pharmacological agents

13. Pathophysiology of fasting In type 1, glucagon may fail to rise appropriately in response to dropping glucose Some type 1 also have defective epinephrine secretion (autonomic neuropathy and recurrent hypoglycaemia)

14. Pathophysiology of fasting In severe insulin deficiency, prolonged fasting leads to glycogenolysis, gluconeogenesis and excessive ketogenesis Resultant hyperglycaemia and ketoacidosis

15. Pathophysiology of fasting May have similar findings in type 2 Ketoacidosis uncommon and hyperglycaemia not so severe

16. Introduction Pathophysiology of fasting Risks associated with fasting in diabetes Risk assessment Management Summary

17. Risks associated with fasting in diabetes Hypoglycaemia – more in type 1 Hyperglycaemia Diabetes ketoacidosis (DKA) Dehydration and thrombosis

18. Risks associated with fasting in diabetes Hyperglycaemia Increased incidence x5 of severe hyperglycaemia requiring hospital admission Glycaemic control improves, deteriorates or remains same Hyperglycaemia may be due to excessive reduction of dose to prevent hypoglycaemia Also increased food consumption, especially sugary drinks

19. Risks associated with fasting in diabetes DKA Increased risk, especially if glycaemia is poor Also from excessive reduction in insulin dose on assumption of reduced food intake

20. Risks associated with fasting in diabetes Dehydration, thrombosis Limited fluid Hyperglycaemia also causes osmotic diuresis May have orthostatic hypotension, especially in autonomic neuropathy Contracted intravascular space leads to increased hypercoagulable state, with more risks of thrombosis and stroke

21. Introduction Pathophysiology of fasting Risks associated with fasting in diabetes Risk assessment Management Summary

22. Risk assessment Very high risk Severe hypoglycaemia within 3 months prior to Ramadan History of recurrent hypoglycaemia Hypoglycaemia unawareness Sustained poor glycaemic control DKA within 3 months prior to Ramadan Type 1 DM Acute illness Hyperosmolar hyperglycaemic coma within 3 months prior to Ramadan Performing intense physical labour Pregnancy Chronic dialysis

23. Risk assessment High risk Moderate hyperglycaemia (150-300mg/dl or HbA 1C 7.5-9.0%) Renal insufficiency Advanced macrovascular complications Living alone and treated with insulin or sulphonylurea Pre-morbid conditions that present additional risk factors Old age with ill health Treatment with drugs that may affect mentation

24. Risk assessment Moderate risk Well-controlled DM treated with short-acting insulin secretagogue

25. Risk assessment Low risk Well-controlled DM treated with lifestyle, metformin, acarbose, thiazolodinedione, and/or incretin-based, in otherwise healthy patients

26. Introduction Pathophysiology of fasting Risks associated with fasting in diabetes Risk assessment Management Summary

27. Management Decision to fast personal Careful assessment of risks Medical recommendations most times is ‘don’t fast’ But if patients insist, they should be aware of risks

28. General considerations Individualization: most crucial issue Frequent glycaemic monitoring Nutrition – Avoid large carbohydrates and fats at Iftar – Complex carbohydrates at Suhur and eat as late as possible – Increase water during non-fasting hours Exercise – normal, not excessive. Kneeling and bending

29. Breaking the fast Must break immediately if: – Blood glucose < 60mg/dl – Blood glucose < 70mg/dl in the first few hours, especially if on insulin, sulphonylureas or meglitinides – Blood glucose > 300mg/dl Avoid fasting on sick days

30. Pre-Ramadan medical assessment Should be 1-2 months before fast Diet plan Good control of BP, glucose, lipids

31. Ramadan-focused structured diabetes education Structured education very important in management of DM Opportunity to empower patient, not only about Ramadan But usually lack of harmony between medical and religious advice

32. Ramadan-focused structured diabetes education 3 components Awareness campaign: people living with diabetes, health care professionals, public Ramadan-focused structured education for health care professionals Ramadan-focused structured education for people living with diabetes

33. Ramadan-focused structured diabetes education Health care professionals should be trained to deliver structured patient education Understanding of fasting and DM Risk stratification Options to achieve safer fasting

34. Ramadan-focused structured diabetes education Education delivered Individually or in group sessions DM centres Primary health care centres Mosques… Simple, structured method In patient’s own language

35. Ramadan-focused structured diabetes education Study in the UK, 111 patients At end of Ramadan, those in Ramadan- structured diabetes education had 50% reduction in hypoglycaemia than those without education Also lost small amount of weight

36. Management of type 1 Very high risk Intensive insulin recommended Close monitoring and frequent dose adjustment Basal-bolus best May also use pre-meal rapid acting + once/twice daily intermediate/long-acting Continuous subcutaneous insulin infusion is good but costly

37. Management of type 2 Diet-controlled Low risk Distribute calories over 2-3 smaller meals

38. Management of type 2 Patients on oral antidiabetic Metformin safe, but may modify dosing ( ⅓ : ⅔ ) Glitazones – Low risk of hypoglycaemia – But maximum effects 2-4 weeks, so cannot be quickly substituted

39. Management of type 2 Sulphonylureas – Individualize – Chlorpropamide: relative contraindication – Maybe glibenclamide too – 2 nd generation better – But use with caution

40. Management of type 2 Short-acting insulin secretagogues – Repaglinide and meglitinide twice daily – Lower risk of hypoglycaemia Alpha-glucosidase inhibitors – Usually no effects on fasting blood glucose – So usually used in combination

41. Management of type 2 Incretin-based – Not independently associated with hypoglycaemia – Exenatide can be given before meal. Reduced appetite, weight loss – Liraglutide once daily – DPP4 inhibitors are among best tolerated antidiabetic – Do not require titration

42. Management of type 2 VIRTUE – Vildagliptin experience compared with sulphonylureas observed – >1300 patients – Vildagliptin vs sulphonylureas – Less incidence of hypoglycaemia in vildagliptin VERDI – Vildagliptin experience during Ramadan in patients with diabetes – Multicentre in France – Also lower episodes of hypoglycaemia in vildagliptin – More fasting completion too

43. Management of type 2 Insulin Aim is to maintain basal insulin level Intermediate- or long-acting insulin + short- acting Some will require only basal Analogue said to be better

44. Management of type 2 Insulin pump Provides continuous delivery Patient self-administers bolus with meal or in hyperglycaemia Hypoglycaemia can be prevented by rapid adjustment of dosing Most patients will need to reduce rate of basal and increase bolus doses

45. Recommended changes to treatment regimen in patients with type 2 diabetes who fast during Ramadan Before RamadanDuring Ramadan Patients on diet and exercise control Consider modifying the time and intensity of physical activity; ensure adequate fluid intake Patients on oral hypoglycemic agents Ensure adequate fluid intake Biguanide, metformin 500 mg, three times daily Metformin, 1,000 mg at the sunset meal, 500 mg at the predawn meal TZDs, AGIs, or incretin-based therapies No change needed

46. Recommended changes to treatment regimen in patients with type 2 diabetes who fast during Ramadan Before RamadanDuring Ramadan Sulfonylureas once a dayDose should be given before the sunset meal; adjust the dose based on the glycemic control and the risk of hypoglycemia Sulfonylureas twice a dayUse half the usual morning dose at the predawn meal and the usual dose at sunset meal Patients on insulinEnsure adequate fluid intake Premixed or intermediate-acting insulin twice daily Consider changing to long-acting or intermediate insulin in the evening and short or rapid- acting insulin with meals; take usual dose at sunset meal and half usual dose at predawn

47. Pregnancy Increased risk for mother and fetus If patient insists, intensive care Pre-gestational care, with emphasis on achieving near-normal HbA 1C Appropriate diet and insulin More frequent monitoring and insulin adjustment

48. Hypertension and dyslipidaemia May need to adjust dose of antihypertensives Diuretics may not be OK Continue agents for dyslipidaemia

49. Summary Fasting carries risks Type 1 very high risk Decision to fast should be made after appropriate discussion Those who insist should have pre-Ramadan assessment, education, instructions Some pharmacological agents may cause less hypoglycaemia

50. References Al-Arouj M, Asaad-Khalil S, Buse J, Fahdil I, Fahmy I, Hafez S, et al. Recommendations for management of diabetes during Ramadan. Diabetes Care 2010 (33): 1895-1902 Hui E, Bravis V, Hanif W, Malik R, Chowdhury TA, Suliman M, et al. Management of people with diabetes wanting to fast during Ramadan. BMJ 2010 (340): 1407-11 Halimi S, Levy M, Huet D. Experience with vildagliptin in type 2 diabetic patients fasting during Ramadan in France: Insights from the VERDI Study. Diabetes Ther (2013): 4:385-398

51. References Al-Arouj M, Hassoun AK, Medlej R, Pathan MF, Shaltout I, Chawla MS, et al. The effect of vildagliptin relative to sulphonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: the VIRTUE study. Int J Clin Pract 2013; 67: 933–4.

52. Thank You