Practical Guide Diabetes and Ramadhan.pptx

Diabetes Ramadan

1. Practical Guide to Diabetes Management in Ramadan

2. Contents 2 Background Pathophysiology of fasting during Ramadan Medical benefits of fasting during Ramadan Risks of fasting in diabetes during Ramadan Patients who are at risk of developing complications during fasting Preparation prior to Ramadan Self-monitoring of blood glucose (SMBG) during Ramadan Lifestyle and diet management during Ramadan Oral anti-diabetic therapy during Ramadan Insulin therapy during Ramadan

3. BACKGROUND 3

4. Background Fasting with diabetes Associated with adverse outcomes 1,2 Dehydration Hypoglycaemia Hyperglycaemia Hence, not obliged to fast 1,2 Patients choose to fast EPIDIAR study showed 42.8% of patients with Type 1 and 78.7% with Type 2 diabetes mellitus fasting at least 15 days during Ramadan 3 High risk of developing hypoglycaemia 4 Healthcare professionals Pre-fasting education and planning 2 To lower incidence of adverse outcomes 2 4 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med . 2010; 103(4): 139-147. Salti I, Bénard E, Detournay B, et al. A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care . 2004; 27(10): 2306-2311. Loke SC, Rahim KF, Kanesvaran R, et al. A prospective cohort study on the effect of various risk factors on hypoglycaemia in diabetics who fast during Ramadan. Med J Malaysia . 2010; 65(1): 3-6.

5. PATHOPHYSIOLOGY OF FASTING DURING RAMADAN 5

6. Physiology of Fasting during Ramadan 6 Liver Peripheral tissues (muscle) Gluconeogenesis Increased glucose uptake Glycogen stores depleted Insulin secretion decreased Glucose Pancreas References: Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med . 2010; 103(4): 139-147. In normal healthy individuals, eating stimulates the secretion of insulin from the islet cells of the pancreas. This in turn results in glycogenesis and storage of glucose as glycogen in liver and muscle. During fasting secretion of insulin is reduced while counter-regulatory hormones glucagon and catecholamines are increased. This leads to glycogenolysis and gluconeogenesis. The low levels of insulin in circulation also lead to increased fatty acid release and oxidation that generates ketones which are used for nutrition by the body. Adapted from Figure 1 Pathophysiology of fasting in normal individuals : Karamat et al.

7. Pathophysiology of Fasting in Diabetics during Ramadan 7 References: Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010. Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med . 2010; 103(4): 139-147. In the normal fed state, glycogen is the body’s main source of energy. Secretion of insulin is reduced while counter-regulatory hormones glucagon and catecholamines are increased. During a fast, these glycogen stores are utilised first to produce energy. The liver glycogen is depleted in the first 18 to 24 hours via glycogenolysis. Later in the fasting state, once glycogen stores are depleted, fat becomes the next source of energy for the body. Fats are mobilised in the form of triglycerides which further undergo lipolysis into free fatty acids and glycerol. With prolonged periods of fasting (days to weeks), protein becomes the source of energy and will be released from the catabolism of muscle. Glucose Liver Peripheral tissues (muscle) Gluconeogenesis & ketogenesis Increased glucose uptake Glycogen stores depleted Excessive breakdown Insulin secretion decreased or absent Adapted from Figure 2 Pathophysiology of fasting in diabetes : Karamat et al. Pancreas Type 1 diabetes In patients with Type 1 diabetes, glucose homeostasis is affected by underlying disease and by insulin therapy. Glucagon secretion may fail to increase appropriately in response to hypoglycaemia, and in patients with severe insulin deficiency, a prolonged fast in the absence of adequate basal insulin can lead to excessive glycogen breakdown and increased gluconeogenesis and ketogenesis leading to hyperglycaemia and eventual ketoacidosis. Type 2 diabetes Patients with Type 2 diabetes may suffer similar consequences, however ketoacidosis is uncommon.

8. MEDICAL BENEFITS OF FASTING DURING RAMADAN 8

9. Medical Benefits of Fasting during Ramadan Reduction in body mass index (BMI) Decrease in body weight 1 With or without any changes in total cholesterol and triglycerides levels Increase in high-density lipoprotein (HDL) 2 Improvement of HbA1c level Improvement in glycaemic control 3 Decrease in daytime average systolic and diastolic blood pressures in hypertensive patients Decrease in blood pressure 4,5 9 References: Mafauzy M, Mohammed WB, Anum MY, et al. A study of the fasting diabetic patients during the month of Ramadan. Med J Malaysia . 1990; 45(1): 14-17. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract. 2006; 73(2): 117-125. Chamakhi S, Ftouhi B, Rahmoune NB, et al. Influence of the fast of Ramadan on the balance glycaemic to diabetics. Medicographia . 1991; 13: 27-29. Perk G, Ghanem J, Aamar S, et al. The effect of the fast of Ramadan on ambulatory blood pressure in treated hypertensives. J Hum Hypertens . 2001; 15(10): 723-725. Akturk IF, Biyik I, Kocas C, et al. PP-014 The effect of Ramadan fasting on blood pressure levels of hypertensive patients with combination therapy. Int J Cardiol . 2012; 155(Suppl 1): S103. Cheng CW, Adams GB, Perin L, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014; 14(6): 810-823. Ibrahim O, Kamaruddin N, Wahab N, et al. Ramadan Fasting And Cardiac Biomarkers In Patients With Multiple Cardiovascular Disease Risk Factors. The Internet Journal of Cardiovascular Research. 2010; 7(2). Reduction in high sensitive C-reactive protein (hs-CRP) Reduction in plasminogen activator inhibitor type-1 (PAI-1) Reduced cardiovascular disease markers 7 Elimination of toxins Reducing insulin-like growth factor 1 (IGF-1) which allows the regeneration of stem cells in the bone marrow Improvement in immunity 6

10. Changes in Average SBP and DBP for Hypertensive Patients 10 Abbreviation: BP: Blood pressure; SBP: Systolic blood pressure; DBP: Diastolic blood pressure Reference: Akturk IF, Biyik I, Kocas C, et al. PP-014 The effect of Ramadan fasting on blood pressure levels of hypertensive patients with combination therapy. Int J Cardiol . 2012; 155(Suppl 1): S103. Average 24-h Average awake Average asleep Ramadan fasting in Islamic populations of the world may cause significant reductions on daytime and twenty four hour average systolic and diastolic blood pressures in hypertensive patients with combination therapy.

11. Decrease in Body Weight 11 Reference: Mafauzy M, Mohammed WB, Anum MY, et al. A study of the fasting diabetic patients during the month of Ramadan. Med J Malaysia . 1990; 45(1): 14-17. 0.7 kg decrease of mean body weight It was observed that the body weight decreased from 60.5 ± 12.6 kg before Ramadan to 59.8 ± 12.3 kg with a mean decrease in of 0.7 ± 1.3 kg, p=0.01.

12. Improve in Glycaemic Control 12 The significant fall in the serum fructosamine level implied that the overall glycaemic control was significantly better during the fasting month than before. 2.3 mmol/l decrease of mean body weight Before Ramadan During Ramadan Reference: Mafauzy M, Mohammed WB, Anum MY, et al. A study of the fasting diabetic patients during the month of Ramadan. Med J Malaysia . 1990; 45(1): 14-17.

13. Changes in Total Cholesterol and Triglycerides Levels 13 The total cholesterol and triglycerides was maintained until post-Ramadan. For diabetic patients apo A-1/HDL ratios level increased after Ramadan and this parameter as determined from this study, would suggest a reduced CHD risk with Ramadan fasting. Pre-Ramadan Post-Ramadan HDL (mM) Apo A-1/HDL ratio Total cholesterol (mM) Triglycerides (mM) Reference: Akanji AO, Mojiminiyi OA, Abdella N. Beneficial changes in serum apo A-1 and its ratio to apo B and HDL in stable hyperlipidaemic subjects after Ramadan fasting in Kuwait. Eur J Clin Nutr . 2000; 54: 508-513. CHD: Coronary heart disease HDL: High density lipoprotein

14. RISKS OF FASTING IN DIABETES DURING RAMADAN 14

15. Risks of Fasting during Ramadan Hypoglycaemia Increase in hospitalisation due to hypoglycaemia 1 Diabetics with HbA1c <8% and the elderly have more than twice the risk of developing hypoglycaemia during the fasting month 2 Hyperglycaemia/ ketoacidosis Increase in hospitalisation due to hyperglycaemia 1 Patients who are poorly controlled before Ramadan are at an increased risk of diabetic ketoacidosis (DKA) 3 Dehydration Occurs due to limitation in fluid intake (prolonged fasting and those who perform hard and physical labour) 3 Orthostatic hypotension may occur leading to syncope, falls, injuries and fractures 3 Hypercoagulable state in diabetes might be exacerbated, enhancing the risk of thrombosis and stroke 3 15 References: Salti I, Bénard E, Detournay B, et al A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care . 2004; 27(10): 2306-2311. Loke SC, Rahim KF, Kanesvaran R, et al. A prospective cohort study on the effect of various risk factors on hypoglycaemia in diabetics who fast during Ramadan. Med J Malaysia . 2010; 65(1): 3-6. Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010.

16. Risk of Hypoglycaemia during Ramadan 16 Type 1 diabetes Type 1 diabetes Type 2 diabetes Type 2 diabetes Overall population Patient who fasted ≥15 days P = 0.0174 P < 0.0001 P = 0.9896 P = 0.0034 Before Ramadan During Ramadan Among the overall population, the number of severe hypoglycaemic episodes per month and per patient was significantly higher during Ramadan than during the preceding year for patients with Type 1 diabetes as well as for patients with Type 2 diabetes. Among patients who fasted for at least 15 days, the frequency of severe hypoglycaemia complications was slightly lower than in the overall population. For these patients, significant differences were reported in frequency of severe hypoglycaemia complications per patient per month between Ramadan and the preceding year for patients with Type 2 diabetes but not Type 1 diabetes. Reference: Salti I, Bénard E, Detournay B, et al A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care . 2004; 27(10): 2306-2311. .

17. Risk of Hyperglycaemia/Ketoacidosis during Ramadan 17 Type 1 diabetes Type 1 diabetes Type 2 diabetes Type 2 diabetes Overall population Patient who fasted ≥15 days P = 0.1635 P < 0.0001 P = 0.6701 P = 0.0015 Before Ramadan During Ramadan Among the overall population, the number of severe hyperglycaemic episodes with or without ketoacidosis per month showed a significant difference between Ramadan and the preceding year only for patients with Type 2 diabetes. Among patients who fasted for at least 15 days, the frequency of severe hyperglycaemia complications was slightly lower than in the overall population. Type 2 diabetes reported higher severe complications per month than Type 1 diabetes. Reference: Salti I, Bénard E, Detournay B, et al A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care . 2004; 27(10): 2306-2311. .

18. PATIENTS WHO ARE AT RISK OF DEVELOPING COMPLICATIONS DURING FASTING 18

19. Patients Who Are at Risk of Developing Complications during Fasting Categories of risk in patients with Type 1 or Type 2 diabetes mellitus who fast during Ramadan 1 a) Very high risk* Severe complications within 3 months prior to fasting Severe hypoglycaemia Ketoacidosis Hyperosmolar hyperglycaemic coma Recurrent hypoglycaemia Hypoglycaemia unawareness Acute illness Sustained poor glycaemic control (HbA 1c >9%) Pregnancy Advanced renal failure / Chronic dialysis b) High risk* Moderate hyperglycaemia (HbA1c 7.5–9.0%) Moderate renal failure Advanced macrovascular complications Living alone and treated with insulin or sulfonylureas Old age with ill health Treatment with drugs that may affect mentation Patients with co morbid conditions that present additional risk factors c) Moderate risk Well-controlled diabetes treated with short-acting insulin secretagogues d) Low risk Well-controlled diabetes treated with lifestyle therapy, metformin, acarbose, thiazolidinediones, and/or incretin-based therapies in otherwise healthy patients * advised to abstain from fasting 19 Reference: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902.

20. Categories of risk in patients with Type 1 or Type 2 diabetes mellitus who fast during Ramadan 1 a) Very high risk* Severe complications within 3 months prior to fasting Severe hypoglycaemia Ketoacidosis Hyperosmolar hyperglycaemic coma Recurrent hypoglycaemia Hypoglycaemia unawareness Acute illness Sustained poor glycaemic control (HbA1c >9%) Pregnancy Advanced renal failure / Chronic dialysis b) High risk* Moderate hyperglycaemia (HbA1c 7.5–9.0%) Moderate renal failure Advanced macrovascular complications Living alone and treated with insulin or sulfonylureas Old age with ill health Treatment with drugs that may affect mentation Patients with co morbid conditions that present additional risk factors c) Moderate risk Well-controlled diabetes treated with short-acting insulin secretagogues d) Low risk Well-controlled diabetes treated with lifestyle therapy, metformin, acarbose, thiazolidinediones, and/or incretin-based therapies in otherwise healthy patients 20 Reference: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Patients Who Are at Risk of Developing Complications during Fasting * advised to abstain from fasting

21. Categories of risk in patients with Type 1 or Type 2 diabetes mellitus who fast during Ramadan 1 a) Very high risk* Severe complications within 3 months prior to fasting Severe hypoglycaemia Ketoacidosis Hyperosmolar hyperglycaemic coma Recurrent hypoglycaemia Hypoglycaemia unawareness Acute illness Sustained poor glycaemic control (HbA1c >9%) Pregnancy Advanced renal failure / Chronic dialysis b) High risk* Moderate hyperglycaemia (HbA1c 7.5–9.0%) Moderate renal failure Advanced macrovascular complications Living alone and treated with insulin or sulfonylureas Old age with ill health Treatment with drugs that may affect mentation Patients with co morbid conditions that present additional risk factors c) Moderate risk Well-controlled diabetes treated with short-acting insulin secretagogues d) Low risk Well-controlled diabetes treated with lifestyle therapy, metformin, acarbose, thiazolidinediones, and/or incretin-based therapies in otherwise healthy patients 21 Reference: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Patients Who Are at Risk of Developing Complications during Fasting * advised to abstain from fasting

22. Fasting in Special Populations with Diabetes 22 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Azad K, Mohsin F, Zargar AH, et al. Fasting guidelines for diabetic children and adolescents. Indian J Endocrinol Metab . 2012; 16(4): 516-518. Strongly advised against fasting during Ramadan 1 Fasting pregnant patients should be managed in high-risk clinics staffed by an obstetrician, diabetologist, a nutritionist, and diabetes nurse educators 1 The management of pregnant patients during Ramadan is based on an appropriate diet and intensive insulin therapy 1 Pregnant women Adolescents with good glycaemic control who do regular self-monitoring can fast safely during Ramadan 2 This is provided that a well structured program of education for both children and their families is completed prior to Ramadan, and that they receive close follow up during the month of Ramadan 2 Children and adolescents

23. Fasting in Special Populations with Diabetes 23 Most stable patients on haemodialysis and peritoneal dialysis can fast, provided that they strictly adhere to their medications and dialysis therapy in addition to the dietary restrictions 1,2 These patients should be followed-up closely to detect any complications and to ensure that adequate fluid and electrolyte balance are maintained 1,2 Dialysis patients Elderly patients are exempted from fasting. Many may wish to observe the fast 3 Those with diabetes having any degree of cognitive dysfunction, dehydration, or an increased risk of thrombosis are advised against fasting 3 Elderly patients References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Azad K, Mohsin F, Zargar AH, et al. Fasting guidelines for diabetic children and adolescents. Indian J Endocrinol Metab . 2012; 16(4): 516-518. Al Wakeel J, Mitwalli AH, Alsuwaida A, et al. Recommendations for fasting in Ramadan for patients on peritoneal dialysis. Perit Dial Int . 2013; 33(1): 86-91.

24. Glycaemic Control among Pregnant Diabetic Women on Insulin Fasting during Ramadan 24 Level of HbA1c Level of Fructosamine Reference: Ismail MNA, Raji HO, Wahab NA et al. glycaemic Control among Pregnant Diabetic Women on Insulin who fasted during Ramadan. IJMA; 2011; 36(4): 254-259. There was no statistically significant difference between the T2DM and GDM groups in terms of glycaemic control at one week before Ramadan. However, serum level of HbA1c tended to be higher in the GDM group and serum fructosamine levels tended to be lower in T2DM group. Compared to pre-Ramadan measurements, serum fructosamine levels in both groups (T2DM and GDM) were lower after Ramadan. T2DM: Type 2 diabetes mellitus ; GDM: Gestational diabetes mellitus Therefore, the findings of this study indicate that pregnant diabetic women on insulin were able to fast during Ramadan and their glycaemic control was improved during the fasting period. Onset Ramadan Middle Ramadan After Ramadan

25. Fasting during Ramadan in Children and Adolescents with Diabetes 25 *Children with Type 1 diabetes mellitus who completed Ramadan fasting Glycaemic control Weight Insulin dose Pre-Ramadan Post-Ramadan Reference: Zabeen B, Tayyeb S, Benarjee B, Baki A, Nahar J, Mohsin F, Nahar N, Azad K. Fasting during Ramadan in adolescents with diabetes. Indian J Endocr Metab 2014;18:44-7. Comparing pre-Ramadan to post-Ramadan: Glycemic control/A1c showed slight improvements No weight changes Insulin dose was increased in those who completed the Ramadan fasting Conclusion It is safe for diabetic children over the age of 11 years to fast A well-structured program of education for both children and their families is needed Close follow-up during the month of Ramadan is needed

26. Glycaemic Control in T2DM patients on Peritoneal Dialysis 26 Reference: Al Wakeel J, Mitwalli AH, Alsuwaida A, et al. Recommendations for fasting in Ramadan for patients on peritoneal dialysis. Perit Dial Int . 2013; 33(1): 86-91. Abbreviations : T2DM: Type 2 diabetes; PD: Peritoneal dialysis Pre-Ramadan Post-Ramadan The findings in the present study concluded that most stable patients on PD can fast for Ramadan provided that they are followed closely and that strict fluid and electrolyte balances are maintained. However, patients who intend to fast need comprehensive education and follow-up in the PD unit.

27. Fasting during Ramadan in Haemodialysis Patients 27 Reference: Al Wakeel; JS. Kidney function and metabolic profile of Chronic Kidney Disease and Hemodialysis patients during Ramadan fasting. IJKD. 2014; 8: 321-328. During Ramadan Before Ramadan After Ramadan p = 0.005 p = 0.22 p < 0.001 p = 0.02 Duration of haemodialysis session Total Kt/V Blood urea Serum creatinine During Ramadan, dialysis period was set to after sunset, from 7:00 PM to 10:30 PM and from 11:00 PM to 3:00 AM. Duration of the dialysis sessions was reduced to 3 to 3.5 hours. The mean duration of dialysis sessions during Ramadan was significantly different from those before and after Ramadan. Despite the shorter duration of haemodialysis sessions, Kt/V did not differ significantly. Significant changes before, during, and after Ramadan fasting were observed in the mean values of blood urea and serum creatinine. The main finding of our study was that the fasting haemodialysis patients in our cohort tolerated fasting for long hours during Ramadan. Haemodialysis must be performed after sunset and before sunrise in order for the fast to take place. Haemodialysis patients

28. Long-term Ramadan Fasting on Glucose Regulation in Elderly with T2DM 28 Reference: Karatopak C, Yolbas S, Cakirca M, Cinar A, Zorlu M, Kiskac M et al. The effects of long term fasting in Ramadan on glucose regulation in Type 2 Diabetes Mellitus. Eur Rev Med Phamaco Sci. 2013; 17: 2512-2516. Pre-Ramadan Post-Ramadan No disruption of glucose control when fasting during Ramadan No weight changes No significant increase in adverse events like hypoglycaemia, hyperglycaemia, and diabetic coma. p = 0.37 p = 0.047 p = 0.15 p = 0.73 HbA1c Fasting plasma glucose Postprandial plasma glucose Weight

29. PREPARATION PRIOR TO RAMADAN 29

30. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 30 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331.

31. Pre-Ramadan Medical Review 31 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing

32. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 32 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1

33. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 33 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2

34. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 34 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1

35. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 35 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1

36. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 36 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1

37. Pre-Ramadan Medical Review Blood pressure control Glycaemic control Lipid control Diabetes-related complications a) Assessment: 1-2 months before Ramadan Diabetes-unrelated comorbidities Overall wellbeing 37 b) Changes in diet and medication regimen To establish a safe and effective anti-diabetic regimen 1 To provide stable glycaemic control prior to start of Ramadan fast 1 d) Medical administration Anti-hypertensive dose may need to be adjusted 1 Lipid lowering medications should be continued 1 c) Pre-Ramadan consultation To reinforce healthy living advice to diabetic patients 1 To encourage diabetic patients to stop smoking 2 e) Potential risk of fasting Patients to be informed regarding the potential risk of fasting 1 f) Risk stratification of diabetic patients Recommended based on the presence of various risk factors 1 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. g) Fasting practice Diabetic patients may start to practise fasting in the months prior to Ramadan 1

38. Patient Education Hypoglycaemia – symptoms and signs Hyperglycaemia – symptoms and signs Dehydration Risk of fasting 1,2,3 During fasting During non-fasting hours Blood glucose monitoring 1,2,3 Timing Intensity Physical activity 1,2,3 Timing Dosing Medication administration 1,2,3 When to stop the fast Hydration Meal planning and food choices Management of acute complications Others 1,2,3 38 References: Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract . 2006; 73(2): 117-125. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331.

39. Proposed Algorithm for Pre-Ramadan Review and Therapeutic Regimens Adjustments 39 Reference: Almaatouq MA. Pharmacological approaches to the management of Type 2 diabetes in fasting adults during Ramadan. Diabetes Metab Syndr Obes . 2012; 5: 109-119. Acceptable control Low risk* Moderate/High risk** Current regimen Glycaemia Assess risk for hypoglycaemia Continue same regimen Adjust current regimen Patients on non-insulin agents Patients with T2DM on insulin Consider: Dietary review and advice Exercise and physical activity review and advice Address compliance issues, if any Intensify SMBG Adjust regimen Glycaemia Adjusted Ramadan regimen Poor control Acceptable control Poor control * Stable glycaemic control with no major comorbidities on metformin, glitazones, alpha glucosidase inhibitors and incretin modulators. ** Fluctuating glycaemia, major comorbidities esp. renal/hepatic insufficiency and/or use of insulin and sulfonylureas.

40. SELF-MONITORING OF BLOOD GLUCOSE (SMBG) DURING RAMADAN 40

41. Timing and Frequency of SMBG based on Treatment 41 Therapy Timing and frequency SMBG Oral anti-diabetic (OAD) Monitor when symptomatic 1 Insulin References: Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015. Hui E, Bravis V, Hassanein M, et al. Management of people with diabetes wanting to fast during Ramadan. BMJ. 2010; 340:c3053. Diabetic patients who are in the moderate to high risk categories are advised to monitor their blood glucose 5 times per day 2 Pre-meal and 2-hour post pre-dawn meal ( sahur) Mid-day Pre-meal and 2-hour post sunset meal ( iftar ) Bedtime

42. When to End the Fast during Ramadan 42 References: Pathan MF, Sahay RK, Zargar AH, South Asian Consensus Guideline: Use of insulin in diabetes during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 499-502. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. Ibrahim MA. Managing diabetes during Ramadan. Diabetes voice . 2007; 52(2): 19-22. Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010. Conditions to stop fasting: Blood glucose <3.3 mmol/l at anytime during the fast 1 Blood glucose <3.9 mmol/l in the first few hours of fasting (especially if the patient is taking sulfonylureas, meglitinides, or insulin) 2,3 Blood glucose >16.7 mmol/l 1 Experience symptoms of hypoglycaemia (patients without SMBG) 4 Symptoms suggestive of severe dehydration such as syncope and confusion 4

43. Timing of SMBG Could Reflect Adequacy of Insulin Dose 43 Insulin type Premixed / bolus / basal insulin Premixed / basal insulin Premixed / basal insulin Premixed / basal insulin Premixed / bolus insulin Insulin timing Pre- sahur Pre- sahur Pre- iftar Pre- iftar / Pre-bed Pre- sahur Time of glucose monitoring Mid-day Pre- iftar 2-hour post- iftar or bedtime Pre- sahur 2-hour post- sahur Reference: Pathan MF, Sahay RK, Zargar AH, South Asian Consensus Guideline: Use of insulin in diabetes during Ramadan. Indian J Endocrinol Metab . 2012; 16(4): 499-502.

44. LIFESTYLE AND DIET MANAGEMENT DURING RAMADAN 44

45. Meal Planning Appropriate meal planning is important to avoid postprandial hyperglycaemia 1 The diet during Ramadan should not differ from a healthy balanced diet 1 Consume slow-energy food 3 (i.e. wheat, beans and rice) Distribute calories over two to three smaller meals during the non-fasting interval 2 45 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care . 2010; 33(8): 1895-902. Persatuan Dietitian Malaysia. Medical Nutrition Therapy Guidelines for Type 2 Diabetes Mellitus. 2013. Second Edition. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331.

46. Dietary Advice 46 Reference: Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015. Good “ buka puasa” meal Food that should be limited during “ buka puasa” A B

47. Adjustment of Diet Protocol for Ramadan Fasting 47 Reference: Persatuan Dietitian Malaysia. Medical Nutrition Therapy Guidelines for Type 2 Diabetes Mellitus. 2013. Second Edition. Never skip sahur (dawn meal) Do not delay “ berbuka ” Supper after Tarawih can be taken as replacement of pre-bed snack Include fruits and vegetables at both sahur and iftar Limit fried and fatty foods Limit intake of highly salted foods to reduce risk of dehydration Drink adequately at sahur , choose sugar-free drinks, aim for 8 glasses per day Avoid excessive binging of carbohydrates during non–fasting period

48. Physical Activity 48 References: Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med . 2010; 103(4): 139-147. Ibrahim MA. Managing diabetes during Ramadan. Diabetes voice . 2007; 52(2): 19-22.

49. Management of Hypoglycaemia during Ramadan Patients need to end their fast if they experience symptoms of hypoglycaemia or have low blood glucose values* Take simple carbohydrates 49 Reference: Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015. *Refer to Section 7: Self-monitoring of blood glucose during Ramadan: Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015. *Blood glucose < 3.3 mmol/l at anytime during the fast. *Blood glucose < 3.9 mmol/l in the first few hours of fasting (especially if the patient is taking sulfonylureas, meglitinides, or insulin). *Experience symptoms of hypoglycaemia (patients without SMBG). *Symptoms suggestive of severe dehydration such as syncope and confusion.

50. ORAL ANTI-DIABETIC THERAPY DURING RAMADAN 50

51. Oral Anti-Diabetic Therapy during Ramadan 51 References: Al-Arouj M, Hassoun AA, Medlej R, et al. The effect of vildagliptin relative to suAl-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010; Diabetes Care . 2010; 33(8): 1895-902 Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab. 2012; 16(4): 503-507. Mafauzy M. Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting. Diabetes Res Clin Pract . 2002; 58(1): 45-53. Glimepiride in Ramadan (GLIRA) Study Group. The efficacy and safety of glimepiride in the management of Type 2 diabetes in Muslim patients during Ramadan. Diabetes Care . 2005; 28(2): 421-422. Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015.

52. Adjustment of Oral Anti-Diabetic Therapy during Ramadan 52 Reference: Almaatouq MA. Pharmacological approaches to the management of Type 2 diabetes in fasting adults during Ramadan. Diabetes Metab Syndr Obes . 2012; 5: 109-119. Regimen Sunset meal ( iftar ) Pre-dawn meal ( sahur ) α- glucosidase inhibitors Biguanides (Metformin) Thiazolidinediones Sodium glucose co-transporter 2 inhibitors* Dipeptidyl peptidase-4 inhibitors Meglitinides No changes No changes No changes Two third of dose No changes One third of dose No changes No changes No changes No changes No changes Sunset meal dosing No changes None Sulphonylurea Glibenclamide, Gliclazide Gliclazide modified-release, Glimepiride No changes Reduce / Omit Sunset meal dosing Immediate-release Twice daily Thrice daily Extended-release Full dose None * Based on expert opinion

53. Safety and Efficacy of Vildagliptin during Ramadan (VIRTUE study) 53 P < 0.001 P = 0.053 Number of patients with hypoglycaemic events during Ramadan Mean change HbA1c pre- to post-Ramadan P < 0.001 Mean change body weight pre- to post-Ramadan P < 0.001 Vildagliptin Sulphonylurea Vildagliptin therapy was associated with significantly fewer patients experiencing hypoglycaemia compared with SU therapy in this large representative cohort of fasting Muslim patients with Type 2 diabetes mellitus. This outcome is particularly meaningful when viewed in the context of good glycaemic and weight control observed in vildagliptin-treated patients who fasted in this study. Vildagliptin was well-tolerated in this patient population. Reference: Al-Arouj M 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(10): 957-963. Hypoglycaemia events Hypoglycaemia events

54. The Incidence of Hypoglycaemia with T2DM Treated with Sitagliptin during Ramadan 54 Reference: Al Sifri, Basiounny A., Echtay A., Al Omari M., Harman-Boehm I., Kaddaha G. et al. The incidence of hypoglycaemia in Muslim patients with Type 2 diabetes treated with sitagliptin or a sulponylurea during Ramadan: a randomised trial. Int J Clin Pract. 2011; 65(11): 1132- 1140. Sitagliptin Sulphonylurea The proportion of patients with either symptomatic or asymptomatic hypoglycaemic events was 8.5% in the sitagliptin group and 17.9% in the gliclazide group. The incidence of hypoglycaemic events requiring non-medical assistance was low, with 0.2% of patients in the sitagliptin group and 0.8% in the gliclazide group. In Muslim patients with Type 2 diabetes who observed the fast during Ramadan, switching treatment to a sitagliptin-based regimen decreased the risk of hypoglycaemia compared with a sulphonylurea-based regimen. Both treatment regimens were generally well tolerated during the month of Ramadan. Symptomatic or asymptomatic hypoglycaemic events Hypoglycaemic events requiring non-medical assistance 8.5% 17.9% 0.2% 0.8%

55. Safety and Efficacy of Gliclazide during Ramadan (STEADFAST study) 55 P = 0.039 Number of patients with hypoglycaemic events during Ramadan Mean change HbA1c pre- to post-Ramadan p = 0.165 Mean change body weight pre- to post-Ramadan p = 0.423 Vildagliptin Gliclazide Glycaemic control, assessed as changes in HbA1c remained stable pre- to post-Ramadan with both treatments, indicate that similar efficacy can be achieved during the Ramadan fasting period with vildagliptin and gliclazide. In both treatment groups, a small decrease in body weight from pre- to post-Ramadan was observed. The proportion of patients who reported any hypoglycaemia events during the Ramadan fasting period was numerically lower in the vildagliptin compared with the gliclazide; however, the difference between treatments did not reach statistical significance. Reference: Hassanein M, Abdallah K, Schweizer A. A double-blind, randomized trial, including frequent patient-physician contacts and Ramadan focused advice, assessing vildagliptin and gliclazide in patients with Type 2 diabetes fasting during Ramadan: the STEADFAST study. Vasc Health Risk Management. 2014; 4(10): 319-326. Hypoglycaemia events The results suggest that the lower hypoglycaemia rate for gliclazide seen in the present study may be linked to the special conditions of the STEADFAST study, in which the particular attention to each patient, Ramadan-focused advice, the recent switch in treatment, as well as the patients’ very good glycaemic control have created a setting that is often not reflected in real life.

56. Safety and Efficacy of Glimepiride during Ramadan (GLIRA study) 56 HbA1c value (%) FBG value (mmol/l) Newly diagnosed subjects Already treated subjects V0: Baseline V1: Just before, or no more than 5 days after, the start of Ramadan, V3: Between 45 and 75 days after the end of Ramadan The efficacy and safety of glimepiride in Type 2 diabetic patients is not altered during the month-long daylight fast of Ramadan, when the time of administration of glimepiride is changed from the morning to the evening. It can be concluded that with careful dietary management and a change in the time of drug administration from morning to evening, Muslim Type 2 diabetic patients taking glimepiride who are normally well controlled can fast during Ramadan if they wish to do so, with no deterioration of glycaemic control. Reference: GLIRA Study Group. The Efficacy and Safety of Glimepiride in the Management of Type 2 Diabetes in Muslim Patients During Ramadan . Diab Care . 2005; 28(2): 9421-422.

57. INSULIN THERAPY DURING RAMADAN 57

58. Insulin Adjustment during Ramadan – Basal Insulin Insulin regimen Type 1 diabetes mellitus Type 2 diabetes mellitus Basal insulin only 1-4 Not applicable. Taken at bedtime or any time after iftar meals. May require dose reduction if there is risk of daytime hypoglycaemia. 58 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update. 2010. Diabetes Care. 2010; 33(8): 1895-902. Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010. Pathan MF, Sahay RK, Zargar AH, South Asian Consensus Guideline: Use of insulin in diabetes during Ramadan. Indian J Endocrinol Metab. 2012; 16(4): 499-502. Hui E, Devendra D. Diabetes and fasting during Ramadan. Diabetes Metab Res Rev. 2010; 26(8): 606-610. Insulin glargine can be given once daily any time after iftar. Insulin levemir and NPH insulin can be given either once daily at bedtime or divided into twice daily during pre-dawn meal ( sahur ) and iftar . 1

59. Insulin Adjustment during Ramadan – Premixed Insulin Insulin regimen Type 1 diabetes mellitus Type 2 diabetes mellitus Premixed insulin once daily 1-4 Not applicable. Inject usual dose at iftar meals. Premixed insulin twice daily 1-5 Reverse doses Morning dose given at iftar and evening dose given at sahur. Sahur Insulin dose reduced by 20-50% to prevent daytime hypoglycaemia. Insulin dose reduced by 20-50% to prevent daytime hypoglycaemia. OR Change to short/rapid acting.* * Late afternoon hypoglycaemia may occur Iftar Switch to mid/high premixed ( ie . Mix50) insulin 59 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update. 2010. Diabetes Care. 2010; 33(8): 1895-902. Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010. Pathan MF, Sahay RK, Zargar AH, South Asian Consensus Guideline: Use of insulin in diabetes during Ramadan. Indian J Endocrinol Metab. 2012; 16(4): 499-502. Hui E, Devendra D. Diabetes and fasting during Ramadan. Diabetes Metab Res Rev. 2010; 26(8): 606-610. Hui E, Bravis V, Salih S, et al. Comparison of Humalog Mix 50 with human insulin Mix 30 in type 2 diabetes patients during Ramadan. Int J Clin Pract . 2010; 64(8): 1095–1099.

60. Insulin Adjustment during Ramadan – Basal Bolus Insulin and Insulin Pump Insulin regimen Type 1 diabetes mellitus Type 2 diabetes mellitus Basal bolus insulin 1-4 Basal insulin Taken at bedtime or any time after iftar meals. May require dose reduction if there is daytime hypoglycaemia. Bolus/Prandial insulin Sahur Lunch Iftar Usual pre-Ramadan breakfast or lunch dose. May require dose reduction to avoid daytime hypoglycaemia. Omit. Usual pre-Ramadan dinner dose. May require dose increment. * Total insulin requirement for Type 1 diabetics who are on basal bolus insulin regimen while fasting during Ramadan may require dose reduction 15‒30% of their pre-Ramadan dose requirements. Insulin pump 5-7 Basal insulin rate Unchanged or may require reduction of up to 25%. Prandial bolus According to individualised insulin to carbohydrate ratio (ICR). 60 References: Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update. 2010. Diabetes Care. 2010; 33(8): 1895-902. Ministry of Health Malaysia. Practical guide to Insulin Therapy in Type 2 Diabetes Mellitus. 2010. Pathan MF, Sahay RK, Zargar AH, South Asian Consensus Guideline: Use of insulin in diabetes during Ramadan. Indian J Endocrinol Metab. 2012; 16(4): 499-502. Hui E, Devendra D. Diabetes and fasting during Ramadan. Diabetes Metab Res Rev. 2010; 26(8): 606-610. Bin-Abbas BS. Insulin pump therapy during Ramadan fasting in Type 1 diabetic adolescents. Ann Saudi Med. 2008; 28(4): 305-306. Hawli YM, Zantout MS, Azar ST. Adjusting the basal insulin regimen of patients with Type 1 diabetes mellitus receiving insulin pump therapy during the Ramadan fast: A case series in adolescents and adults. Curr Ther Res Clin Exp. 2009; 70(1): 29-34. Benbarka MM, Khalil AB, Beshyah SA, et al. Insulin pump therapy in Moslem patients with Type 1 diabetes during Ramadan fasting: an observational report. Diabetes Technol Ther. 2010; 12(4): 287-290. Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015.

61. Basal Insulin Regimen Adjustment during Ramadan 61 HbA1c value Basal insulin dose 0% -9.4% -24.1% -5.5% -25.0% 0.5% 0.9% 0.3% 0% 0.1% Appropriate adjustment of basal insulin dosing in patients with T1DM who desire to fast can help them maintain glycaemic control. It is recommended to decrease the basal requirement by 5.5% to 25% under physician supervision. No. of Patients No. of Patients Pre-Ramadan Post-Ramadan Reference: Hawli YMA et al. Adjusting the Basal Insulin Regimen of Patients With Type 1 Diabetes Mellitus Receiving Insulin Pump Therapy During the Ramadan Fast: A Case Series in Adolescents and Adults . Curr Ther Res . 2009; 70(1): 29-34.

62. Insulin Pump Therapy during Ramadan 62 Nearly half of the patients decreased their basal insulin rate by 5–50%; median reduction was 14%. The HbA1c value was maintained before and during Ramadan . In conclusion, fasting during Ramadan is feasible for patients with Type 1 diabetes on insulin pumps with adequate counseling and support. HbA1c value Reference: Benbarka MM et al. Insulin Pump Therapy in Moslem Patients with Type 1 Diabetes During Ramadan Fasting: An Observational Report . Diab Tech Ther . 2010; 12(4): 287-290.

63. Summary of Treatment Algorithm 63 Evaluate risk of developing complications during Ramadan Advised to abstain from fasting Reference: Ministry of Health (MOH) Malaysia. Practical Guide to Diabetes Management in Ramadan 2015. Very high risk High risk Moderate risk Low risk Pre-Ramadan medical review Performed 1-2 months before Ramadan Approach should be individualised Assessment of glycaemic control, blood pressure, and lipids Structured Ramadan-focused patient education Meal planning and dietary advice with a dietitian Appropriate timing and intensity of exercise Blood glucose monitoring Knowing when to end the fast Recognising and managing acute complications Treatment adjustments Changes to diabetes medication regimes: Treatment choice Timing and frequency of dosing Dosage adjustments Follow-up is essential after Ramadan HbA1c, blood pressure, lipids Readjustment of medications where appropriate Revert back to pre-Ramadan treatment regimen

64. Key Messages Many Muslims with diabetes choose to fast during Ramadan even though they are exempted from it due to their health conditions. 1 Fasting is associated with excessive glycogen breakdown, increased gluconeogenesis and ketogenesis leading to hyperglycaemia and ketoacidosis. 2,3 Fasting during Ramadan may be associated with improvements in glycaemic control, blood pressure, high-density lipoprotein (HDL) levels and body weight. 4-8 Diabetic patients who fast are at higher risk of hypoglycaemia, hyperglycaemia and ketoacidosis with increased rate of hospitalisation. 9,10 Risk stratification is important to identify patients who are at risk of developing complications during fasting. 2 Pre-Ramadan medical review and education concerning self-care during Ramadan is important. 2,3, 11-14 Regular glucose monitoring is recommended during Ramadan. 2 a) Appropriate meal planning is important to avoid postprandial hyperglycaemia. 14 b) Appropriate modification in intensity and timing of physical activity is important to maintain optimal glycaemic control and optimal weight. 3,14 Adjustment for oral anti-diabetic medications and insulin should be individualised to lower the risk of hypoglycaemia when fasting during Ramadan. 2,16 64 References: Salti I, Bénard E, Detournay B, et al. A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care. 2004; 27(10): 2306-2311. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update. 2010. Diabetes Care. 2010; 33(8): 1895-902. Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med. 2010; 103(4): 139-147. Mafauzy M, Mohammed WB, Anum MY, et al. A study of the fasting diabetic patients during the month of Ramadan. Med J Malaysia. 1990; 45(1): 14-17. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract. 2006;73(2): 117-125. Chamakhi S, Ftouhi B, Rahmoune NB, et al. Influence of the fast of Ramadan on the balance glycaemic to diabetics. Medicographia. 1991; 13: 27-29. Perk G, Ghanem J, Aamar S, et al. The effect of the fast of Ramadan on ambulatory blood pressure in treated hypertensives. J Hum Hypertens. 2001; 15(10): 723-725. Akturk IF, Biyik I, Kocas C, et al. PP-014 The effect of Ramadan fasting on blood pressure levels of hypertensive patients with combination therapy. Int J Cardiol. 2012; 155(Suppl 1): S103. Salti I, Bénard E, Detournay B, et al A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care. 2004; 27(10): 2306-2311. Loke SC, Rahim KF, Kanesvaran R, et al. A prospective cohort study on the effect of various risk factors on hypoglycaemia in diabetics who fast during Ramadan. Med J Malaysia. 2010; 65(1): 3-6. Bashir MI, Pathan MF, Raza SA, et al. Role of oral hypoglycaemic agents in the management of Type 2 diabetes mellitus during Ramadan. Indian J Endocrinol Metab. 2012; 16(4): 503-507. Benaji B, Mounib N, Roky R, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract. 2006;73(2): 117-125. Hui E, Devendra D. Diabetes and fasting during Ramadan. Diabetes Metab Res Rev. 2010; 26(8): 606-610. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med. 2010; 27(3): 327-331. Persatuan Dietitian Malaysia. Medical Nutrition Therapy Guidelines for Type 2 Diabetes Mellitus. 2013. Second Edition. Almaatouq MA. Pharmacological approaches to the management of Type 2 diabetes in fasting adults during Ramadan. Diabetes Metab Syndr Obes . 2012; 5: 109-119.

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66. References 66 Bin-Abbas BS. Insulin pump therapy during Ramadan fasting in Type 1 diabetic adolescents. Ann Saudi Med . 2008; 28(4): 305-306. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med . 2010; 27(3): 327-331. Chamakhi S, Ftouhi B, Rahmoune NB, et al. Influence of the fast of Ramadan on the balance glycaemic to diabetics. Medicographia . 1991; 13: 27-29. Cheng CW, Adams GB, Perin L, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014; 14(6): 810-823. Dikensoy E, Balat O, Cebesoy B, Ozkur A, Cicek H, Can G. The effect of Ramadan fasting on maternal serum lipids, cortisol levels and fetal development. Arch Gynecol Obstet 2009; 279: 119–23. Glimepiride in Ramadan (GLIRA) Study Group. The efficacy and safety of glimepiride in the management of Type 2 diabetes in Muslim patients during Ramadan. Diabetes Care . 2005; 28(2): 421-422. GLIRA Study Group. The Efficacy and Safety of Glimepiride in the Management of Type 2 Diabetes in Muslim Patients During Ramadan . Diab Care . 2005; 28(2): 9421-422. Hassanein M, Abdallah K, Schweizer A. A double-blind, randomized trial, including frequent patient-physician contacts and Ramadan focused advice, assessing vildagliptin and gliclazide in patients with Type 2 diabetes fasting during Ramadan: the STEADFAST study. Vasc Health Risk Management. 2014; 4(10): 319-326. Hawli YM, Zantout MS, Azar ST. Adjusting the basal insulin regimen of patients with Type 1 diabetes mellitus receiving insulin pump therapy during the Ramadan fast: A case series in adolescents and adults. Curr Ther Res Clin Exp . 2009; 70(1): 29-34. Hui E, Devendra D. Diabetes and fasting during Ramadan. Diabetes Metab Res Rev . 2010; 26(8): 606-610. Hui E, Bravis V, Salih S, et al. Comparison of Humalog Mix 50 with human insulin Mix 30 in type 2 diabetes patients during Ramadan. Int J Clin Pract . 2010; 64(8): 1095–1099. Ibrahim MA. Managing diabetes during Ramadan. Diabetes voice . 2007; 52(2): 19-22.

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