1. Ref: https://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.htmlhttps://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.html A Real Challenge? Prof. Taj Jamshaid MB, FCPS, FPSIM, CHPE, MACG Sharif Medical & Dental College/ Sharif City Hospital, Lahore drjamshaid1@gmail.com Prof. Taj Jamshaid MB, FCPS, FPSIM, CHPE, MACG Sharif Medical & Dental College/ Sharif City Hospital, Lahore drjamshaid1@gmail.com

2. Disclaimer No conflict of interests Educational activity without any financial benefits Trade names used for better understanding and orientation and NOT for any monetary gain

3. DM – major and independent risk factor for both microvascular and macrovascular complications World Health Organization. http://www.who.int/diabetes/action_online/basics/en/index3.html Macrovascular Microvascular Coronary artery disease (CAD) Cerebrovascular disease (e.g., stroke) Peripheral vascular disease Kidney disease (Nephropathy) Eye Disease (Retinopathy) Neuropathy Symmetric Polyneuropathy Autonomic neuropathy Silent Disease / syndrome ? Diabetes…

4. Diabetes Burden in Pakistan

5. Islam has 1.9 billion (24.7% of the world population) adherents Growing by ~3% per year South Asia has the largest population of Muslims in the world (1/3 rd of all Muslims)* Ramadan: 1 of the 5 pillars of Islam Holy month for Muslims, and The month when The Quran was revealed to Prophet Muhammad *https://en.wikipedia.org/wiki/Islam_by_country

6. (Surah Baqra: Ayat 185) “Whoever witnesses the month (of Ramadan) then he/she should fast. But, if any of you is ill or travelling-then he or she is exempted from fasting’ and ‘the missed fast should be completed at another time”. “Whoever witnesses the month (of Ramadan) then he/she should fast. But, if any of you is ill or travelling-then he or she is exempted from fasting’ and ‘the missed fast should be completed at another time”. The Holy Quran says that Fasting during Ramadan, is a duty for all healthy adult Muslims

7. Many Muslims, even those who could seek exemption, have an intense desire to participate in fasting during Ramadan. Exempted categories include Children, the Sick, Travelers, women during menses and anyone with reduced mental capacity

8. Despite the exemption, many people with diabetes fast during Ramadan EPIDIAR study (2001) ** 42.8% T1DM 78.7% T2DM (fasted for at least 15 days during Ramadan) EPIDIAR study (2001) ** 42.8% T1DM 78.7% T2DM (fasted for at least 15 days during Ramadan) * Babineaux, S.M., et al., Multi-country retrospective observational study of the management and outcomes of patients with Type 2 diabetes during Ramadan in 2010 (CREED). Diabet Med, 2015. 32(6): p. 819-28. ** Salti, I., 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): p. 2306-11. *** Hassanein, M., et al., The characteristics and pattern of care for the type 2 diabetes mellitus population in the MENA region during Ramadan: An international prospective study (DARMENA T2DM). Diabetes research and clinical practice, 2019. 151: p. 275-284. DAR-MENA T2DM study *** 86% of participants fasted for at least 15 days DAR-MENA T2DM study *** 86% of participants fasted for at least 15 days *CREED Study 2010; Percentage of patients with T2DM fasting for specific period during Ramadan

9.  Changes in sleeping patterns and circardian rhythms  In a healthy individual, fasting causes the release of glucose from glycogen stores (glycogenolysis) & the formation of glucose from non-CHO substrates (gluconeogenesis) Sudden shift in mealtimes, sleep and wakefulness patterns, leading to physiological changes in the homeostatic and endocrine processes Pathophysiology of fasting in individuals with diabetes

10. As diabetes is metabolic in nature, any major changes in the diet and fluid intake leads to an increased risk of complications such as

11. Biggest Risk The Risk of Hypoglycemia is based on Previous h/o hypoglycaemias A tight control Renal disease Liver disease Frailty Insulins Secretagogues

12. Medical professionals/ HCPs Be aware of the potential risks associated with fasting during Ramadan Must know the approaches to mitigate those risks AIM: To prevent hypoglycemia & (severe) hyperglycemia during fasting

13. Ref: https://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.htmlhttps://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.html Pre-Ramadan Assessment & Education

14. Structured Education for all individuals include:

15. PRE-RAMADAN All individuals seeking to fast should attend a pre-Ramadan visit 6 – 8 weeks before Ramadan To stratify risk and develop an individual management plan 1.Detailed medical history 2.Aspects of diabetes 3.Presence of comorbidities 4.The individual’s prior experience in managing diabetes during Ramadan Fasting 5.The individual’s ability to self-manage diabetes ASSESSMENT Risk stratification: Low, Moderate and High

16. DURING RAMADAN Frequency of SMBG needs to be guided by risk stratification and individualized o Blood glucose < 70 mg/dl (3.9 mmol/L) o Re-check within 1 hour if blood glucose 70-90 mg/dl (3.9-5.0 mmol/L) o Blood glucose levels > 300 mg/dl (16.6 mmol/L)* o Symptoms of hypoglycemia or acute illness occur ALL INDIVIDUALS SHOULD BREAK THEIR FAST IF: POST-RAMADAN ASSESSMENT POST- RAMADAN SMBG, self-monitoring blood glucose *This applies for those with sudden rise in blood glucose level, individization of care is advisable

17. Ref: https://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.htmlhttps://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.html Risk Stratification

18. Factors for Risk Quantification Type of Diabetes Medications Individual hypoglycemic risk Presence of complications and/or comorbidities Individual social and work circumstances Previous Ramadan experience This assessment exercise must be individualized for everyone looking to fast during Ramadan, and personalized care must be provided accordingly

19. Elements for Risk Calculation & suggested Risk Score for people with DM that seek to Fast during Ramadan

20. LOW RISK Score 0 to 3 MODERATE RISK Score 3.5 to 6 HIGH RISK Score > 6 Fasting is probably Safe 1.Medical Evaluation 2.Medication Adjustment 3.Strict Monitoring Fasting Safety is Uncertain 1.Medical Evaluation 2.Medication Adjustment 3.Strict Monitoring Advise against fasting MEDICAL & RELIGIOUS RISK SCORE CATEGORIES & RECOMMENDATION 1.Fasting is Obligatory 2.Advised to Fast, unless you are unable due to the physical impact of fasting or having to take medication, food or drink during fasting hours 1.Fasting is recommended, but you can choose not to fast if concerned about health after consulting 2.If choose to fast, must follow medical recommendations, including regular BGM Fasting is probably Unsafe

21. Type 1 diabetes Pregnancy CKD 4-5 Decompensated CLD Heart failure, NYHA class 3-4 Any disease requiring frequent medications Any patient who is too unwell Patient’s choice

22. SMBG: Self monitoring of blood glucose helps people with diabetes in effective self- management A 7 point blood glucose monitoring guide for people with diabetes fasting during Ramadan

23. Ref: https://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.htmlhttps://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.html Exercise

24. Physical exertions in Tarawih prayers, such as bowing, kneeling and rising, should be considered as part of the daily exercise activities. Rigorous exercise – not recommended during fasting because of the increased risk of hypoglycemia and/or dehydration Encourage regular light-to-moderate exercise during Ramadan Exercise: Practical Guidelines

25. Dietary advice for patients with diabetes during Ramadan Divide daily calories b/w Suhoor and Iftar, plus 1 – 2 snacks if necessary Ensure meals are well balanced 45-50% Carbohydrate 20-30% protein <35% fat (preferably mono- and polyunsaturated) Include low glycemic index, high fiber foods (granary bread, beans, rice) Avoid sugary deserts Include plenty of fruit, vegetable and salads Minimize high saturated fat foods (ghee, samosas, pakoras) Use small amounts of oil when cooking (olive, rapeseed) Keep hydrated between Iftar and Suhoor by drinking water or other non-sweetened beverages Avoid caffeinated & sweetened drinks

26. Weight maintenanceWeight reduction Men Women > 150 cm tall Women < 150 cm tall 1800 – 2200 kcal/day 1500 – 2000 kcal/day 1500 kcal/day 1800 kcal/day 1200 kcal/day Daily caloric intake distribution during Ramadan Percentage of total calories/day Suhoor30 – 40% Iftar 40 – 50% Snacks b/w meals (1 or 2, if necessary)40 – 50% Caloric targets for men and women during Ramadan

27. Example of a Ramadan Plate 1 glass of low fat milk 1 – 2 dates 1 small slice of watermelon 2 teaspoon of oil 1 cup of vegetables 1.5 cup of whole grain rice 4 oz of lean protein ½ cup of beans/lentils/peas This meal provides: 770 kcal, 45% carbohydrates, 20% protein and 35% fat

28. Ref: https://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.htmlhttps://idf.org/e-library/guidelines/165-idf-dar-practical-guidelines-2021.html Medication Adjustments

29. Anti-Diabetic Drugs – Hypoglycemia? LOW RISK MODERATE RISK HIGH RISK Metformin SGLT2 inhibitors Acarbose Thiazolidinediones DPP4 inhibitors GLP1-RA NG-SU: Glimepiride Gliclazide-MR Basal insulin Basal insulin with GLP-RA combo OG-SU: Glibenclamide Intermediate acting insulin (NPH) Pre-Mix human insulin

30. METFORMIN (Glucophage) Monotherapy No No dose modification usually required Morning dose to be taken before Suhoor No No dose modification usually required XR I m m e d i a t e r e l e a s e Prolonged release

31. DPP – IV inhibitors Monotherapy Sitagliptin (Sita, Inosita, Trevia) Vildagliptin (Galvus, Vilget) Linagliptin (Lina, Linvesta) DPP – IV inhibitors & Metformin Combos Sitagliptin + Metformin (Sitamet, Inosita plus, Treviamet) Vildagliptin + Metformin (Galzamet, Vilget-M) Sitagliptin + Metformin XR One of the best tolerated OADs with low risk of hypoglycemia No Change Necessary

32. In In patients with well-controlled BG levels the dose may be reduced 2 nd -generation SUs (glicazide, glimepiride) should be prefered SULPHONYLUREA Older drugs (e.g. glibenclamide) as mono or combo with metformin should be avoided The risk of hypoglycemia in those treated with Gliclazide MR seems to be low as shown in a recent study while maintaining good glycemic control

33. SGLT2 inhibitors Empagliflozin (Diampa or Jardy) Dapagliflozin (Dapa or Xiga) Ertugliflozin (Ertuvia) Ertugliflozin+Sitagliptin (TreviaR2) SGLT2 inhibitors & Metformin Dapagliflozin + Metformin (Dapamet or Xigamet) Empagliflozin + Metformin (Diampa- M or Glempa-M) Ertugliflozin + Metformin (Ertuvia-M) No dose adjustment Take with Iftar Continue as such if no significant diuresis Replace morning dose with metformin alone Due to safety concerns – NOT recommended for some patients during Ramadan The elderly Patients with Renal impairement Hypotensive individuals Those at risk of Dehydration Those taking Diuretics

34. Pioglitazone Monotherapy & Combos Pioglitazone (Piozer, Zolid) Pioglitazone + Metformin (Zolid Plus) Alpha Glucosidase Inhibitor Acarbose (Glucobay) No dose change Continue as such No dose change Continue as such Drop afternoon dose if TDS

35. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) Liraglutide (Victoza) Dulaglutide (Trulicity) Semaglutide (Ozempic) Once appropriate dose titration achieved, No further dose modifications needed

36. Changes to Long-acting & Short-acting Insulin dosing NPH/Detemir/Glargine Once Daily ↓ dose by 15-30% Take at Iftar Long/intermediate-acting (Basal) InsulinShort-acting (Bolus) Insulin NPH/Detemir/Glargine Twice Daily Take usual morning dose at Iftar ↓ evening dose by 50% & take at Suhoor Normal dose at Iftar Omit lunch-time dose ↓ Suhoor dose by 25-50% Fasting/pre-iftar/pre-suhoor BGPre-iftarPost-iftar/post-suhoor Basal InsulinShort-acting Insulin <70 mg/dl (3.9 mmol/L) or symptoms↓ by 4 U 70-90 mg/dl (3.9-5.0 mmol/L)↓ by 2 U 90-130 mg/dl (5.0-7.2 mmol/L)No change

37. Changes to Premixed Insulin dosing Take Normal dose at Iftar One-Daily dosing Fasting/pre-iftar/pre-suhoor BGPremixed Insulin modification <70 mg/dl (3.9 mmol/L) or symptoms↓ by 4 U 70-90 mg/dl (3.9-5.0 mmol/L)↓ by 2 U 90-126 mg/dl (5.0-7.0 mmol/L)No change 126-200 mg/↑ by 2 U Take Normal dose at Iftar ↓ Suhoor dose by 25-50% Twice-Daily dosing Omit afternoon dose Adjust Iftar and Suhoor doses Carry out dose-titration every 3 days (see below) Three times Daily dosing

38. Basal Insulin & GLP1-RA Combo Insulin Degludec + Liraglutide (Xultophy) Insulin Glargine + Lixisenatide (Soliqua) Pre-Ramadan FPG ≥120 mg/dl: Same dose may be continued Pre-Ramadan FPG <120 mg/dl: Reduce dose by 20% (e.g 30-20% = 24)

39. Many diabetic patients despite exemption, have an intense desire to participate in fasting during Ramadan. All individuals seeking to fast should attend a pre-Ramadan visit 6 – 8 weeks before Ramadan for Structured Education. Pre-Ramadan assessment, counselling and appropriate adjustment in medication is recommended. Medicines with low potential of causing hypoglycemia are preferred. Medication adjustment is advised to reduce the risk of complications especially hypoglycemia and severe hyperglycemia. Take Home Message

40. Thanks for the attention Have Healthy & Blessed Ramadan Thanks for the attention Have Healthy & Blessed Ramadan Taj Jamshaid drjamshaid1@gmail.com Taj Jamshaid drjamshaid1@gmail.com