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Fasting and Medical Issues During Ramadan Dr Wafa Ababtain .MD 21,may,2012 • Introduction • Metabolic effect of Ramadan fasting • Medical Issues in Ramadan - Cardiac patient and fasting - stroke in Ramadan - kidney transplantation and fasting - peptic ulcer disease -chronic liver disease - DM • conclusion 2009 demographic study, Islam has 1.57 billion adherents, making up 23% of the world population of 6.8 billion, and is growing by ∼3% per year Important facts about Ramadan • Ramadan is the 9th month of the Hijry calendar year in which the holy Qur”an was revealed to islams” holy prophet. • The Islamic calendar is lunar and the start of the islamic year advances 11 days each year compared with the seasonal year. • Ramadan occurs at different times of the seasonal year over a 33-year cycle . • This can result in the Ramadan fast being undertaken in markedly different environmental conditions between years in the same country (a different season every 9 years) • The time of sunrise and sunset varies between 12 h at the equator and about 22 h at the 64* of latitude in summertime. • Not only is the eating pattern greatly altered during the Ramadan period, but the amount and type of food eaten during the night may also be significantly different to that usually consumed during the rest of the year. • In many cultures, special festival foods that are richer in fat and protein than the usual diet, or that contain large quantities of sugar, are eaten. • Muslims observing the fast must not only abstain from eating and drinking, but also from taking oral medications, smoking, as well as receiving intravenous fluids and nutrients carbohydrate metabolism during experimental short-term fasting 1- Post-absorptive period for the first 8-16 hrs after eating. 2- Glycogenlysis 1,200 calories are stored as carbohydrate in the liver providing the basal requirement for glucose for only 5–6 h. 3- Gluconeogenesis refers to the formation of glucose from lactate, pyruvate, amino acids and glycerol. 4- lipolysis -fatty acid oxidation and keton body formation which replaces glucose as the essential fuel for use by other tissues of the body Metabolic effects of Ramadan fasting • Fasting is associated with improvement in several hemostatic risk markers for cardiovascular disease. • Reduction in plasma triglyceride and plasma LDLcholesterol level. • Improvement in insulin sensitivity, leptin, adiponectin and HDL cholesterol. • Reduction in plasma homocysteine, D-dimer level, Creactive protein (CRP) and IL-6 and fibrinogen. • Similar beneficial effects of fasting have been reported in diabetic individuals. Cardiac patients and Ramadan fasting • Whether Ramadan fasting has any adverse effect on their cardiac status ? • The answer has not yet been clarified. • Ramadan may have negative effects on cardiovascular disease patients, the obligation that the daily calorie intake has to be taken in one or two meals instead of three to five, is an effort. • In Ramadan medications may not be taken regularly. Is there any effect of Ramadan fasting on acute coronary heart disease events 1 • A. Temizhana reported in his retrospective study 1991 - 1997 during ,befor ,and after Ramadan • 1655 of 5016 patients were found to have acute coronary heart disease events. • The ratios of the cases with acute coronary heart disease to all patients were not statistically significant (P value > 0.05) • No significant difference was found in mortality rates of patient with acute coronary heart disease events between the periods (P value > 0.05) 1 -International Journal of Cardiology 70 (1999) • retrospective review in Qatar on all Qatari patients who were hospitalized with heart failure for a period of 10 years (1991 - 2001) . • The number of hospitalization for patients with CHF was compared between the month of Ramadan and one month befor and one month after. • 2160 patients were hospitalized for CHF. • The overall mortality was 9.7%. • The number of hospitalization for CHF was not significantly different in Ramadan (208 cases) when compared to a month before Ramadan (182 cases) and a month after Ramadan (198 cases) p > 0.37. • There was no significant difference in the baseline clinical characteristics or mortality (11.5%, 7.7% and 9.6%, respectively; p>0.43). • Fasting patients are under volume deprivation and, possibly, salt restriction • This might explain reducing the signs and symptoms of HF and the hospitalization during the month of Ramadan. J. Al Suwaidi et al. / International Journal of Cardiology 96 (2004) 217–221 Impact of fasting in Ramadan in patients with cardiac disease • Al Suwaidi J etal analysed 465 patients from various medical centers in the Gulf region. • one month before Ramadan, during Ramadan and one month after Ramadan and analyzed predictors of outcome. • found that 91.2% could fast and only 6.7% felt worse while fasting in Ramadan. Of the studied subjects, 82.8% were compliant with cardiac medications and 68.8% were compliant with dietary instructions. CONCLUSION: • The effects of fasting during Ramadan on stable patients with cardiac disease are minimal. Most patients with stable cardiac disease can fast. Cerebrovascular disease • Retrospective study over 5 years period- patients hospitalized in Isparta Province's hospitals between, 1991 -1995 with a diagnosis of stroke. • Patients admitted in Ramadan were compared to those admitted in the other months of the year. • Incidence of stroke in Ramadan and other months were 12.1 and 11.4 per 100,000 people, respectively which was statistically insignificant (P=0.82). • Retrospective study, reviewed a 13-year stroke database on Muslim patients who were hospitalised with stroke between 1991 - 2003 at Hamad General Hospital, Doha. • Patients admitted with stroke were compared in relation to the month of Ramadan, one month before, and one month after Ramadan. • 335 Muslim patients were admitted over a 13years period . • The incidence of stroke was ( 30,29,29 patients). • The clinical characteristics of such as age , gender, CVS risk factor profiles ,medications -no significant difference between the periods . • Conclusion ; fasting during Ramadan does not increase the frequency of hospitalisation for stroke. • No statistically significant difference between stroke rates in the Ramadan fasting month and other non-fasting months. Ramadan fasting and kidney transplantation • In healthy persons Ramadan fasting does not induce any abnormalities of urinary PH volume,osmolality,solute and electrolyte excretion. • Changes in serum urea , creatinine,sodium and potassium are usually insignificant. • With increasing number of renal transplants the question of ramadan fasting is being asked more frequently. • El-Wakil et al. performed a prospective study on 15 predialysis (CKD) patients who did fast during Ramadan. • The study showed that the change in GFR was not significantly different in CKD patients compared to the control group . • All CKD patients tolerated fasting without any new complaints and had no difficulties regarding timing or dosing of their medications. El-Wakil et al Saudi J Kidney Dis Transpl 18:349–354 Arganie et al-2003 24 patients All fast Stable renal transplant B. Einollahi et al2005 39 patients 20 fast 19 no fast Stable renal transplant B. Einollahi et al2009 82 patients 41 fasted 41 control no fast Patients with GFR >60 ml/min can fast Ramadan safely. Abdull et al-1998 23 patients 17 stable 6 Impaired RF Galib et al-2008 68 patients 35 Fast 33 no fast Said et al -2003 145 patients 71 fasted 74 no fast Boobes et al-2009 22 female All fast Cr < 300 mmol prospective study on 41 healthy kidney transplant recipient volunteers who choose to fast and 41 recipients who had not fasted during Ramadan (September–October 2007) at five transplant centers in Iran. • B. Einollahi et al. reported that GFR did not change significantly in kidney recipients with normal as well as impaired renal allograft function during Ramadan • No significant change in serum creatinine and GFR from before and after Ramadan in either the group that fasted or the group that had not fasted for equal to or more than 3 consecutive years. • No increase in acute complications, acute rejection or ATN during Ramadan. • No adverse effects on systolic and diastolic BP. • Ghalib et al. have published a prospective cohort study in renal transplant patients who fasted or who did not fast for three consecutive Ramadans. • 68 patients with renal transplant ,35 patients in a fasting study group and 33 in nonfasting control group There were no significant differences between the fasters and the nonfasters with regards to changes in GFR, mean arterial pressure and urinary protein excretion between baseline and the third Ramadan. • These studies demonstrate that fasting is safe among kidney transplant recipients with normal as well as mild to moderate impaired renal allograft function. • Patients with moderate to severe renal allograft dysfunction are discouraged fasting. Int Urol Nephrol (2009) Recommendations of the author • Compliance to drug intake and proper diet . • Fasting under medical supervision . • The timing of immunosuppressive agents should be divided between iftar and sohour • The dose of diuretics should be reduced to avoid dehydration. • sustained release formulations especially of anti-hypertensive drugs, can be given once a day before the pre-dawn (sohour) meal. • serum creatinine values should be closely monitored especially before, during and after Ramadan. • If patients develop high levels of creatinine, they should end the fast immediately. Peptic ulcer disease • There is a fall in gastric secretion during prolonged fasting and gastrointestinal tract movements occur every 2 h. The gallbladder empties one to three times every 4 h, less frequently than in the fed state. • Complications of ulcers in fasting patients have been reported • Incidence of duodenal ulcer perforation is relatively high in Ramadan among the people who are fasting. • History of dyspepsia in patients who are fasting is an important predisposing factor for duodenal ulcer perforation.* • Patients with complicated peptic ulcer may be advised against fasting *Z. Censur et al Indian Journal of Surgery. (July-August 2005) • Asymptomatic patients may try fasting . • If hyperacidity continues to be a problem take ranitidine or small dose PPI at Iftar and Sohour Effect of Ramadan fasting on Muslim patients with chronic liver diseases • Elnadry MH et al, studied a total of 202 patients with chronic liver disease • Fasting -103 (51%) and the non-fasting - 99 (49%) patients. • Dyspeptic symptoms in the fasting (53.4%) and (38.4%) the nonfasting group (p=0.032). • G.I. bleeding in the fasting group (17.5%) ,non-fasting (14.1%) • The bleeding due to o.v. was significantly higher in the non-fasting group (9.1%) compared to (1%) in the fasting group (p=0.004). • liver function in the fasting group showed non significant changes pre, during and post-Ramadan regarding in the chronic hepatites. • Fasting cirrhotic patients developed child class C in (13%) during and (32.6%) after Ramadan compared to (0%) before (p=0.001) Elnadry MH et al, J Egypt Soc Parasitol. 2011 Aug Diabetes and fasting Ramadan Guidelines • The Casablanca guidelines were the first international attempt to provide a consensus on the psychological and physiological aspects of Ramadan. • The Diabetes and Ramadan Advisory Board have provided international medical recommendations for Muslims with diabetes who fast during Ramadan Recommendations for management of diabetes during Ramadan. • Al-Arouj M, Bouguerra R, Buse J, et al • A working group for the American Diabetes Association have reviewed the literature on the risks of fasting during Ramadan and provided guidance on clinical assessment prior to fasting followed by recommendations on how best to manage patients with type 1 and type 2 diabetes . • Diabetes Care 2005-and an updated 2010 • First International Congress on Health and Ramadan. Jan. 19-22, 1994, Casablanca, Morocco • Second International Congress on Health and Ramadan. Dec. 1-3, 1997, Istanbul, Turkey. • Third international congress on health and Ramadan 2001 tahran,Iran. • 4.6% prevalence of diabetes worldwide. • DM prevalence in KSA 23.7% • (EPIDIAR) study - population-based Epidemiology of Diabetes and Ramadan 1422/2001 in 12,243 people with diabetes from 13 Islamic countries • Result- 43% of patients with type 1 diabetes and 79% of patients with type 2 diabetes fast during Ramadan. • Around 40–50 million people with diabetes worldwide fast during Ramadan. • Many patients with diabetes insist on fasting during Ramadan, creating a medical challenge for themselves and their physicians. • It is important that medical professionals be aware of potential risks that may be associated with fasting during Ramadan. PATHOPHYSIOLOGY OF FASTING • During fasting, circulating glucose levels tend to fall, leading to decreased secretion of insulin. • levels of glucagon and catecholamines rise, stimulating the breakdown of glycogen, while gluconeogenesis is augmented. • After 16–24 hours fasting, glycogen stores become depleted, and the low levels of circulating insulin allow increased fatty acid release from adipocytes. • Oxidation of fatty acids generates ketones that can be used as fuel by skeletal and cardiac muscle, liver, kidney, and adipose tissue, thus sparing glucose for continued utilization by brain and erythrocytes. DIABETES CARE, VOLUME 28, NUMBER 9, SEPTEMBER 2005 2305 In patients with type 1 diabetes • Glucagon and Epinephrine secretion may fail to increase in response to hypoglycemia. • During a prolonged fast in the absence of adequate insulin can lead to excessive glycogen breakdown and increased gluconeogenesis and ketogenesis leading to hyperglycemia and ketoacidosis. Patients with type 2 diabetes • a prolonged fast may lead to hyperglycemia depending on the extent of insulin resistance and/or deficiency. • ketoacidosis is uncommon. RISKS ASSOCIATED WITH FASTING IN PATIENTS WITH DIABETES • • • • Hypoglycemia. Hyperglycemia. Diabetic ketoacidosis. Dehydration and thrombosis. Hypoglycemia • (EPIDIAR) study showed a high rate of acute complications. • However, a few studies on this topic using relatively small groups of patients suggest that complication rates may not be significantly increased. • EPIDIAR study showed that fasting during Ramadan increased the risk of severe hypoglycemia (defined as hospitalization due to hypoglycemia) some 4.7-fold in patients with type 1 diabetes and 7.5-fold in patients with type 2 diabetes. • Severe hypoglycemia was more frequent in patients in whom the dosage of oral hypoglycemic agents or insulin were changed and in those who reported a significant change in their lifestyle. Hyperglycemia • EPIDIAR study showed a 5x increase in the incidence of severe hyperglycemia (requiring hospitalization) during Ramadan in patients with type 2 diabetes. • An approximate 3x increase in the incidence with or without ketoacidosis in patients with type 1 diabetes. • Hyperglycemia may have been due to excessive reduction in dosages of medications to prevent hypoglycemia. • Increase in food and/or sugar intake had significantly higher rates of severe hyperglycemia. Diabetic ketoacidosis • type 1 diabetes are at increased risk. • Particularly if they are grossly hyperglycemic before Ramadan. • The risk increase if excessive reduction of insulin dosages based on the assumption that food intake is reduced during the month of Ramadan. Dehydration and thrombosis • • • • In hot and humid climates hard physical labor with excessive perspiration Hyperglycemia can result in osmotic diuresis. Orthostatic hypotension especially in patients with preexisting autonomic neuropathy. • Increase in syncope,falls, injuries, and bone fractures. • Hypercoagulable state due to an increase in clotting factors, a decrease in endogenous anticoagulants, and impaired fibrinolysis. • Increased blood viscosity secondary to dehydration may enhance the risk of thrombosis. • Alghadyan AA from Saudi Arabia reported increased incidence of retinal vein occlusion in patients who fasted during Ramadan due to dehydration. • coronary events and stroke were not increased during Ramadan MANAGEMENT • Patients need to be aware of the associated risks. • Follow the recommendations of health care providers. • Frequent monitoring of glycemia • Nutrition-healthy balanced diet, simple CHO and avoid fatty high CHO food at sunset (Iftar) meal, eat complex CHO at sohour and to be as late as possible. • Exercise- avoid excessive physical activity particularly during the few hours before the sunset meal . • Tarawaih prayer is considered as part of the daily exercise program. • Breaking the fast - must always end the fast if hypoglycemia blood glucose of 60 mg/dl. - if blood glucose reaches 70 mg/dl in the first few hours after the start of the fast, especially if insulin, sulfonylurea drugs, or meglitinide are taken with sohour. • if blood glucose exceeds 300 mg/dl. Medical assessment – - 1–2 months before Ramadan. -control of their glycemia,blood pressure, and lipids. -necessary changes in their diet or medication regimen should be made . Ramadan-focused structured diabetes education • Many health care professionals are unable to give the appropriate medical advice due to lack of knowledge about the optimum management of diabetes while fasting. • often people with diabetes feel that there is lack of harmony between the medical and the religious advice they receive. Ramadan educational program should ideally include three components: 1. An awareness campaign aimed at people with diabetes, health care professionals, the religious and community leaders as well as the general public. 2. Ramadan-focused structured education for health care professionals 3. Ramadan-focused structured education for people with diabetes. • structured education program, was conducted in 2007 in the U.K. for a group of 111 people with type 2 diabetes. • excluded people treated with insulin, secretagogues were used in over 90% of the people. • Individualized medication dose adjustments were suggested to all patients. • Compared with a control group who did not participate in the Ramadan-focused diabetes education • Those who received education exhibited a nearly 50% reduction in hypoglycemic event rates despite fasting, whereas those in the control group had experienced a 4x increase in the rate of hypoglycemic events from baseline during fasting. • The group that received structured education lost a small amount of weight compared to weight gain in the control group . Categories of risks in patients with type 1 or type 2 diabetes who fast during Ramadan Very high risk • • • • • • • • • • • Severe hypoglycemia within the last 3 months prior to Ramadan Patient with a history of recurrent hypoglycemia Patients with hypoglycemia unawareness Patients with sustained poor glycemic control Ketoacidosis within the last 3 months prior to Ramadan Type 1 diabetes Acute illness Hyperosmolar hyperglycemic coma within the previous 3 months Patients who perform intense physical labor Pregnancy Patients on chronic dialysis High risk • Patients with moderate hyperglycemia (average blood glucose between 150 and 300 mg/dl • A1C 7.5–9.0%) • Patients with renal insufficiency • Patients with advanced macrovascular complications • People living alone that are treated with insulin or sulfonylureas • Patients living alone • Patients with comorbid conditions that present additional risk factors • Old age with ill health • Drugs that may affect mentation Moderate risk • Well-controlled patients treated with shortacting insulin secretagogues such as repaglinide or nateglinide Low risk • Well-controlled patients treated with diet alone, metformin, or a thiazolidinedione who are otherwise healthy Management of patients with type 1 diabetes • Fasting at Ramadan carries a very high risk . • Especially in: poorly controlled patients ,those with limited access to medical care, hypoglycemic unawareness, unstable glycemic control, or recurrent hospitalizations, patients unwilling or unable to monitor their blood glucose levels several times daily. • Insulin regimens recommended represent the collective clinical opinion and many observational and/or interventional studies . • Glycemic control at near-normal levels requires - use of multiple daily insulin injections (three or more) or - continuous subcutaneous insulin infusion through pump therapy. • Close monitoring and frequent insulin dose adjustments is required. • the basal-bolus regimen is the preferred protocol of management. • It is safer, with fewer episodes of hyper- and hypoglycemia. • The use of once- or twice-daily injections of intermediate or long-acting insulin along with premeal rapid-acting insulin. Suggested insulin regimen in patients with type 1 diabetes who wish to fast during the month of Ramadan* • glargine and aspart or lispro 70% of the pre-Ramadan insulin dose divided as : 60% - 1 glargine dose in the evening and 40% as ultra-short-acting insulin (aspart or lispro) divided in 2 doses, 1 at Suhour and 1 at Iftar. Regular insulin should be used at Iftar instead of an ultra-short-acting insulin if snack is to be taken in the hours after the sunset meal. * A. Kobeissy et al Clinical Therapeutics/Volume 30, Number 8,2008 • Ultralente and regular insulin 85% of the pre-Ramadan dose may be divided as 70% Ultralente and 30% regular insulin, both given in 2 doses, 1 at Suhour and 1 at Iftar. • 70/30 premixed insulin 100% of the pre-Ramadan morning dose may be given at Iftar and 50% of the usual evening dose at Suhour • NPH insulin may be associated with hypoglycemic events during prolonged fasting, as its peak effect usually occurs between 6 and 10 hours after the time of injection. • a long-acting insulin (eg, insulin glargine) that lacks the peak effect would be more appropriate Patients on insulin infusion (pump) • observational study - 49 patients type 1 diabetes patients on insulin pumps during Ramadan 2008 (29 days). • All patients were stable on their insulin pump and were deemed to be fully educated in insulin pump self-management and carbohydrate counting for adjusting their bolus insulin. • 30 patients (61.2%) fasted the whole month with no problems • 19 (38.7%) fasted between 23 and 28 days . • Nearly half of the patients decreased their basal insulin rate by 5-50% • Seventeen patients had hypoglycemia necessitating breaking their fast • Fasting was broken on 55 out of 1,450 potential fasting days (3.8%). • Unusual hyperglycemia was reported in nine patients (18%) • Hypoglycemia can be aborted, reduced, prevented, and even more readily treated in pump-treated patients by timely downward adjustments or even totally stopping of insulin delivery from the pump. • Most will need to reduce their basal infusion rate whilst increasing the bolus doses to cover the sohour and Iftar meals. Management of patients with type 2 diabetes Diet-controlled patients • Distributing calories over two to three smaller meals during the nonfasting interval may help prevent excessive postprandial hyperglycemia. Patients treated with oral agents. • agents that act by increasing insulin sensitivity are associated with a significantly lower risk of hypoglycemia than compounds that act by increasing insulin secretion. Metformin. • possibility of severe hypoglycemia is minimal. • dose modefied - two-thirds of the total daily dose with the Iftar meal and the other third before the Sohour meal. Glitazones • require 2–4 weeks to exert antihyperglycemic effects. • cannot be quickly substituted for agents associated with hypoglycemia during periods of fasting. Sulfonylureas. • Severe or fatal hypoglycemia is a relatively rare complication • sulfonylureas glyburide (glibenclamide) and gliclazide MR have played a central role in the long-term outcome studies UKPDS and ADVANCE • both of which demonstrated microvascular benefits and at least trends toward improvements in cardiovascular disease without evidence of excess mortality • Zargar et al used gliclazide MR 60 mg as monotherapy during the month of Ramadan in 136 non-obese males. • No alteration of previously well-controlled diabetes, no weight gain and, importantly, few hypoglycemic event. • Three studies have shown glimepiride to be effective and safe during Ramadan. • Bakiner et al reported that meal-time repaglinide three times a day plus single-dose insulin glargine was safe (no hypoglycemia, no change in glycemic control or weight gain) for low-risk type 2 diabetic individuals who insisted on fasting during Ramadan. Incritins Hormones secreted by enteroendocrine cells postprandially to regulate glucose homeostasis • Glucagon-like peptide-1 (GLP-1). exenatide, liraglutide (GLP-1 memetics) • Glucose-dependent insulinotropic polypeptide sitagliptin, vildagliptin [dipeptidyl peptidase (DPP-4, inhibitor). GLP1 memetics • No published reports on the use of these agents during Ramadan • LEAD-6 trial, liraglutide once a day provided greater improvements in glycemic control than did exenatide twice a day, and with less incidence of hypoglycemia ,less nausea, better glycemic control (1.8% reduction in HbA1c) and weight loss of around 3 kg. DPP-4 inhibitors • Report from northwest London, Muslim diabetic individuals on 2 g daily metformin during Ramadan. • randomized to the addition of either vildagliptin 50 mg daily (26 individuals) or gliclazide 160 mg twice daily (26 individuals). • one hypoglycemic event was recorded in 2 patients receiving vildagliptin and 16 patients receiving gliclazide. D. Devendra et al Int J Clin Pract, October 2009 • similar reductions in HbA1c and a small, but insignificant, increase in weight. • DPP-4 inhibitors provide a safe alternative therapeutic option during Ramadan. Conclusion • Since over 400 million people fast each year during the month of Ramadan • Further scientific research on the medical and healthrelated aspects of Ramadan fasting is needed. • Health personnel practicing in Muslim countries, as well as those caring for Muslims in various parts of the world need to be fully aware of the physiological alterations occurring during Ramadan. • The effects of Islamic fasting on various diseases and the pharmacodynamics of different medications during the month of Ramadan. • Most patients with stable cardiac disease can fast. There is no increase incidence of acute coronary events or CHF hospitalisation • Ther is no increase in the stroke incident compared to other monthe of the year • Patient with allograft renal transplant with normal or mild renal impairment can fast Ramadan under supervision • Diabetic patient need to be aware of the associated risks, and to follow the recommendations of health care providers so that they a safe fasting. نز َل ِفي ِه ْٱلقُ ْر ُ اس قال تعالىَ { : ض َ آن ُهدًى لّلنَّ ِ ش ْه ُر َر َم َ ان ٱلَّ ِذى أ ُ ِ ش ِهدَ ِمن ُك ُم ال َّ ص ْمهُ َوبَ ِيّنَ ٰـ ٍ ان فَ َمن َ ش ْه َر فَ ْليَ ُ ت ِ ّم َن ْٱل ُهدَ ٰى َو ْٱلفُ ْرقَ ِ ٱّللُ ِب ُك ُم َو َمن َك َ سفَ ٍر فَ ِعدَّة ٌ ّم ْن أَي ٍَّام أُخ ََر يُ ِريدُ َّ ان َم ِري ً ضا أ َ ْو َ علَ ٰى َ ٱّلل َهدَا ُك ْم ْٱليُ ْس َر َوالَ يُ ِريدُ ِب ُك ُم ْٱلعُ ْس َر َو ِلت ُ ْك ِملُواْ ْٱل ِعدَّة َ َو ِلت ُ َكب ُّرواْ ََّ علَ ٰى َما َولَعَلَّ ُك ْم ت َ ْش ُك ُر َ ون} [البقرةَ ] 185 :