It is estimated that there are 1.1–1.5 billion Muslims worldwide, comprising 18–25% of the world population (1,2). Fasting during Ramadan, a holy month of Islam, is an obligatory duty for all healthy ....... Muslims. An ∼4.6% prevalence of diabetes worldwide (3) coupled with the results of the population-based Epidemiology of Diabetes and Ramadan 1422/2001 (EPIDIAR) study, which showed (in 12,243 people with diabetes from 13 Islamic countries) that ∼43% of patients with type 1 diabetes and ∼79% of patients with type 2 diabetes fast during Ramadan (4), lead to the estimation that some 40–50 million people with diabetes worldwide fast during Ramadan.
Ramadan is a lunar-based month, and its duration varies between 29 and 30 days. Its timing changes with respect to seasons. Depending on the geographical location and season, the duration of the daily fast may range from a few to more than 20 h. Muslims who fast during Ramadan must abstain from eating, drinking, use of oral medications, and smoking from predawn to after sunset; however, there are no restrictions on food or fluid intake between sunset and dawn. Most people consume two meals per day during this month, one after sunset, referred to in Arabic as Iftar (breaking of the fast meal), and the other before dawn, referred to as Suhur (predawn). Fasting is not meant to create excessive hardship on the Muslim individual. The Koran specifically exempts the sick from the duty of fasting (Holy Koran, Al-Bakarah, 183–185), especially if fasting might lead to harmful consequences for the individual. Patients with diabetes fall under this category because their chronic metabolic disorder may place them at high risk for various complications if the pattern and amount of their meal and fluid intake is markedly altered. This exemption represents more than a simple permission not to fast; the Prophet Mohammad said, “God likes his permission to be fulfilled, as he likes his will to be executed.” Nevertheless, many patients with diabetes insist on fasting during Ramadan, thereby creating a medical challenge for themselves and their physicians. It is therefore important that medical professionals be aware of potential risks that may be associated with fasting during Ramadan. This familiarity and knowledge is as important in Indonesia, Pakistan, and the Middle East as it is in Europe, North America, New Zealand, and Australia.
The medical ramifications of fasting among patients with diabetes are largely unknown. Due to the limited information available from prospective or retrospective studies on the effects of fasting during Ramadan, a group of endocrinologists and diabetologists from a number of Muslim and non-Muslim countries met to exchange information and opinions and to propose a set of recommendations. Although recommendations for management of diabetes in patients who elect to fast during Ramadan were proposed in 1995 at a conference in Casablanca (5), the present effort was prompted by data from the EPIDIAR study (4) showing that fasting is quite common among Muslims with diabetes and by the increasing awareness that this represents a global medical issue. The purposes of the recommendations that follow are threefold: 1) to invite an open dialogue on this important topic, 2) to offer a set of medical opinions and suggestions, and 3) to identify topics of research needed to answer important medical questions regarding fasting during Ramadan.
In this document, we avoid use of the terms “indications” or “contraindications” for fasting because fasting is a religious issue for which patients make their own decision after receiving appropriate advice from religious teachings and from their own health care providers. However, we emphasize that fasting, especially among patients with type 1 diabetes with poor glycemic control, is associated with multiple risks. In addition to highlighting the potential risks, we provide suggestions on how to manage the patients with diabetes who decide to fast during Ramadan.
PATHOPHYSIOLOGY OF FASTING
Insulin secretion in healthy individuals is stimulated with feeding, which promotes the storage of glucose in liver and muscle as glycogen. In contrast, during fasting, circulating glucose levels tend to fall, leading to decreased secretion of insulin. At the same time, levels of glucagon and catecholamines rise, stimulating the breakdown of glycogen, while gluconeogenesis is augmented (6). As fasting becomes protracted for more than several hours, 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.
In individuals without diabetes, the processes described above are regulated by a delicate balance between circulating levels of insulin and counterregulatory hormones that help maintain glucose concentrations in the physiological range. In patients with diabetes, however, insulin secretion is perturbed by the underlying pathophysiology and often by pharmacological agents designed to enhance or supplement insulin secretion. In patients with type 1 diabetes, glucagon secretion may fail to increase appropriately in response to hypoglycemia. Epinephrine secretion is also defective in some patients with type 1 diabetes due to a combination of autonomic neuropathy and defects associated with recurrent hypoglycemia (6). In patients with severe insulin deficiency, 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 may suffer similar perturbations in response to a prolonged fast; however, ketoacidosis is uncommon, and the severity of hyperglycemia depends on the extent of insulin resistance and/or deficiency.
RISKS ASSOCIATED WITH FASTING IN PATIENTS WITH DIABETES
Fasting during Ramadan has been uniformly discouraged by the medical profession for patients with diabetes. In keeping with this, a large epidemiological study conducted in 13 Islamic countries on 12,243 individuals with diabetes who fasted during Ramadan showed a high rate of acute complications (4). However, a few studies on this topic using relatively small groups of patients suggest that complication rates may not be significantly increased (7–11). In Table 1, we outline some of the major potential complications associated with fasting in patients with diabetes and briefly discuss them below.
Hypoglycemia
Decreased food intake is a well-known risk factor for the development of hypoglycemia. Results of the Diabetes Control and Complications Trial (DCCT) showed a threefold increase in the risk of severe hypoglycemia in patients who were in the intensively treated group and had an average HbA1c (A1C) value of 7.0% (12). It has been estimated that hypoglycemia accounts for 2–4% of mortality in patients with type 1 diabetes (13). There are no reliable estimates concerning the contribution of hypoglycemia to mortality in type 2 diabetes; however, it is felt that hypoglycemia is an infrequent cause of death in this group of patients. Rates of hypoglycemia are some several-fold lower in patients with type 2 compared with type 1 diabetes (4), with rates being even lower in patients with type 2 diabetes treated with oral agents (14).
The effect of fasting during Ramadan on rates of hypoglycemia in patients with diabetes is not known with certainty. The largest dataset is the recent EPIDIAR study (4), which 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 (from 3 to 14 events · 100 people−1 · month−1) and ∼7.5-fold in patients with type 2 diabetes (from 0.4 to 3 events · 100 people−1 · month−1). The incidence of severe hypoglycemia was probably underestimated in this study, since events requiring assistance from a third party without the need for hospitalization were not included. Furthermore, although the average A1C at the beginning of Ramadan was not given, it is unlikely that the patients in this study were in good glycemic control. 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 (4).
Hyperglycemia
Long-term morbidity and mortality studies in people with diabetes, such as the DCCT and the UKPDS (U.K. Prospective Diabetes Study), demonstrated the link among hyperglycemia, microvascular complications, and possibly macrovascular complications (12,15). However, there is no information linking repeated yearly episodes of short-term hyperglycemia (e.g., 4-week duration) and diabetes-related complications. Control of glycemia in patients with diabetes who fasted during Ramadan has been reported to deteriorate, improve, or show no change (7–11). The extensive EPIDIAR study showed a fivefold increase in the incidence of severe hyperglycemia (requiring hospitalization) during Ramadan in patients with type 2 diabetes (from 1 to 5 events · 100 people−1 · month−1) and an approximate threefold increase in the incidence of severe hyperglycemia with or without ketoacidosis in patients with type 1 diabetes (from 5 to 17 events · 100 people−1 · month−1) (4). Hyperglycemia may have been due to excessive reduction in dosages of medications to prevent hypoglycemia. Patients who reported an increase in food and/or sugar intake had significantly higher rates of severe hyperglycemia (4).
Diabetic ketoacidosis
Patients with diabetes, especially those with type 1 diabetes, who fast during Ramadan are at increased risk for development of diabetic ketoacidosis, particularly if they are grossly hyperglycemic before Ramadan (4). In addition, the risk for diabetic ketoacidosis may be further increased due to excessive reduction of insulin dosages based on the assumption that food intake is reduced during the month.
Dehydration and thrombosis
Limitation of fluid intake during the fast, especially if prolonged, is a cause of dehydration. The dehydration may become severe in hot and humid climates and among individuals who perform hard physical labor, all conditions that result in excessive perspiration. In addition, hyperglycemia can result in osmotic diuresis and contribute to volume and electrolyte depletion. Orthostatic hypotension may develop, especially in patients with preexisting autonomic neuropathy. Syncope, falls, injuries, and bone fractures may result from hypovolemia and the associated hypotension. In addition, contraction of the intravascular space can contribute to a hypercoagulable state.
Patients with diabetes exhibit a hypercoagulable state due to an increase in clotting factors, a decrease in endogenous anticoagulants, and impaired fibrinolysis (16). Increased blood viscosity secondary to dehydration may enhance the risk of thrombosis. A report from Saudi Arabia suggested an increased incidence of retinal vein occlusion in patients who fasted during Ramadan (17). However, hospitalizations due to coronary events or stroke were not increased during Ramadan (18,19). There are no data concerning the effect of fasting on mortality in patients with or without diabetes.
MANAGEMENT
It is worth reemphasizing that fasting for patients with diabetes represents an important personal decision that should be made in light of guidelines for religious exemptions and after careful consideration of the associated risks following ample discussion with the treating physician. Most often, the recommendation will be to not undertake fasting. However, patients who insist on fasting need to be aware of the associated risks and be ready to adhere to the recommendations of their health care providers to achieve a safer fasting experience. Patients may be at higher or lower risk for fasting-related complications depending on the number and extent of their risk factors. Conditions associated with “very high,” “high,” “moderate,” and “low” risk for adverse events in patients with type 1 or type 2 diabetes who decide to fast during Ramadan are listed in Table 2. This classification is based largely on expert opinion and not on scientific data derived from clinical studies.
I. General considerations
Several important issues deserve special attention.
Individualization.
Perhaps the most crucial issue is the realization that care must be highly individualized and that the management plan will differ for each specific patient.
Frequent monitoring of glycemia.
It is essential that patients have the means to monitor their blood glucose levels multiple times daily. This is especially critical in patients with type 1 diabetes and in patients with type 2 diabetes who require insulin.
Nutrition.
The diet during Ramadan should not differ significantly from a healthy and balanced diet. It should aim at maintaining a constant body mass. In most studies, 50–60% of individuals who fast maintain their body weight during the month, while 20–25% either gain or lose weight (4); occasionally, the weight loss may be excessive (>3 kg). The common practice of ingesting large amounts of foods rich in carbohydrate and fat, especially at the sunset meal, should be avoided. Because of the delay in digestion and absorption, ingestion of foods containing “complex” carbohydrates may be advisable at the predawn meal, while foods with more simple carbohydrates may be more appropriate at the sunset meal. It is also recommended that fluid intake be increased during nonfasting hours and that the predawn meal be taken as late as possible before the start of the daily fast.
Exercise.
Normal levels of physical activity may be maintained. However, excessive physical activity may lead to higher risk of hypoglycemia and should be avoided, particularly during the few hours before the sunset meal. If Tarawaih prayer (multiple prayers after the sunset meal) is performed, then it should be considered a part of the daily exercise program. In some patients with poorly controlled type 1 diabetes, exercise may lead to extreme hyperglycemia.
Breaking the fast.
All patients should understand that they must always and immediately end their fast if hypoglycemia (blood glucose of
Ramadan is a lunar-based month, and its duration varies between 29 and 30 days. Its timing changes with respect to seasons. Depending on the geographical location and season, the duration of the daily fast may range from a few to more than 20 h. Muslims who fast during Ramadan must abstain from eating, drinking, use of oral medications, and smoking from predawn to after sunset; however, there are no restrictions on food or fluid intake between sunset and dawn. Most people consume two meals per day during this month, one after sunset, referred to in Arabic as Iftar (breaking of the fast meal), and the other before dawn, referred to as Suhur (predawn). Fasting is not meant to create excessive hardship on the Muslim individual. The Koran specifically exempts the sick from the duty of fasting (Holy Koran, Al-Bakarah, 183–185), especially if fasting might lead to harmful consequences for the individual. Patients with diabetes fall under this category because their chronic metabolic disorder may place them at high risk for various complications if the pattern and amount of their meal and fluid intake is markedly altered. This exemption represents more than a simple permission not to fast; the Prophet Mohammad said, “God likes his permission to be fulfilled, as he likes his will to be executed.” Nevertheless, many patients with diabetes insist on fasting during Ramadan, thereby creating a medical challenge for themselves and their physicians. It is therefore important that medical professionals be aware of potential risks that may be associated with fasting during Ramadan. This familiarity and knowledge is as important in Indonesia, Pakistan, and the Middle East as it is in Europe, North America, New Zealand, and Australia.
The medical ramifications of fasting among patients with diabetes are largely unknown. Due to the limited information available from prospective or retrospective studies on the effects of fasting during Ramadan, a group of endocrinologists and diabetologists from a number of Muslim and non-Muslim countries met to exchange information and opinions and to propose a set of recommendations. Although recommendations for management of diabetes in patients who elect to fast during Ramadan were proposed in 1995 at a conference in Casablanca (5), the present effort was prompted by data from the EPIDIAR study (4) showing that fasting is quite common among Muslims with diabetes and by the increasing awareness that this represents a global medical issue. The purposes of the recommendations that follow are threefold: 1) to invite an open dialogue on this important topic, 2) to offer a set of medical opinions and suggestions, and 3) to identify topics of research needed to answer important medical questions regarding fasting during Ramadan.
In this document, we avoid use of the terms “indications” or “contraindications” for fasting because fasting is a religious issue for which patients make their own decision after receiving appropriate advice from religious teachings and from their own health care providers. However, we emphasize that fasting, especially among patients with type 1 diabetes with poor glycemic control, is associated with multiple risks. In addition to highlighting the potential risks, we provide suggestions on how to manage the patients with diabetes who decide to fast during Ramadan.
PATHOPHYSIOLOGY OF FASTING
Insulin secretion in healthy individuals is stimulated with feeding, which promotes the storage of glucose in liver and muscle as glycogen. In contrast, during fasting, circulating glucose levels tend to fall, leading to decreased secretion of insulin. At the same time, levels of glucagon and catecholamines rise, stimulating the breakdown of glycogen, while gluconeogenesis is augmented (6). As fasting becomes protracted for more than several hours, 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.
In individuals without diabetes, the processes described above are regulated by a delicate balance between circulating levels of insulin and counterregulatory hormones that help maintain glucose concentrations in the physiological range. In patients with diabetes, however, insulin secretion is perturbed by the underlying pathophysiology and often by pharmacological agents designed to enhance or supplement insulin secretion. In patients with type 1 diabetes, glucagon secretion may fail to increase appropriately in response to hypoglycemia. Epinephrine secretion is also defective in some patients with type 1 diabetes due to a combination of autonomic neuropathy and defects associated with recurrent hypoglycemia (6). In patients with severe insulin deficiency, 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 may suffer similar perturbations in response to a prolonged fast; however, ketoacidosis is uncommon, and the severity of hyperglycemia depends on the extent of insulin resistance and/or deficiency.
RISKS ASSOCIATED WITH FASTING IN PATIENTS WITH DIABETES
Fasting during Ramadan has been uniformly discouraged by the medical profession for patients with diabetes. In keeping with this, a large epidemiological study conducted in 13 Islamic countries on 12,243 individuals with diabetes who fasted during Ramadan showed a high rate of acute complications (4). However, a few studies on this topic using relatively small groups of patients suggest that complication rates may not be significantly increased (7–11). In Table 1, we outline some of the major potential complications associated with fasting in patients with diabetes and briefly discuss them below.
Hypoglycemia
Decreased food intake is a well-known risk factor for the development of hypoglycemia. Results of the Diabetes Control and Complications Trial (DCCT) showed a threefold increase in the risk of severe hypoglycemia in patients who were in the intensively treated group and had an average HbA1c (A1C) value of 7.0% (12). It has been estimated that hypoglycemia accounts for 2–4% of mortality in patients with type 1 diabetes (13). There are no reliable estimates concerning the contribution of hypoglycemia to mortality in type 2 diabetes; however, it is felt that hypoglycemia is an infrequent cause of death in this group of patients. Rates of hypoglycemia are some several-fold lower in patients with type 2 compared with type 1 diabetes (4), with rates being even lower in patients with type 2 diabetes treated with oral agents (14).
The effect of fasting during Ramadan on rates of hypoglycemia in patients with diabetes is not known with certainty. The largest dataset is the recent EPIDIAR study (4), which 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 (from 3 to 14 events · 100 people−1 · month−1) and ∼7.5-fold in patients with type 2 diabetes (from 0.4 to 3 events · 100 people−1 · month−1). The incidence of severe hypoglycemia was probably underestimated in this study, since events requiring assistance from a third party without the need for hospitalization were not included. Furthermore, although the average A1C at the beginning of Ramadan was not given, it is unlikely that the patients in this study were in good glycemic control. 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 (4).
Hyperglycemia
Long-term morbidity and mortality studies in people with diabetes, such as the DCCT and the UKPDS (U.K. Prospective Diabetes Study), demonstrated the link among hyperglycemia, microvascular complications, and possibly macrovascular complications (12,15). However, there is no information linking repeated yearly episodes of short-term hyperglycemia (e.g., 4-week duration) and diabetes-related complications. Control of glycemia in patients with diabetes who fasted during Ramadan has been reported to deteriorate, improve, or show no change (7–11). The extensive EPIDIAR study showed a fivefold increase in the incidence of severe hyperglycemia (requiring hospitalization) during Ramadan in patients with type 2 diabetes (from 1 to 5 events · 100 people−1 · month−1) and an approximate threefold increase in the incidence of severe hyperglycemia with or without ketoacidosis in patients with type 1 diabetes (from 5 to 17 events · 100 people−1 · month−1) (4). Hyperglycemia may have been due to excessive reduction in dosages of medications to prevent hypoglycemia. Patients who reported an increase in food and/or sugar intake had significantly higher rates of severe hyperglycemia (4).
Diabetic ketoacidosis
Patients with diabetes, especially those with type 1 diabetes, who fast during Ramadan are at increased risk for development of diabetic ketoacidosis, particularly if they are grossly hyperglycemic before Ramadan (4). In addition, the risk for diabetic ketoacidosis may be further increased due to excessive reduction of insulin dosages based on the assumption that food intake is reduced during the month.
Dehydration and thrombosis
Limitation of fluid intake during the fast, especially if prolonged, is a cause of dehydration. The dehydration may become severe in hot and humid climates and among individuals who perform hard physical labor, all conditions that result in excessive perspiration. In addition, hyperglycemia can result in osmotic diuresis and contribute to volume and electrolyte depletion. Orthostatic hypotension may develop, especially in patients with preexisting autonomic neuropathy. Syncope, falls, injuries, and bone fractures may result from hypovolemia and the associated hypotension. In addition, contraction of the intravascular space can contribute to a hypercoagulable state.
Patients with diabetes exhibit a hypercoagulable state due to an increase in clotting factors, a decrease in endogenous anticoagulants, and impaired fibrinolysis (16). Increased blood viscosity secondary to dehydration may enhance the risk of thrombosis. A report from Saudi Arabia suggested an increased incidence of retinal vein occlusion in patients who fasted during Ramadan (17). However, hospitalizations due to coronary events or stroke were not increased during Ramadan (18,19). There are no data concerning the effect of fasting on mortality in patients with or without diabetes.
MANAGEMENT
It is worth reemphasizing that fasting for patients with diabetes represents an important personal decision that should be made in light of guidelines for religious exemptions and after careful consideration of the associated risks following ample discussion with the treating physician. Most often, the recommendation will be to not undertake fasting. However, patients who insist on fasting need to be aware of the associated risks and be ready to adhere to the recommendations of their health care providers to achieve a safer fasting experience. Patients may be at higher or lower risk for fasting-related complications depending on the number and extent of their risk factors. Conditions associated with “very high,” “high,” “moderate,” and “low” risk for adverse events in patients with type 1 or type 2 diabetes who decide to fast during Ramadan are listed in Table 2. This classification is based largely on expert opinion and not on scientific data derived from clinical studies.
I. General considerations
Several important issues deserve special attention.
Individualization.
Perhaps the most crucial issue is the realization that care must be highly individualized and that the management plan will differ for each specific patient.
Frequent monitoring of glycemia.
It is essential that patients have the means to monitor their blood glucose levels multiple times daily. This is especially critical in patients with type 1 diabetes and in patients with type 2 diabetes who require insulin.
Nutrition.
The diet during Ramadan should not differ significantly from a healthy and balanced diet. It should aim at maintaining a constant body mass. In most studies, 50–60% of individuals who fast maintain their body weight during the month, while 20–25% either gain or lose weight (4); occasionally, the weight loss may be excessive (>3 kg). The common practice of ingesting large amounts of foods rich in carbohydrate and fat, especially at the sunset meal, should be avoided. Because of the delay in digestion and absorption, ingestion of foods containing “complex” carbohydrates may be advisable at the predawn meal, while foods with more simple carbohydrates may be more appropriate at the sunset meal. It is also recommended that fluid intake be increased during nonfasting hours and that the predawn meal be taken as late as possible before the start of the daily fast.
Exercise.
Normal levels of physical activity may be maintained. However, excessive physical activity may lead to higher risk of hypoglycemia and should be avoided, particularly during the few hours before the sunset meal. If Tarawaih prayer (multiple prayers after the sunset meal) is performed, then it should be considered a part of the daily exercise program. In some patients with poorly controlled type 1 diabetes, exercise may lead to extreme hyperglycemia.
Breaking the fast.
All patients should understand that they must always and immediately end their fast if hypoglycemia (blood glucose of