ISPAD Clinical Practice Consensus Guidelines 2022: Ramadan and other religious fasting by young people with diabetes.

Abstract

Fasting is advised, with variable rules, in healthy adults and adolescents in different religions. A common purpose of fasting in these religions is to gain self-restraint, arouse spiritual consciousness, and better understand the plight of the poor and hungry. In this section, general rules and religious guidance on observing and breaking fasting in different religions are given, with emphasis on potential effects on health and glycemic outcomes in children and adolescents with T1D who choose to fast. Ramadan fasting is one of the five pillars of Islam and is obligatory for all healthy adult and adolescent Muslims from the time of completing puberty.1 As per the Islamic rules and guidance from Sunnah (the way of prophet Mohamed), an individual becomes subject to Shari'a rulings that apply when specific features of puberty are attained. Approximately 1.9 billion Muslims celebrate the ninth month of the Hijri (lunar) calendar notable for Ramadan fasting all over the world.2 The Epidemiology of Diabetes and Ramadan (EPIDIAR), a population-based study conducted in 13 countries and involving almost 13,000 adults with diabetes, showed that 78.7% of individuals with type 2 diabetes (T2D) and 42.8% of those with T1D fast for at least for 15 days during Ramadan. Saudi Arabia had the maximum number of individuals with T1D who chose to fast.3 The duration of fasting during Ramadan varies based on geographical location and season but is mandated to be between dawn and dusk. During this period, people who fast abstain from eating, drinking, use of oral medications, and smoking. There are no restrictions on food or fluid intake between dusk and dawn.1, 4 Fasting during Ramadan is not intended to bring excessive difficulty or cause any adverse effect to the individual. Islam has allowed many categories of people to be exempted from fasting; for example, menstruating, pregnant or breastfeeding women, prepubertal children, the elderly, individuals with any acute or chronic illness in whom fasting would be detrimental to health, individuals with an intellectual disability, or individuals who are traveling.1 These principles formed the basis of all the consensus statements by several groups.5-7 The provisions of al-Fitr (i.e., Not to observe the fast) in Ramadan apply if there is any sickness, according to the Almighty saying: “Whoever of you is sick or on a journey, and some of the other days, and on those who support him, ransom poor food.”1 Therefore, if a person fasts and experiences harm or serious hardship while fasting, he/she may be committing a sin.4 Various beliefs exist regarding diabetes management practices during Ramadan. In a study of fasting during Ramadan that included 800 individuals with diabetes, 67% indicated that pricking the skin to measure BGLs breaks the fast.8 Such a belief might endanger individuals with diabetes and predispose them to acute complications. Medical counseling and liaison with Islamic scholars can help correct wrong interpretation as well as understanding and ensure safer fasting. Although some experts would consider fasting, particularly during Ramadan, a practice at high risk for metabolic deterioration, recent studies have demonstrated that individuals with T1D can fast safely during Ramadan, provided they comply with the fasting-focused management plan and are under close professional supervision.6, 9 The Eastern Christian Orthodox Church is the second-largest Christian church, with ~300 million members.10 Orthodox Fasting (OF) is a basic and traditional component of the religion, practiced by a large proportion of the Orthodox population.11 OF includes three main fasting periods: 40 days prior to Christmas, 48 days prior to Easter, 14 days prior to Assumption, along with the fasting period prior to the feast of the Holy Apostles (lasting from 0 to 30 days depending on Easter feast), three other daily feasts (January 5, August 29, September 14), as well as every Wednesday and Friday. Individuals 18–59 years old are expected to fast during these periods. OF is a kind of periodical diet which recommends abstaining from meat, dairy products and eggs for about 180 days annually, and also abstaining from fish for 155 days. The diet during periods of fasting is characterized by increased consumption of cereals, legumes, fruits, vegetables, nuts and seafood. For this reason, it may be considered as a vegetarian dietary pattern, where fasting and non-fasting periods alternate, sharing common features with the classical Mediterranean Diet.11, 12 Studies on OF followers conducted in three different countries (Greece, United States, and Egypt), reported low total energy intake, low fat (total, saturated and trans), low animal and high vegetable protein intake, high complex carbohydrate and fiber intake, high vitamin C, folate and magnesium intake, low calcium and vitamin D intake during different fasting periods.13, 14 The OF meal plan tends to be high in carbohydrate content. Thus, it is advisable for people with T1D to choose carbohydrates with a low glycemic index, and consume them in combination with fiber, proteins (legumes, seafood) or fats (olive oil). Rye, barley, oats, brown rice, quinoa or amaranth are also suitable.15 Although data on the effect of OF diet on metabolic health are heterogenous, a potential benefit on lipid profile has been suggested, whereas there are no data on the effects on cardiovascular and musculoskeletal outcomes. Negative aspects of OF, primarily attributed to dietary limitations of specific vitamins (D and B12) and minerals (calcium and iron), should not be ignored, and relevant guidance might be provided to people following OF by health care professionals.13 Yom Kippur fasting is a major fast and the holiest day in the Jewish religion and calendar.16 It is obligatory for all healthy adult and adolescent Jews from the age of 13 years in males and 12 years in females. All observant and most non-observant Jews practice this 25 h long fasting. It starts at dusk (end of the ninth of Tishrei—first month of the Jewish lunar year) and ends on the following day (10th of Tishrei) at sunset.16 The activity during this fast involves mostly prayer and soul searching within synagogues. Jewish law includes five other days of fasting between dawn and dusk, and these are mostly practiced only by observant Jews. During fasting, Jews abstain from eating, drinking, and smoking. Fasting is not intended to cause any adverse effect to the individual.17 Jewish law allows many categories of people to be exempted from fasting; for example, prepubertal children, women in and around delivery days, individuals with illnesses in whom fasting may be detrimental to health, and individuals with an intellectual disability.17 Jewish law defines an intermediate state where people who need to break their fast due to health reasons can intermittently eat small portions of 30 g in line with a scheduled time plan.16 Various approaches for diabetes management during fasting have been used. Initially, prior to the era of glucometers and CGM, people with diabetes were exempt from fasting. In the last two decades, several studies showed that insulin dose adjustments and close monitoring may enable safe fasting for individuals with T1D.18-21 Jewish law indicates that specific medical counseling and liaison with Jewish legal scholars should facilitate and help to ensure safer fasting for the individual.19-21 Fasting is also common in other religions in the world. It is well known that followers of Hinduism, Buddhism and Jainism believe that the act of fasting would result in the spiritual transformation of the individual or community. In Hinduism, different forms of fasting are frequently practised throughout the year. Fasting is not considered an obligation, but a spiritual and moral act, the aim being to purify the body and mind to acquire self-restraint and divine grace. There are different forms of fasting which vary according to personal, family and community beliefs, which may be strict and difficult to follow, or relatively easy and readily amenable to modifications. The fasting period can be for a single day, weekly (on specific day/s throughout the year), bi-monthly (Pradosha—13th day of every fortnight of the Hindu calendar), monthly (Ekadashi—11th day of the Hindu lunar month, and Purnima—the full moon day). Longer fasting periods may last 9 days and are followed once or twice a year (Navratras), or of 1-month duration (Kartik month). Variability exists according to timing, duration and type of food intake, including no food and water intake, only water allowed; fruit and milk allowed, and broken rice or millets allowed.22 In Buddhism, while fasting is generally practiced by monks, lay people may fast voluntarily as part of a personal spiritual observance. Buddhist Lent is the fast and feast observed for three lunar months every year during the rainy season, when Buddhists fast for a 12-h period, from noon to midnight, followed by feasting for 12 h from midnight to noon.23 Some devout lay Buddhists also follow the rule during special days of religious observance when one must not eat after the noon meal. The duration of fasting can vary from three (sanzhai) to 6 days (liuzhai).24 In the first half of the first, fifth, and ninth months, a continuous long fast (changzhai) is also observed. Fasting is similarly prevalent in Jainism, observed during festivals, holy days, birthdays and anniversaries. There are several types of fasts, varying from 24–36 h to several days and months. Paryushan is the main festival during the monsoons, which usually lasts eight or 10 days, respectively, in the Swetambara and Digambara Jain tradition (the two main sects of Jainism).25 Digambar Jains usually will not consume food and/or water (boiled) more than once in a day; while Shwetambar Jains drink only boiled water during their fast days. Many Jains observe a type of fasting by abstaining from food and water after sunset. Varshitap (year-long fast) is a type of fasting in Jainism where devotees fast for 13 months and 13 days, in which they fast completely on alternate days and eat a limited diet between sunrise and sunset on the other days. The Bahais fast for 19 days in the month of Ala (March), when no food or water is consumed from sunrise to sunset by persons 15–70 years old. In Taoism, fasting is observed in the form of “Bigu,” where grains are avoided. Many reviews, consensus statements, and expert opinions detailing the principles of diabetes care during fasting (especially during Ramadan) have been published.5-7, 26-28 A comprehensive guide has been developed by the International Islamic Fiqh Academy, along with the Islamic organization of health sciences, after a thorough literature review of possible risks to people with diabetes associated with Ramadan fasting. Among defined risk stratification groups, T1D is considered to be a very high-risk group.29, 30 However, this document is not specific to young people with diabetes, and overall studies on religious fasting in this population are limited.31 A survey by Elbarbary et al. highlighted variations among physicians, from 16 predominantly Muslim countries, in the management of children and adolescents with T1D. There are substantial variations in the perceptions, beliefs, general management, and the practice of insulin therapy in this age group during fasting.32 The survey also highlighted limitations related to relying on data on the safety and metabolic impact of fasting based on studies conducted in adults with T2D.32 Furthermore, there is minimal literature on fasting-related issues in religions other than Islam. In many diabetes centers managing Muslim populations, healthcare professionals agree that adolescents can fast if they have reasonable glycemic control, good hypoglycemia awareness, and the willingness to frequently monitor their BGLs during fasting.33 A recent survey indicated that almost 80% of physicians looking after children and adolescents with diabetes would allow them to fast if they wished.32 Pre-fasting assessment and education are vital to ensure the suitability and safety of fasting in young people with diabetes. Many diabetes units run special education sessions prior to the month of Ramadan to ensure safe fasting. The lack of pre-fasting assessment and proper diabetes education are major obstacles for safe fasting in people with T1D.32, 34 Eid et al. showed that an educational program consisting of weekly sessions before and during Ramadan, enabled people with diabetes to fast safely, with a reduced number of hypoglycemic events per month.35 A systematic review showed that Ramadan-focused diabetes education in T2D resulted in a substantial reduction of hypoglycemia and improvement in HbA1c.36 Structured education has also been associated with a 61% decrease in DKA risk in adults with T1D.37 The dose adjustment for normal eating (DAFNE) education program highlights the importance of flexible dosing, carbohydrate counting and matching insulin to carbohydrate intake.38 This, together with rtCGM or isCGM, can help people with uncomplicated T1D to safely fast during Ramadan.39, 40 In a study from Kuwait, people with T1D using CGM and provided with DAFNE training had a reduced incidence of hypoglycemia during Ramadan compared with the pre-Ramadan period. No episodes of severe hypoglycemia, DKA, acute kidney injury, or hospitalization occurred during Ramadan, including no evidence of increased glucose variability.39, 40 Other studies demonstrated that individuals with T1D who received Ramadan-focused education showed more willingness to fast, since they were more capable of managing their diabetes, and they had better glycemic outcomes and fewer complications.41, 42 Qualitative studies suggest that structured Ramadan-focused education needs to be developed and implemented in clinic practice.38, 41, 43 The DAR practical guidelines 2021 also suggested that individuals with diabetes wishing to fast and receiving pre-Ramadan assessment and education, should fast for a few days during the 2 months preceding Ramadan.9 In summary, wider implementation of fasting-focused education for both individuals with T1D and T2D, especially those on insulin therapy, is of paramount importance. Based on the growing number of technologies that support diabetes care, telemedicine has been proposed as an important solution to meet the need of expanding care for the benefit of people with diabetes, while improving efficiency and containing costs.44 During the COVID-19 pandemic, telemedicine and telemonitoring have shifted from an aspirational goal to a de facto standard of care for diabetes management.45 Limited studies have investigated the role of telemedicine in the management of diabetes during Ramadan or other religious fasting, especially in adolescents with T1D. In 2020 and 2021, the Holy Month of Ramadan coincided with the COVID-19 pandemic and lockdown. Limited access to healthcare and the continuous need for diabetes assessment and consultation before and during Ramadan highlighted the urgent need for digital health solutions in diabetes care. The DAR Global Survey on 1483 Muslim participants with T1D showed that 26.8% of those aged <18 years and 73.2% of those aged ≥18 years fasted during Ramadan during the 2020 COVID pandemic.46 When comparing the short-term benefits of a telemonitoring-supplemented focused diabetes education with education alone in individuals with T2D who fasted during Ramadan, frequency of hypoglycemia was lower in the telemonitored group.47 Similarly, the “Making Ramadan Fasting A Safer Experience (MRFAST)” study showed reduced episodes of hypoglycemia and greater reduction in HbA1c in participants with T2D assigned to the telemonitoring group compared to the control group.48 Participants viewed telemedicine as a more convenient alternative, although technological barriers remain a concern. A prospective study assessed the role of a 24-h Helpline Service for people with diabetes during Ramadan and supported its key role in promoting safe fasting and reducing unnecessary hospital visits and admissions.49 More than half of the 927 calls were queries related to glucose monitoring data and insulin dose adjustment in T1D. Overall, telemonitoring offers an attractive option for managing diabetes during Ramadan and other religious fasting, but further data in adolescents with diabetes are needed.50 In healthy individuals, during fasting circulating BGLs tend to fall leading to decreased insulin secretion. In addition, levels of glucagon and catecholamines rise, stimulating glycogenolysis and gluconeogenesis.51 In the early hours of fasting, glycogenolysis meets the glucose requirements of the body. This is followed by gluconeogenesis, and later ketogenesis, if the duration of fasting is prolonged. Similar responses, albeit to a lesser extent, occur during the intermittent fasting that occurs during Ramadan. In people with T1D, hypoglycemia that occurs during fasting may not elicit an adequate glucagon response.52, 53 In addition, individuals with autonomic neuropathy can have defective epinephrine secretion to counteract hypoglycemia.54 In individuals with T1D fasting during Ramadan or other religious observances, abnormalities in the counter-regulatory hormones (glucagon, cortisol and catecholamines) may also be present due to disruption of the normal circadian rhythms and the sleep-wake cycle. In addition, there is risk of hypoglycemia associated with exogenous insulin treatment during fasting with changes in meal timing.53 Several studies have focused on the changes in glucose homeostasis during Ramadan fasting. In a study in young adults without diabetes55 using CGM 1- to 2 weeks before, in the middle and 4 to 6 weeks after Ramadan, an increase in the hyperglycemic area above 140 mg/dl was noted after Ramadan, compared with both before and during Ramadan, along with increased glucose variability.55 However, limited data are available on the safety and metabolic effects of fasting in children and adolescents with T1D.3 In a study assessing the impact of Ramadan fasting on resting metabolic rate (RMR), activity, and total energy expenditure (TEE), fasting was associated with reduced physical activity and reduced RMR, without an overall reduction in TEE. Ramadan differs from both prolonged and short-term starvation, as the former decreases RMR, whereas short-term starvation may increase RMR, and this has been attributed to a rise in norepinephrine concentrations.56 Many adolescents with T1D prefer to fast to feel equal to their peers without diabetes.57 Fasting may boost their self-esteem and make them happier as they feel “mature and capable” in fulfilling their religious obligations. However, considering the risk of acute metabolic complications in individuals with T1D, they are often advised not to fast.5-7, 26, 28, 58 Despite the fact that having diabetes grants an exemption from fasting, a large number of youth with diabetes are passionate about Ramadan, and undergo fasting based on social and cultural reasons and a religious sense of fulfillment.3, 57 Young people with diabetes may often fast without the knowledge or approval of their physicians.59 Predictably, there is a general fear among persons with T1D and their health-care providers about the use of insulin therapy during the fast, due to the increased risk of hypoglycemia.60 Hypoglycemia during the daytime is the most disliked complication as its treatment entails the intake of carbohydrate and therefore leads to breaking the fast prematurely. The interruption of fasting may induce a sense of guilt and failure.61 Data indicate that the majority of Muslim adolescents and older children with T1D are able to fast during Ramadan, with a high proportion of them encouraged by their parents to do so.61 Their expectations of developing complications are realistic, but they underestimate the deterioration in glycemic control during the month. It is reassuring that the majority agree to break their fast should complications arise, which makes fasting safer for them. The DEAR program (Diabetes Education and medication Adjustment in Ramadan) aimed to optimize glycemic control prior to Ramadan, and provide risk assessment, preparation, monitoring and intervention pre-, during and post-Ramadan.62 The program was also initiated to focus on covering the relevant religious and medical aspects through engaging a religious leader and Muslim healthcare professional team. The study highlighted that deficiencies in knowledge among healthcare professionals regarding Ramadan fasting can lead to people with diabetes choosing not to inform their healthcare team that they will fast, particularly in Muslim minority countries.62 Depending on where the adolescents live, they often attend school for the whole day, and partake in after-school activities, including sports, during Ramadan, even though they experience sleep disturbances and changes to routines, with late-breaking of the fast and waking early to have the pre-dawn Suhoor. For adolescents with T1D, fasting adds more challenges, especially for those living in Muslim minority societies, where there may not be adjustments made to school and sports schedules, particularly when the hours of fasting are longer (summers). The psychological effects of fasting during Ramadan can vary. Both healthy individuals and people with diabetes can experience opposing psychological outcomes for different reasons, including the changes that accompany the practice of fasting.63 Further research is needed to assess the psychological effects of fasting during Ramadan in adults as well as adolescents with T1D or T2D. Potential risks associated with fasting are hyperglycemia, hypoglycemia, DKA, thrombotic episodes, and dehydration.5-7 Although most of the available data are based on adult studies, an individualized approach, close monitoring of BGLs and weekly follow-up with the medical team is the best approach to prevent acute complications in both adults and young people with diabetes.64 Data on the impact of Ramadan fasting on glycemic outcomes are based on few small studies with inconsistent results. Some studies in children with diabetes demonstrated a significant improvement in fructosamine levels, whereas others showed no changes, or even an increase in HbA1c levels.57, 61, 65-68 Some studies3, 68 have shown that Ramadan fasting in individuals with T1D might predispose to acute complications, although this has not been confirmed by others. Overall, fasting can be considered a safe practice if people with diabetes monitor BGLs frequently and break the fast when hypoglycemia or marked hyperglycemia occur18, 58, 64, 69, 70 Besides, Ramadan fasting has been found safe when pre-fasting medical assessment, focused education, appropriately adjusted insulin regimens, diet control, and management of daily activities have been implemented in individuals with stable diabetes control and no comorbidities57, 68, 70 Studies have shown that adolescents are able to fast for several days during the Ramadan month,71, 72 but unplanned fasting may predispose to hypoglycemia and hyperglycemia with or without ketosis.28, 59 Hypoglycemia is a major complication of fasting. The EPIDIAR study of 1070 adults with T1D reported that fasting during Ramadan increased the risk of severe hypoglycemia by 7.5-fold. During Ramadan, 2% of people with diabetes experienced at least one episode of severe hypoglycemia requiring hospitalization.3 In a pediatric study symptomatic hypoglycemia resulted in breaking the fast on 15% of the days.72 In addition, CGM data have shown wide BGL fluctuations during fasting and eating hours and episodes of unreported hypoglycemia.72 The frequency and duration of hypoglycemia, hyperglycemia, and severe hyperglycemia were significantly higher in adolescents with T1D who had pre-Ramadan suboptimal than those with good glycemic control.73 In a retrospective study of 50 children and adolescents with T1D (age 12.7 ± 2.1 years), those with HbA1c >8.5% had more frequent episodes of hypoglycemia than those with HbA1c ≤8.5%.74 Hypoglycemia has been typically encountered during the hours preceding Iftar.75 Young adults with suboptimal management of T1D experienced wide fluctuations in glucose levels between the fasting and eating hours, with a greater tendency toward hyperglycemia.76 Monitoring BGLs during fasting is essential to predict, prevent, and treat hypoglycemia. It is of paramount importance that BGL is checked if any symptoms suggestive of hypoglycemia are experienced, so that the fast is interrupted promptly. However, some young people may not be willing to break their fast, particularly if hypoglycemia occurs close to sunset (time to end the fast for the day), and this may predispose them to a severe hypoglycemia. A study of 33 children with T1D in Bangladesh showed that only 3 out of 13 children broke their fasting following onset of symptoms of hypoglycemia.77 However, in another study61 most children and adolescents were willing to terminate their fasting when hypoglycemia occurred, regardless of the time of the day. Education might persuade young people with diabetes to break the fast when hypoglycemia occurs. Fasting increases glucagon levels and accelerates lipolysis and ketosis. These pathophysiological changes, in conjunction with fasting itself, may lead to metabolic decompensation in people with diabetes. Episodes of DKA have been reported during Ramadan fasting.78, 79 Detection of euglycemic ketosis during fasting requires evaluation of acid–base state, blood glucose and ketone values (ideally blood ketone measurements, if available) to differentiate DKA from ketosis due to prolonged fasting.80 See ISPAD 2022 Consensus Guidelines Chapter 12 on Sick Day Management in Diabetes for further details on ketosis monitoring. Knowledge of insulin action, interpreting glucose values and adjusting insulin doses for Iftar and Suhoor meals, is a prerequisite for safe Ramadan fasting. Based on clinical experience, different recommendations on how to adjust the type, dose, and timing of insulin in adults have been suggested.69, 81, 82 However, clear evidence-based guidelines on insulin adjustment for adolescents with T1D are lacking. Current recommendations for people on multiple daily injections (MDI) include a reduction of the total daily dose (TDD) of insulin to 70%–85% of the pre-fasting TDD27, 82 or 60%–70% of the pre-fasting dose of basal insulin.7 For people on continuous subcutaneous insulin (CSII), a reduction of the basal rate of insulin infusion by 20%–40% in the last 3–4 h of fasting is recommended.7 The South Asian Guidelines for Management of Endocrine Disorders in Ramadan recommend reducing basal insulin by 10%–20% during the fast days.79, 80 However, these recommendations are not based on data from large cohort studies or randomized controlled studies. Some studies have not shown a reduction in frequency of hypoglycemia with reduction of basal insulin in MDI and CSII regimens, although this has not been confirmed by all studies.83, 84 A suggested guide for adjustment of insulin dosages is given in Figure 1. Management of diabetes during fasting should be discussed on an individual basis, depending on access to different insulins and technology. Once fasting has started, insulin dosing should be regularly adjusted based on the results of glucose monitoring. Frequent BGL measurement is essential. MDI and CSII are the preferred regimens in young people with T1D during Ramadan.85 In some regions, treatment with two or three daily injections with NPH and short-acting insulin may be used. Use of premixed insulin regimens require fixed intake of carbohydrates at set times and is not advised. Insulin analogs have been safe for the management of well-controlled young people with diabetes during a fasting period of 17–19 h. A significant decline in glucose levels, with periods of hypoglycemia, is seen mostly near the end of the fasting period, although no episodes of severe hypoglycemia have been reported.7, 57, 65, 69, 72, 86, 87 It is recommended that during Ramadan, the pre-Ramadan basal insulin dose should be reduced by 20%, when given in the evening.5, 27, 57, 68-71, 87 When taken at Iftar, a further reduction may be needed—up to 40% of the pre-Ramadan basal dose.7, 88 Further individualized adjustment of the dose needs to be considered. Based on the pharmacodynamic profile of NPH, there is a considerable risk of mid-day hypoglycemia and end-of-the-day hyperglycemia. Reduction of the dose is needed to prevent hypoglycemia, at the possible expense of higher BGLs at the end of the day. In most studies, the pre-Iftar and pre-Suhoor rapid-acting insulin doses are equal to the pre-Ramadan lunch and dinner doses, respectively. In some reports, the pre-dawn dose is reduced by 25%–50%,7 depending on the carbohydrate content of the meal and the pre-meal BGL. In an adult study, the use of rapid-acting insulin analogs was associated with fewer hypoglycemic events and an improvement in postprandial glycemia compared with regular insulin.89 Higher BGLs may require an additional dose of insulin administered as a correction dose, which is usually based on the pre-Ramadan correction factor. Two daily injections of NPH and regular insulin allow less flexibility in lifestyle and nutrition with more risk of hyperglycemia and hypoglycemia; therefore, their use is strongly discouraged. Owing to the NPH peak effect, dose adjustment for a 12–16 h period of fasting is more challenging.84 Children on a twice-daily insulin regimen are much more prone to experience hyperglycemia with/without ketones than those on a basal-bolus regimen.84 Using twice-daily insulin regimens during Ramadan requires more dose adjustments, taking the usual morning dose before the sunset meal and only sho