Review of diabetes management and guidelines during Ramadan

Introduction

Demographics of the Muslim population

Islam is the second largest religion in the world and Muslims constitute approximately 22% of the world's population. According to latest data, the total number of Muslims in the world is over 1.5 billion. In Europe Muslims constitute approximately 7% of the overall population. In the UK the size of the Muslim population is estimated to be close to 1.6 million, constituting 2.7% of the overall population.¹ While diabetes affects 4% of the white Caucasian population, it affects 22% of Pakistani and 27% of the Bangladeshi Muslim population (aged 25–74 years).² The approximate number of Muslims in the UK with diabetes is estimated at 325,000.³

Most patients with diabetes are asymptomatic; they do not consider themselves as having an illness and fast during Ramadan. The concerns are fasting may lead to hypoglycaemia, hyperglycaemia with or without ketoacidosis, and dehydration. Another problem is the reluctance of patients in taking their medications during the fast, therefore timing and dosage of anti-diabetic agents has to be adjusted for individual patients. Despite all this, it must be pointed out that very few complications are actually seen in clinical practice.⁴ Managing Muslim patients with diabetes during Ramadan continues to be a challenge for healthcare professionals. This review is intended to offer a guide towards care of the Muslim patient with diabetes during Ramadan.

Why do Muslims fast?

The five pillars of Islam that form an integral part of faith are:

1. Shahadah – the declaration of faith;

2. Salah – five compulsory daily prayers;

3. Zakat – annual alms tax, to poor and needy;

4. Sawm – fasting during month of Ramadan;

5. Hajj – pilgrimage to Mecca.

The literal meaning of the word Sawm is ‘to refrain’ and here it means abstaining from food, drinks, smoking, intravenous fluids, intravenous and oral medications, and sexual activity from sunrise to sunset.⁵

What is Ramadan?

Ramadan is the ninth month in the Islamic calendar. It is based on a lunar calendar thus the duration of the daily fast and the overall length of the month of Ramadan vary according to geographical location and season; it precedes by 10–11 days every year.⁴ In Britain a fast can last for up to 19 hours during the summer months, and 10 hours during the winter months. The month of Ramadan generally lasts 28–30 days. Most Muslims eat two meals, before sunrise (known as Sehar) and after sunset (known as Iftar).⁵ Fasting is said to cultivate the spirit of sacrifice and teaches Muslims moral and self-discipline and sympathy for the poor.^5,6

Fasting is obligatory upon each sane, responsible and healthy Muslim. Certain individuals, however, are exempt from fasting:

• children under the age of puberty;

• those with learning difficulties (those unable to understand the nature and purpose of the fast);

• the old and frail;

• the acutely unwell;

• those with chronic illnesses in whom fasting may be detrimental to health;

• those travelling a distance greater than 50 miles in single journey.⁷

Methods

PubMed databases were searched using the key words ‘fasting’, ‘diabetes’ and ‘Ramadan’ between 1989 and 2009 for the purpose of this review. We identified 73 articles and classified them according to hierarchy of evidence:

• systematic reviews of randomized controlled trials;

• randomized controlled trials;

• controlled observational studies – cohort and case-control studies;

• uncontrolled observational studies.

There is a paucity of randomized controlled trials in this field, hence we had to rely on observational studies and international consensus guidelines and recommendations.

Physiology of fasting

Effects of fasting in normal people

Fasting has been advocated as a means for achieving spiritual purification from ancient times. Most research on the effects of fasting on metabolism has been conducted on the Muslim fast during the holy month of Ramadan.⁴

Effects on body weight

A study on the effects of fasting on body weight was conducted in 137 Jordanian adults. During this study the patients were divided into overweight, normal weight (controls) and underweight groups all of which showed significant weight reduction.⁸ A study of 81 healthy volunteer university students carried out at the Tehran University of Medical Sciences indicated that Ramadan fasting led to a decrease in glucose and weight. Weight, BMI, glucose and lipids were evaluated before and after Ramadan. Glucose levels reduced significantly during Ramadan and this effect was irrespective of gender; however, it had a significant correlation with weight. There were no changes in triglycerides and total cholesterol levels before and after Ramadan.⁹

Effects of fasting on glucose metabolism in normal healthy individuals

In normal healthy individuals eating stimulates the secretion of insulin from the islet cells of the pancreas. This in turn results in glycogenesis and storage of glucose as glycogen in liver and muscle. On the contrary, during fasting secretion of insulin is reduced while counter-regulatory hormones glucagon and catecholamines are increased. This leads to glycogenolysis and gluconeogenesis. The low levels of insulin in circulation also lead to increased fatty acid release and oxidation that generates ketones which are used for nutrition by the body (Figure 1).⁵

Figure 1.

Pathophysiology of fasting in normal individuals

Effects on lipid metabolism and other metabolic parameters during fasting

A recent study from Turkey suggested maternal serum cortisol level was elevated while the LDL/HDL ratio was reduced in healthy women with uncomplicated pregnancies of 20 weeks or more, who were fasting during Ramadan. No untoward effects of fasting were observed on intrauterine fetal development.¹⁰ A study of 30 healthy volunteers in Tunisia showed significant increase of plasma total and HDL-cholesterol. The most striking finding was a significant increase of 20% (p <0.02) in HDL-cholesterol during Ramadan. This increase was lost after Ramadan.¹¹ These findings have been confirmed in other studies.⁹

Pathophysiology of fasting in patients with diabetes

Effects of fasting on metabolism in patients with diabetes

Patients with type 1 diabetes and severe insulin deficiency may have excessive glycogenolysis, gluconeogenesis and ketogenesis. All of this may lead to hyperglycaemia and ketoacidosis that may be life-threatening. Some patients with diabetes have autonomic neuropathy leading to an inadequate response to hypoglycaemia ( Figure 2).⁵

Figure 2.

Pathophysiology of fasting in diabetes

Effects on body weight

The EPIDIAR study revealed weight was unchanged in the vast majority of patients with type 1 and type 2 diabetes.¹² Other studies also concluded either no change in weight or weight loss during Ramadan in patients with diabetes.^10,11

Effects on glycaemic control

Several studies have shown no significant change in glucose concentration in patients with diabetes.^10,11 However, there is an increased risk of severe hypoglycaemia, hyperglycaemia and ketoacidosis. The EPIDIAR study showed an increase in the risk of severe hypoglycaemia (defined as hypoglycaemia leading to hospitalization) of around 4.7-fold in patients with type 1 and 7.5-fold in patients with type 2 diabetes. On the other hand, the incidence of severe hyperglycaemia (requiring hospitalization) increased five-fold in patients with type 2 and three-fold in type 1 diabetes.¹²

Effects on lipid metabolism

Patients with diabetes show no change or a slight decrease in concentration of cholesterol and triglycerides. Several studies report an increase in HDL cholesterol therefore suggesting a theoretical decrease in cardiovascular risk.^13,14

Effects on other parameters

A survey from Saudi Arabia suggested an increase in the incidence of retinal vein occlusion during Ramadan: 29.5% of the attacks happened during Ramadan, which, when compared with other months of the Gregorian year, was statistically significant. The authors proposed dehydration might be responsible for this.¹⁵

Exemptions from fasting

An international consensus meeting of healthcare professionals and research scholars with interest in diabetes and Ramadan was held at Morocco in 1995. The aim of the meeting was to establish guidelines regarding patient groups who should be exempt from fasting. They concluded that the following groups should be exempt:

• type 1 diabetes;

• type 2 diabetes with unstable disease;

• diabetes with complications;

• pregnant women with diabetes;

• elderly patients with diabetes.

At the same time they also concluded that patients with diabetes who have stable disease should be allowed to fast even if they are on medications like biguanides or sulfonylurea.¹⁶

Current evidence of diabetes and fasting

A number of studies have looked at the management of diabetes during Ramadan. Most have targeted specific treatment modalities. However, the largest study looking at the management of diabetes during Ramadan is the EPIDIAR study, which had 12,243 participants.

The EPIDIAR study

This was a retrospective population-based study conducted in 13 countries including Algeria, Bangladesh, Egypt, India, Indonesia, Jordan, Lebanon, Malaysia, Morocco, Pakistan, Saudi Arabia, Tunisia and Turkey. Data were analysed from 12,243 participants: 8.7% had type 1 diabetes and the rest had type 2 diabetes. Nearly 43% of patients with type 1 diabetes and 79% of patients with type 2 diabetes reported fasting at least 15 days during Ramadan. Physical activity, sleep duration, food intake, fluid intake, and sugar intake were unchanged in half of the study population. Insulin dose was unchanged in 64% patients (type 1 and type 2 diabetes), and the doses of oral medications were unchanged in 75% of patients with type 2 diabetes. Severe hypoglycaemic episodes were significantly more frequent compared with other months (type 1 diabetes, 0.14 vs. 0.03 episode/month, P=0.0174; type 2 diabetes, 0.03 vs. 0.004 episode/month, P <0.0001). Similarly incidence of severe hyperglycaemia was higher during Ramadan (P=0.1635 and <0.001, respectively, for type 1 and 2 diabetes).¹²

Recommendations on management of diabetes during Ramadan

Pre-Ramadan medical assessment and counselling

All patients with diabetes wishing to fast during Ramadan should receive proper counselling 1–2 months before the onset of Ramadan. Assessment should include a full annual review, detection of complications along with measurements of HbA1c, blood pressure and lipids, as well as specific advice including potential risks of fasting. This is an ideal time to suggest any changes regarding diet as well as medications for treatment of diabetes. Educational counselling should focus not only on the patient but also his or her family about the awareness of symptoms of hypo- and hyperglycaemia, planning of meals, blood glucose monitoring, administration of medicines, physical activity as well as management of acute complications including when to break the fast ( Figure 3).⁵ This consultation also provides an opportunity to reinforce healthy living advice to the entire family and encourage patients to quit smoking. As patients are not allowed to smoke during fasting, this provides a unique opportunity to encourage patients to quit and offer help and advice as needed. A study looking at smoking cessation interventions among UK Bangladeshi and Pakistani adults noted how participants described a positive impact of fasting during Ramadan and pilgrimage to Mecca in helping them to quit smoking.¹⁷ Health promotional material is published regularly by the Department of Health and is available for use.¹⁸ In the EPIDIAR study, 68% of patients with type 1 diabetes and 61% of those with type 2 diabetes received pre-Ramadan diabetes advice.¹² Bain and colleagues from Birmingham showed only 40% of patients received any pre-Ramadan counselling.¹⁹

Figure 3.

Pre-Ramadan medical assessment and risk stratification

Nutrition

Patients should be advised to avoid food high in fat and sugar. It has been suggested that eating complex carbohydrate meals at dawn and simple carbohydrates at dusk may be more appropriate.⁵ Others suggest eating foods with long glycaemic indices when breaking the fast.⁷ Slow energy release foods like grains, wheat and rice are best before and after a period of fasting. The intake of ghee and fried snacks as well as high-fat and sugar-rich sweets should be minimized.²⁰

Physical activities

Taraweeh (Night prayer) is part of the customs of Ramadan and most men would normally walk to the local mosque; this should be considered a part of the daily exercise program.⁶ While normal levels of physical activity are encouraged, excessive exercise may lead to hypoglycaemia and should be avoided.⁵

Management of patients with type 1 diabetes

The general advice for patients with poorly-controlled type 1 diabetes is that they should not fast.⁵ However, data from the EPIDIAR study suggest approximately 43% of patients with type 1 diabetes fast during Ramadan.¹² If the patients decide to fast then they should be on a basal bolus regime, preferably on analogues and test sugars regularly. In two small studies, glargine has been shown to cause less hypoglycaemia.^21,22 In another study insulin lispro was given together with NPH insulin, twice daily before morning and evening meals, for two weeks each. Glycaemic control was improved and hypoglycaemia significantly reduced with insulin lispro compared to regular human insulin.²³

Management of patients with type 2 diabetes

Diet-controlled patients

This is a low-risk group that should be able to fast without problems. Caloric redistribution over smaller meals rather than eating one major meal may lead to less postprandial hyperglycaemia. Adequate fluid intake should be ensured in order to prevent the risk of thrombotic events.⁵

Patients treated with oral hypoglycaemic agents

Metformin

These patients should be able to fast safely as metformin is not associated with hypoglycaemia. However, it is advised that patients should change the timing of medications and take one-third at dawn and two-thirds at dusk.^5,7

Thiozolidinediones

Patients should be able to take their medications as usual with no adjustment in dosage required.^5,7 For those on combination treatments the dose should be adjusted to take half the tablet at dawn and 1.5 at dusk.⁷

Sulfonylurea and prandial regulators

These medications should be used with caution because of the risk of hypoglycaemia. A study from Turkey looked at the effects of diet, sulfonylurea and repaglinide therapy. Most parameters were not changed and only one hypoglycaemic event occurred in a patient taking glimepride.²⁴ A study by Belkhadir looked at the use of glibenclamide in 591 patients and concluded it was safe.²⁵ An open-labelled prospective observational study from six countries looked at the use of glimepiride in 332 patients with type 2 diabetes. The incidence of hypoglycaemic episodes was 3% in newly-diagnosed patients and 3.7% in already-treated patients. These figures were similar to the pre- and post-Ramadan periods.²⁶

Mafauzy carried out a study in which 235 patients, previously treated with a sulfonylurea, were randomized to receive either repaglinide or glibenclamide. A statistically significant reduction in serum fructosamine and no difference in HbA1C were identified. The number of hypoglycaemic events was significantly lower in the repaglinide group (2.8%) compared to glibenclamide group (7.9%).²⁷ A study from Turkey looked at comparing glycaemic effects of glimepiride, repaglinide and insulin glargine. No difference between the therapies was identified.²⁸ General advice is to use prandial regulators and short acting agents for the purpose of managing diabetes during Ramadan.

Incretin-based therapies (exenatide and gliptins)

Incretin-based therapies like DPP 4 inhibitors and GLP 1 analogues have shown to cause less hypoglycaemia when compared to conventional treatments and hence may be suitable for Ramadan. This is because GLP-1 acts in a glucose-dependent manner and, therefore, the risk of severe hypoglycaemia is less compared to other agents. When used alone they do not require any adjustments to their doses but the risk of hypoglycaemia in combination with sulfonylureas remain high. However, these are new agents and very few studies are currently available to draw firm conclusions. One of the concerns regarding injectable GLP-1 analogues is nausea and this could be a limiting factor during fasting.

The incidence of hypoglycaemia with Vildagliptin, an oral DPP 4 inhibitor, was less when compared to glimepride.²⁹ A meta-analysis on the randomized controlled trials with exenatide showed that severe hypoglycaemia was rare. Mild to moderate hypoglycaemia was 16% versus 7% (exenatide versus placebo) and more common with co-administration with sulfonylurea.³⁰

Similarly pooled analysis of 5141 patients in clinical trials for ≤2 years showed that sitagliptin monotherapy or combination therapy (metformin, pioglitazone, sulfonylurea, or sulfonylurea and metformin) was well-tolerated and hypoglycaemia occurred in the setting of combination therapy with sulfonylurea only.³⁰

Insulin

The general advice for long-acting insulin (glargine and detemir) is to reduce the dose by 20%. The rationale is to try and reduce the risk of hypoglycaemia. Long-acting insulin should be administered with the evening meal at dusk. Short-acting insulin analogues are also useful during fasting as they can work immediately following meals.²⁰ Bruttomesso et al. showed that positive metabolic effect of rapid-acting insulin analogues may last for up to 6 hours following ingestion of food.³¹ For premix insulins, the morning insulin dose should be taken at dusk and half of the evening dose should be taken at dawn.²⁰ During fasting human soluble insulins may remain in the system for 8–12 hours and, with their late long-lasting peak starting 2 hours after administration, can potentially lead to late postprandial hypoglycaemia. It is recommended that the newer insulin analogue preparations may be more useful in managing diabetes during Ramadan.³²

Table 1 illustrates general guidelines for the change in the diabetes regime before and during Ramadan. Although the insulin regimes are not extensive, they should be tailor-made to the individual patient depending on diet and lifestyle, close monitoring of blood sugars and baseline glycaemic control.

Table 1.

A rough guide of optimization of anti-diabetic medications during Ramadan

Before Ramadan	During Ramadan
Diet controlled	No change needed
Biguanides
Metformin 500 mg TDS	Metformin 1000 mg (sunset – Iftar), 500 mg (dawn – Sehr)
Metformin SR 1000 mg OD	Metformin 1000 mg (sunset – Iftar)
Thiazolidinediones	No change required
TZD+Biguanide combination
Avandamet BD	Avandamet –1 tablet (sunset – Iftar), Half tablet (dawn – Sehr)
Sulphonylureas
Gliclazide 80 mg BD	Gliclazide 80 mg (sunset – Iftar), 40 mg (dawn – Sehr)
Glimepiride 4 mg OD	Glimepiride 4 mg (sunset – Iftar)
Prandial regulators
Repaglinide 4 mg BD	No change(taken with Iftar and Sehr)
Incretin mimetics: DPP 4 inhibitors	No change; if taken with SU, will need dose reduction
Vildagliptin 50 mg BD
Sitagliptin 100 mg OD
Saxagliptin 5 mg OD
GLP 1 Analogues	No change (may need dose reduction if severe nausea, or if used in combination with SU)
Liraglutide 1.2 mg OD
Exenetide 10 mcg BD
Insulin
Once daily Glargine 20 units	Glargine 16 units (20% decrease in dose) with Iftar
Pre-mixed insulin – Novomix 30–30 and 20 units	10 units (dawn – Sehr) and 30 units (sunset – Iftar)
Novorapid/Humalog 10 units tds with each meal	Omit afternoon dose; twice daily with Iftar and Sehr meals

Advice on breaking the fast

Although fasting is one of the pillars of Islam, when fasting may affect health adversely Islam provides an exemption from fasting.

‘Fasting is for a fixed number of days, but if any of you is ill, or on a journey, the prescribed number (missed) should be made up …’ (Al-Qur'an, 2:184)

There is resistance among Muslims about breaking the fast even if there are serious health concerns. All patients should understand that they will need to break the fast if blood glucose is <3.3 mmol/L or exceeds 16.7 mmol/L.⁵ They should be advised to break the fast if blood glucose is <3.9mmol/L in the morning if the patient is taking sulfonylurea or insulin.⁵

Conclusion

Culture and religion have a great impact on the management of chronic disease like diabetes. For a growing Muslim population in the Western world, fasting during Ramadan is a central pillar of faith. We need to engage with reality that many patients will continue to fast during Ramadan despite medical advice. Indeed the EPIDIAR study showed 43% of patients with type 1 and 79% with type 2 diabetes fasted for at least for 15 days. Hence, it is important that healthcare professionals are well-informed regarding the effects of Ramadan on diabetes and are able to offer advice, guidance and change of medications as required during pre-Ramadan counselling to enable patients to fast safely should they wish to do so.

The aim of this review was to examine the current evidence and guidelines for fasting and management of diabetes during Ramadan. Although studies in literature have suggested safe management of patients with type 2 diabetes on a number of combination therapies, there have been no randomized controlled studies. Most of the previous studies have been carried out in the Middle East or South East Asia where time zone fluctuations between summer and winter are minimal. On the other hand, in European countries this is a major factor as fasting may last for up to 19 hours during summer months and can be as short as 10 hours during winter,

The general advice regarding type 1 diabetes is similar to other groups (Al-Arouj and others), i.e. patients with type 1 diabetes should be strongly advised to not fast. The EPIDIAR study suggested that despite this advice being available about half of patients with type 1 diabetes continued to fast. An important part of the management is to educate the patient, alter their therapy with clear guidance as when to break fast. This could be achieved by pre-Ramadan counselling that will give an opportunity to educate patients about fasting and diabetes, at the same time adjusting their medication as required, and also educate and encourage smoking cessation. This would be in keeping with the whole spirit of fasting and the patients who manage to abstain from smoking during the whole day could be motivated to give up smoking on a long-term basis. We know from previous studies that only half of the patients do get any kind of counselling or advice regarding fasting. One way of improving awareness and education regarding fasting would be to incorporate in diabetes education a programme like BME DESMOND, enabling patients to seek such advice before fasting. Second, this article aims to educate healthcare professionals in having a better understanding of Islam and attitudes of Muslims towards fasting and at the same time offering clear guidelines regarding management. One of the difficulties for a review like this is a paucity of good randomized trials as a whole and especially from Western countries as a long duration of fasting during summer months has an impact on diabetes. Studies are needed to examine the effect of education on patients, especially as a part of structured education programmes like DESMOND and Expert Patient. The incidence of diabetes complications like hypoglycaemia and diabetic ketoacidosis need to be studied in prospective trials. The use of guidance and dose adjustment through pre-Ramadan counselling also needs to be looked into through a multicentre trial. The newer agents for management of diabetes like incretin-based therapies may have a role, as they do not cause hypoglycaemia hence not requiring dose adjustments. However, these agents are new and have no published studies so far on their effect during Ramadan.

Recently Diabetes UK and South Asian Health Foundation published research priorities of diabetes in South Asians and Ramadan was identified as an important area for further research. This hopefully is a step in the right direction to address gaps in our knowledge in diabetes management during Ramadan.

Footnotes

DECLARATIONS —

Competing interests None declared

Funding None

Ethical approval Not applicable

Guarantor WH

Contributorship All authors contributed equally