Section 1

Aabid is a 47-year-old with type 2 diabetes for 5 years. During his diabetes review at the GP surgery, he mentions that Ramadan is approaching during which he plans to observe daytime fasting. He asks for advice in managing his diabetes around the month of Ramadan.

Aabid’s current treatment consists of metformin 1 g twice daily, gliclazide 160 mg twice daily and atorvastatin 20 mg once daily. His HbA_1c has been measured at 65 mmol/mol, eGFR >90 mL/min, cholesterol 4.2 mmol/L, non-HDL 2.2 mmol/L, BP 136/86 mmHg and BMI 29.4 kg/m². He has no complications of diabetes.

What medical concerns might you have regarding Aabid observing Ramadan?

Section 2

Fasting during Ramadan takes place between sunrise (suhoor) and sunset (iftar), although the hours of fasting will vary considerably according to the time of year when Ramadan falls. The lunar-based Islamic calendar has 354 days, so Ramadan occurs 11 days earlier each year. Ramadan has a duration of 29 to 30 days (1).

The greatest concern for Aabid would be that of daytime hypoglycaemia associated with his use of gliclazide whilst he is fasting. Abstinence from drink as well as food during daylight hours is a requirement of Ramadan, so the risk of dehydration is also an issue. This may lead to postural hypotension and an accompanying risk of falls, notably in the elderly and those with a pre-existing autonomic neuropathy. Increased blood viscosity can predispose to thrombosis. Hot climates and heavy physical work or exercise may aggravate the problem (2).

Paradoxically, hyperglycaemia is also a potential problem during Ramadan. This may be explained by the propensity to eat unusually large quantities of food between sunset and sunrise. Additionally, there may be discontinuation of diabetes medications because of concerns over hypoglycaemia.

The EPIDIAR study of 12,000 patients with diabetes in 13 countries found that the risk of severe hypoglycaemia increased during Ramadan, compared with other months (nearly 8 times higher in type 2 diabetes) (3). For subjects with type 2 diabetes, this risk was highest in those using insulin, ahead of those using oral agents alone. The CREED study also reported a (less pronounced) increase in hypoglycaemia in subjects with type 2 diabetes who fasted during Ramadan (4).

The risk of severe hyperglycaemia during Ramadan predisposing to hyperosmolar hyperglycaemic state (HHS) in type 2 diabetes was also found to be increased in the EPIDIAR study (3).

As a Muslim with type 2 diabetes, is Aabid obliged to observe Ramadan fasting?

Section 3

Vulnerable people with diabetes are one group that can be exempted from fasting during Ramadan.

Risk stratification has for some time been seen as crucial to the management of diabetes during Ramadan. The aim here is to assess the risk of complications to an individual of fasting, taking into account the type of diabetes, medication, risk of hypoglycaemia, comorbidities and personal circumstances (5). The recent IDF–DAR guidelines (2) advise that individuals with diabetes in the very-high-risk and high-risk categories should not fast during Ramadan (the advice being very stringent in the case of very-high-risk individuals). Those in the moderate/low-risk category may be suitable for fasting after discussion with their doctor (see below).

Category 1. Very high risk; one or more of:

• Severe hypoglycaemia within 3 months prior to Ramadan.
• DKA or HHS within 3 months prior to Ramadan.
• Recurrent hypoglycaemia or hypoglycaemic unawareness.
• Poorly controlled type 1 diabetes.
• Acute illness.
• Pregnancy in pre-existing diabetes or gestational diabetes with use of insulin or sulfonylureas (SUs).
• CKD stage 4 or 5, chronic dialysis.
• Advanced macrovascular complications.
• Old age with ill health.

Category 2. High risk; one or more of:

• Type 2 diabetes with sustained poor glycaemic control.
• Well-controlled type 1 or type 2 diabetes on insulin regimen more complex than basal insulin.
• Pregnant type 2 diabetes or gestational diabetes controlled with diet only or metformin.
• CKD stage 3.
• Stable macrovascular complications.
• Intense physical labour.
• Treatment that may affect cognitive function.
• Significant comorbidities.

Category 3. Moderate/low risk:

• Well-controlled type 2 diabetes not using insulin.

Is Aabid at high risk of complications from fasting?

Section 4

In fact, as an individual with type 2 diabetes with reasonable glycaemic control, not using insulin – and in the absence of diabetes comorbidities – Aabid would be classed as being at low to moderate risk of having complications arise during fasting.

Many Muslims with diabetes feel strongly committed to observing Ramadan, and the EPIDIAR study estimated up to 79% of those with type 2 diabetes fasted during Ramadan (3). The later CREED study found that an even higher proportion of individuals with type 2 diabetes fasted during Ramadan (4).

Aabid is keen to go ahead with fasting during Ramadan. What could you usefully discuss with him?

Section 5

A good starting point would be to ask about Aabid’s previous fasting experience during Ramadan and, specifically, if he encountered any problems. Check his current medication and recent glycaemic control, as evidenced by HbA_1c, and, where appropriate, blood glucose profiles. Does Aabid experience any hypoglycaemia and what is his level of hypoglycaemic awareness? Review Aabid’s comorbidities and medical history, and take into consideration personal circumstances such as occupation and exercise.

Armed with this information you can then provide advice on diet and fluids, and the need for medication adjustment (see below). Capillary blood glucose monitoring, setting of blood glucose targets, and how to manage hypoglycaemia (including when it is necessary to break fast) and hyperglycaemia can be discussed.

Aabid should have a point of contact, should problems arise.

Diabetes education ahead of Ramadan is associated with reduced episodes of hypoglycaemia and improved glycaemic control (2).

What general advice on fluids and diet might you advise during Ramadan?

Section 6

Offering specific dietary advice during Ramadan can be difficult for non-Muslim healthcare professionals, as this requires knowledge of the dietary habits of the local Muslim population. It is likely that Aabid has a well-established routine for eating during Ramadan.

For individuals with diabetes observing Ramadan, however, it is advisable to eat starchy carbohydrates that release energy over a long period of time (i.e. low glycaemic index). This is of particular importance at the pre-dawn meal (suhoor), which has to provide energy during the fasting period. Suitable foods might include oat-based cereals, wholegrain bread, basmati rice, chapatis and pitta bread, along with beans, pulses, lentils, and fruit and vegetables (6,7). It is advisable to take suhoor as late as possible.

There is a danger of overeating in the non-fasting period, leading to hyperglycaemia. Dietary moderation, most notably at the post-sunset meal (iftar) should be encouraged.

A good fluid intake in the non-fasting period is of great importance to counter dehydration.

Exercise should be undertaken with caution during fasting to reduce the risk of hypoglycaemia and dehydration.

Section 7

Aabid does experience occasional mild hypoglycaemia during the day. This has been problematic during previous periods of Ramadan, although he retains good awareness of symptoms of hypoglycaemia. Aabid does not routinely monitor capillary glucose levels, but does have a monitor and test strips.

How might you consider altering Aabid’s gliclazide dose for the upcoming Ramadan in view of his hypoglycaemia?

Section 8

The priority for Aabid is to avoid hypoglycaemia during the fasting period.

Gliclazide predisposes to hypoglycaemia and this risk will be greatest following the morning dose at suhoor ahead of the fasting period. Thus, you could consider reducing the morning dose of gliclazide to 80 mg. Advise Aabid to keep a close eye on glucose levels with regular monitoring. Reassure him that glucose testing does not break the fast (agreed by religious leaders). Advise Aabid to check glucose readings before suhoor and iftar as a minimum, and also at any time where he may experience symptoms of hypo- or hyperglycaemia. Hypoglycaemia should be dealt with as a matter of urgency (as agreed by religious leaders).

It is considered safer to use shorter-acting, second-generation SUs (such as gliclazide and glipizide), rather than the longer-acting glibenclamide (8,9). A sensible precaution is to weight the dose of SU towards the evening meal or, in the case of once-daily SU, to take this at iftar. As a general rule, the largest dose of an oral hypoglycaemic agent should be given in the evening (i.e. at iftar).

Can you think of other options, instead of gliclazide, to reduce Aabid’s risk of hypoglycaemia during Ramadan?

Section 9

You might consider switching Aabid from gliclazide to a DPP-4 inhibitor (gliptin), as this class of medication confers a low risk of hypoglycaemia. There is evidence that the incidence of hypoglycaemia during Ramadan is significantly lower in those taking a gliptin compared to an SU, with at least as good glycaemic control (9–11). Probably the optimal time to take a gliptin is with the post-sunset meal, which synchronises peak activity of the drug with the heaviest carbohydrate load.

The meglitinides (repaglinide and nateglinide) act as insulin secretagogues and, in common with SUs, can induce hypoglycaemia. However, their faster onset and shorter duration of action potentially offers less risk of hypoglycaemia (than SUs) during the fasting period following the morning dose, making them a more attractive option to be taken with suhoor and iftar (12).

How suitable for use in Ramadan are other classes of medication for type 2 diabetes?

Section 10

Metformin carries a low risk of hypoglycaemia and remains a first-choice treatment for type 2 diabetes during Ramadan. If dosing is asymmetrical, then the higher dose should be taken at iftar (post-sunset meal). Similarly, modified-release metformin is best taken at iftar to deal with the overnight carbohydrate load.

The thiazolidinedione pioglitazone is effective in improving glycaemic control during Ramadan and can be continued without dose change, as it does not have a propensity to induce hypoglycaemia.

The SGLT2 inhibitors carry a low risk of hypoglycaemia. However, the glycosuria they induce is associated with fluid loss. This raises the concern that they could aggravate dehydration and postural hypotension (notably in the elderly in hot weather), as well as predisposing to DKA in the starved state (13,14). A study comparing dapagliflozin with SU therapy in subjects with type 2 diabetes during Ramadan confirmed a reduction in hypoglycaemia and, reassuringly, did not find an increased risk of dehydration and postural hypotension (14). Sensible precautions when using SGLT2 inhibitors during Ramadan would be to take them with the post-sunset meal and ensure good fluid intake during the non-fasting period.

The GLP-1 receptor agonists are considered safe to use during the Ramadan fast without dose modification. Their propensity to cause hypoglycaemia is low. The safety and efficacy of liraglutide compared to SU therapy was demonstrated in the Treat 4 (15) and LIRA-Ramadan (16) trials, in which the liraglutide groups achieved superior glycaemic control and weight control together with a reduced incidence of hypoglycaemia.

Section 11

Aabid has been doubly vaccinated against COVID-19 infection, with his booster dose due during the period of Ramadan. He asks your advice on whether he should proceed with his booster vaccination and what he should do if he were to contract COVID-19 infection during Ramadan.

How should you advise Aabid?

Section 12

As an Asian person with diabetes, Aabid is at increased risk of severe complications from COVID-19 infection. Full vaccination is, therefore, crucial in protecting his health. The British Islamic Medical Association has made clear that vaccination does not invalidate the Ramadan fast, so encourage Aabid to attend for his booster vaccination (17). He should follow the current recommendations for social distancing and mask wearing, and the advice in regard of religious gatherings provided by the Muslim Council of Britain (18).

If Aabid does contract COVID-19 infection, he should follow the recommendations regarding testing and isolation. As with other significant illnesses, Aabid is allowed to break fast and, importantly, maintain adequate hydration. He should seek medical advice if necessary. Fasting may be resumed when health has returned to normal (1).

Section 13

Jameela is a 56-year-old woman of Muslim faith, with type 2 diabetes for 11 years. She is maintained on metformin 1 g twice daily and NovoMix 30 insulin (34 units with breakfast and 28 units with evening meal). Capillary blood glucose readings are in the range 5–11 mmol/L both pre-breakfast and pre-evening meal, and this translates to an HbA_1c of 57 mmol/mol.

What advice would you give to Jameela over the advisability of fasting during Ramadan?

Section 14

Although Jameela’s hyperglycaemia is well-controlled, she falls into the high-risk category for complications (see above) – a person with type 2 diabetes using a biphasic insulin. Thus, following guidelines, you could explain to Jameela that, because of the risks involved, fasting is not recommended (by religious leaders in conjunction with diabetes experts) and that she can be exempted from fasting.

After discussion, Jameela indicates that she is determined to fast as she has done in the past during Ramadan.

There may be convincing medical reasons why fasting during Ramadan would be inadvisable for a person with diabetes, but the decision to fast or not lies with the individual. Healthcare professionals involved in their care need to support these individuals.

Jameela should receive structured education by the diabetes team responsible for managing her diabetes.

What is the greatest risk to Jameela from fasting during Ramadan?

Section 15

Hypoglycaemia during the daytime fast is probably the biggest risk for Jameela, especially as she is using insulin that includes a fast-acting component.

Jameela retains good awareness of hypoglycaemia.

How could you reduce the risk of hypoglycaemia for Jameela?

Section 16

A reduction in Jameela’s breakfast dose of NovoMix 30 insulin (of around 25%) would help to protect against daytime hypoglycaemia (similarly for other twice-daily, premixed biphasic insulins (e.g. Humulin M3; Humalog Mix25 and 50; Insuman Comb 15, 25 and 50).

Jameela should be instructed that close monitoring of fingerprick blood glucose levels should be practised. This should include readings before suhoor and iftar, and during the daytime fast, with additional measurements if there are symptoms of hypo- or hyperglycaemia or if feeling unwell (5). Ideal target glucose levels would be 5–9 mmol/L, but these should be individualised. A fast-acting supply of carbohydrate should always be carried, with instructions to break the fast should hypoglycaemia occur. Jameela should be reassured that these actions are not contrary to observing Ramadan.

What about other insulin regimens?

Section 17

Commonly in type 2 diabetes, the insulin regimen will consist of a basal insulin alone. If the individual is taking human isophane (NPH) insulin (Insulatard, Humulin I, Insuman Basal), the time–action profile of this insulin dictates that it should be administered with the evening meal (iftar) to deal with the overnight glucose load, but with reduced effects during the subsequent daytime fast. If a longer-acting basal insulin analogue (Levemir, Lantus, Toujeo, Tresiba, Abasaglar, Semglee) is being used, this is again best taken at iftar, but may require a reduction in dose of around 20% to avoid subsequent daytime hypoglycaemia (5). If the basal insulin is taken twice daily, then the dose at suhoor (pre-dawn meal) should be reduced (by up to 50%).

If fast-acting (prandial) insulins are being used, the suhoor dose of prandial insulin should be reduced by 25–50% to avoid daytime hypoglycaemia, and any midday dose omitted during the period of fast (5).

Advice will need to be individualised, responding to blood glucose profile. Community Diabetes Nurses and DSNs are important sources of information and advice.