key: cord-1010032-m0qqf4n7
authors: Hanif, S.; Ali, SN.; Hassanein, M.; Khunti, K.; Hanif, W.
title: Managing People with Diabetes Fasting for Ramadan During the COVID‐19 Pandemic: A South Asian Health Foundation Update
date: 2020-04-25
journal: Diabet Med
DOI: 10.1111/dme.14312
sha: e8fc1d547cb4f49326f6d1d2d8951190a23dc60a
doc_id: 1010032
cord_uid: m0qqf4n7

The month of Ramadan forms one of the five pillars of the Muslim faith. Adult Muslims are obligated to keep daily fasts from dawn to sunset, with exceptions. This year Ramadan is due to begin on 23 April 2020 and the longest fast in the UK will be approximately 18 hours in length. In addition, due to the often high‐calorie meals eaten to break the fast, Ramadan should be seen as a cycle of fasting and feasting. Ramadan fasting can impact those with diabetes, increasing the risk of hypoglycaemia, hyperglycaemia and dehydration. This year, Ramadan will occur during the global COVID‐19 pandemic. Reports show that diabetes appears to be a risk factor for more severe disease with COVID‐19. In addition, the UK experience has shown diabetes and COVID‐19 is associated with dehydration, starvation ketosis, diabetic ketoacidosis and hyperglycaemic hyperosmolar state. This makes fasting in Ramadan particularly challenging for those Muslims with diabetes. Here, we discuss the implications of fasting in Ramadan during the COVID‐19 pandemic and make recommendations for those with diabetes who wish to fast.

Muslims around the world fast for the holy month of Ramadan. This involves abstaining from food and drink from dawn (suhoor) to dusk (iftar), for the entire month, and is fundamental to the faith as one of the five pillars of Islam. While fasting is considered compulsory for all adult Muslims, there are exemptions for those who are pregnant, lactating, travelling, or have any acute or chronic health conditions (where fasting may place them at risk of ill-health). Although this means fasting is not mandatory for Muslims with diabetes, many will still choose to fast for spiritual as well as social and cultural reasons; the Epidemiology of Diabetes and Ramadan (EPIDIAR) survey of over 12,000 people with diabetes in 13 Islamic countries, indicated that approximately 43% of people with type 1 diabetes mellitus and 79% of people with type 2 diabetes mellitus fast during Ramadan [1] . Similarly, Muslims who develop any acute illness, including COVID-19, are exempt from fasting, but may choose to do so regardless. As COVID-19

can present with a variety of symptoms, which range in severity from mild to life-threatening, it may be difficult for people with diabetes who are fasting and become symptomatic to assess whether they are well enough to continue their fast or not.

Refraining from eating and drinking from sunrise to sunset has health implications for all observing this spiritual practice, but can significantly impact those with diabetes, placing them at higher risk of complications such as hypoglycaemia, hyperglycaemia and ketoacidosis, and cardiovascular complications [2] , which may be exacerbated by COVID-19. The World Health Organisation (WHO) has recently released general guidelines on fasting in Ramadan during the COVID-19 pandemic [3] . However, it is vital, for healthcare professionals to be equipped to specifically counsel people with diabetes on ensuring appropriate food and fluid intake, monitoring of blood glucose and awareness of when to break their fast if necessary. The South

Asian Health Foundation has recently published guidelines for healthcare professionals regarding the management of people with diabetes who wish to fast for Ramadan, based on current evidence [4] . However, there is a need to update the advice on how best to support people with diabetes who intent to fast during Ramadan, in the midst of the COVID-19 pandemic.

COVID-19 is a severe acute respiratory distress syndrome caused by the SARS-CoV-2 novel coronavirus [5] . The rapid spread of this highly contagious disease has been declared a global public health emergency by the World Health Organisation (WHO) [6] and is straining healthcare Accepted Article systems and economies worldwide. While populations around the world are being affected, recent publications have identified certain risk factors associated with more severe disease; these factors include increasing age, male sex and comorbidities such as cardiovascular disease, hypertension and diabetes [7] . The UK Intensive Care National Audit and Research Centre (ICNARC) suggest that the BAME (Black, Asian and minority ethnic) community, which includes a considerable Muslim population, is at a disproportionate risk of developing severe disease, requiring ventilation [8] . While the reasons for this increased risk are currently unclear, factors ranging from lower socioeconomic background, intergenerational living and congregational prayers may be implicated, along with an increased burden of underlying cardiovascular disease [9] and diabetes [10] , as well as possible genetic mechanisms including angiotensin converting enzyme (ACE) polymorphism [11] .

In order to address the concerns of healthcare professionals and people with diabetes fasting for Ramadan, the South Asian Health Foundation here presents updated guidance tailored to the COVID-19 pandemic.

The challenges of fasting for people with diabetes, during the COVID-19 pandemic There is increased risk of hypoglycaemia, hyperglycaemia, diabetic ketoacidosis (DKA), dehydration and thrombosis in people with diabetes who are fasting during Ramadan [1] .

Concurrent COVID-19 may precipitate these complications or exacerbate them. The recent evidence emerging from the United Kingdom in the midst of the COVID-19 pandemic, as well as published data from China and Italy, indicates that people with diabetes have an increased risk of the infection and manifest a severe disease state, with systematic reviews suggesting that diabetes is associated with a two-fold higher risk of severe COVID-19 disease and mortality [16] .

It has been proposed that inadequate glycaemic control may contribute to this increased risk. In people presenting to UK hospitals with COVID-19, there has been a greater incidence of DKA, hyperglycaemic hyperosmolar state (HHS) and euglycaemic ketoacidosis, even in those who

This article is protected by copyright. All rights reserved have type 2 diabetes, or are insulin naïve. This appears to be a result of severe insulin resistance, starvation ketosis and/or dehydration (or a combination of all three). COVID-19 may, therefore, precipitate the complications seen in people with diabetes who fast. In addition, it has been suggested that dehydration and acute kidney injury (AKI) increase the severity of COVID-19, along with hypercoagulability leading to thrombotic events. Thus, the complications of fasting during Ramadan could be implicated in the worsening of COVID-19. It is important to take these factors into consideration while advising people with diabetes about fasting during Ramadan in the midst of the COVID-19 pandemic.

The South Asian Health Foundation has recently published the risk stratification for people with diabetes intending to fast during Ramadan [4] . As a result of the COVID-19 pandemic, additional risk factors should be considered when assessing an individual's risk of complications during fasting. People with diabetes experiencing symptoms of COVID-19 [12] , such as high fever, a new, persistent dry cough or anosmia [13] should be considered at high risk for developing cases should also be made aware that they are at increased risk of complications should they contract the infection, and that fasting should be undertaken with caution -however, this factor alone is quantified as low risk.

We recommend that people in the high risk category during the current COVID-19 pandemic must not fast. Those in the moderate risk category should not fast. People in the low risk should take adequate precautions if they choose to fast. This is summarised in Figure 1 .

For people with diabetes choosing to fast for Ramadan, frequent blood glucose monitoring is imperative to mitigate the risk of complications, particularly with the high incidence of COVID-19

infection. It is well-established that concurrent infection, including COVID-19, may precipitate hyperglycaemia, DKA and dehydration, hypoglycaemia, or alter their presentation [14] . We recommend, therefore, that people with diabetes; check their capillary blood glucose at least four times a day during fasting -at suhoor time, two hours into the fast, just before breaking the fast at iftar and two hours after breaking the fast. People with diabetes who demonstrate COVID-19 symptoms; check their blood glucose every 4-6 hours, along with ketone levels. Additionally, if they experience any symptoms of hypo-or hyperglycaemia or become unwell, they check their blood glucose.

When to break the fast People with diabetes are advised to break their fast if they develop any symptoms of hypoglycaemia, hyperglycaemia, dehydration, or other acute illness. While, people with diabetes need to break the fast for any acute illness, it needs to be emphasised that development of symptoms of COVID-19 during fasting requires prompt breaking of the fast. If blood glucose during fasting is <3.9 mmol/L or >16.6 mmol/L, people with diabetes need to break their fast, whether or not they have any symptoms [13] . For those using insulin or sulfonylureas, the fast sbe broken if blood glucose is <3.9 mmol/L at the beginning of the fast [15] .

Managing people with type 1 diabetes who are fasting during the COVID-19 pandemic.

We recommend that any people with type 1 diabetes experiencing symptoms of COVID-19 [13] do not fast. It is also highly advisable that people with type 1 diabetes if there are high rates of transmission of COVID-19 in their country. If people with type 1 diabetes choose to fast during this pandemic, they need to check their capillary blood glucose at least four times a day. If people with type 1 diabetes who are fasting develop COVID-19 symptoms, they should break their fast and check their blood glucose and ketones every 4-6 hours. Alongside these measures, people with type 1 diabetes should ensure adequate fluid intake of 2-3L of water or unsweetened beverages during non-fasting hours, and close adherence to infection control measures including frequent hand-washing and social distancing.

This article is protected by copyright. All rights reserved Managing people with type 2 diabetes who are fasting during the COVID-19 pandemic.

People with type 2 diabetes are at risk of complications from both fasting and COVID-19, and therefore we recommend they need to follow guidelines closely if they choose to fast. For these people, the focus is on avoiding hypoglycaemia during the fast and post-prandial hyperglycaemia, as well as avoiding weight gain and dehydration, and, as for all people, reducing the risk of acquiring COVID-19 infection. It is important for people with diabetes to adhere to social distancing guidance to reduce their risk of infection, including avoiding congregational prayers at the mosque.

People with type 2 diabetes should follow an individualised nutrition plan, taking into account their age, cultural norms and comorbidities. At mealtimes, people with diabetes should incorporate foods with a low glycaemic index, and ensure a balanced macronutrient profile, avoiding the large meals containing highly processed carbohydrates and sugars that are often seen at iftar. People with diabetes need to eat their suhoor meal as late as possible, to avoid hypoglycaemia towards the end of the fast. This is especially important during prolonged fasts.

To avoid dehydration, people with type 2 diabetes need to drink 2-3 litres of water or unsweetened beverages over the course of the non-fasting hours, particularly as any concurrent COVID-19 infection can be worsened by dehydration and hypovolaemic acute AKI. For many Muslims, physical activity is reduced during Ramadan [16] , particularly voluntary exercise (compared to physical labour for work, for example), as a result of altered sleeping patterns, lethargy associated with fasting and increased priority of socio-religious practices. However, performing light exercise may be beneficial in avoiding weight gain, maintaining fitness and improving mood and sleep [17] ; this psychological benefit is especially important in light of social isolation measures and financial uncertainty leading to low mood and increased anxiety as a result of the COVID-19 pandemic [18] . The government-imposed social distancing measures may make exercising more challenging, but people with diabetes can take their permitted daily exercise, while maintaining social distancing and infection control measures. Exercise may be performed in the home or in the garden to reduce exposure to other members of the public. It is important, however, to avoid strenuous exercise while fasting, particularly in hot weather, due to

This article is protected by copyright. All rights reserved the risk of dehydration, and preferential to avoid exercise in the last few hours before iftar, owing to the increased risk of hypoglycaemia at this time. If people with type 2 diabetes feel unwell during or after exercise, they should check their blood glucose and consider breaking the fast if any of the above circumstances apply.

We recommend the following advice with regards to medication during fasting, in the COVID-19 pandemic.

Currently, there is little information specifically pertaining to the incidence of hypoglycaemia during fasting in people with diabetes using metformin alone. However, the risk of hypoglycaemia is considered low, as metformin augments insulin sensitivity rather than increasing insulin secretion [19] . People with type 2 diabetes taking metformin therefore do not require any dose modification, and can take their lunchtime dose at iftar time. People with stable diabetes on metformin should be able to fast safely, but need to ensure adequate fluid intake. If people with type 2 diabetes experience any symptoms of dehydration, or of infection with COVID-19, or are admitted to hospital while fasting, they should break the fast. Healthcare professionals should also stop metformin if people with diabetes develop dehydration or COVID-19 symptoms, or if the eGFR is rapidly dropping, due to the risk of AKI [20] .

Sulphonylureas increase the risk of hypoglycaemia in people with diabetes, as they stimulate the secretion of insulin. It is recommended that long-acting sulphonylureas like glibenclamide should be avoided while fasting during Ramadan, as they have a greater risk of hypoglycaemia. Second generation sulphonylureas (gliclazide and glimepiride) however, can still be used. The once-daily dose needs to be taken at iftar. For people with stable diabetes, who are taking sulphonylureas twice daily, the suhoor dose needs to be reduced while the iftar dose remains the same. People with diabetes taking sulphonylureas who develop COVID-19 symptoms need to continue their medications, check their blood glucose levels more frequently and maintain adequate hydration [20] .

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Studies have demonstrated the safety of DPP-4 inhibitors in people with diabetes who are fasting during Ramadan. These agents carry a minimal risk of hypoglycaemia, and require no dose adjustment for fasting. In people with diabetes who take DPP-4 inhibitors and develop symptoms of COVID-19, it is recommended to continue with their medication, check blood glucose levels regularly and maintain adequate hydration.

SGLT-2i have emerged as an important therapeutic option in reducing the risk of cardiovascular and renal disease in people with type 2 diabetes. They also have a lower risk of hypoglycaemia and require no dose adjustment for fasting in Ramadan. They are effective in reducing weight and blood pressure [21] . One of the risks associated with SGLT-2i is dehydration, particularly in hot climates. Furthermore, the Food and Drug Administration Drug Safety Communication warns of the risk of euglycaemic ketoacidosis [22] . Current reports regarding COVID-19 suggest that people with dehydration and AKI are at increased risk of developing severe disease. There have been many reports of people with type 2 diabetes and COVID-19 presenting with ketoacidosis, regardless of the use of SGLT-2i. Hence, extra care should be taken when using this class of drugs in people with diabetes fasting for Ramadan. Table 1 summarises the concerns and practical tips on the use of SGLT2 inhibitors during Ramadan fasting in people with type 2 diabetes, in the COVID-19 pandemic.

We recommend that SGLT-2i should be continued in select people with diabetes, with all necessary precautions taken. If people with diabetes develop symptoms of COVID-19, they stop their SGLT-2 inhibitors, ensure adequate hydration, check their blood glucose levels frequently and follow "sick day rules".

Thiazolidinediones are considered safe for use by people with type 2 diabetes fasting for Ramadan, as they are not directly associated with hypoglycaemia [19] . Recently, a hypothesis has emerged, suggesting that thiazolidinediones, along with other medication classes such as

This article is protected by copyright. All rights reserved angiotensin-converting enzyme (ACE) inhibitors and angiotensin II Type-I receptor blockers (ARBs), and ibuprofen, may lead to the increased expression of angiotensin-converting enzyme-2 (ACE-2 ) receptors [23] . As the novel SARS-CoV-2 coronavirus interacts with the ACE2 receptor to facilitate transmission [24] , this group proposed that the increased expression of ACE-2 receptors may augment infection with COVID-19, increasing the risk of people treated with the aforementioned drugs developing severe COVID-19. It should be reinforced that this is a hypothesis based on retrospective data showing increased incidence of severe COVID-19 in people with hypertension and diabetes, groups of people prescribed ACE-inhibitors, ARBs and thiazolidinediones. There is currently a lack of direct evidence to support the discontinuation of GLP-1RA are considered safe drugs for people with diabetes to continue using during Ramadan, due to their low risk of hypoglycaemia [19] . Nausea and vomiting are well-established sideeffects of GLP-1RA [25] , meaning dehydration is a hypothetical risk with use of these medications. However, studies of GLP-1RA in Ramadan have shown low risk of dehydration or infection [26] . Other benefits of GLP-1RA include increased satiety; this reduces the likelihood of overeating once the fast is broken, which may avoid post-prandial hyperglycaemia and weight gain. Data from the ICNARC indicates that many people admitted to ITU with severe COVID-19 are overweight or obese; hence GLP-1RA may be a beneficial therapeutic option [8] . GLP-1RA are safe to use for people with type 2 diabetes fasting for Ramadan, including if they develop mild symptoms of COVID-19, but adequate hydration and regular checking of blood glucose is required. If people with diabetes develop severe COVID-19 symptoms, requiring hospital admission, or develop AKI, reduced appetite or gastrointestinal symptoms, the GLP-1RA should be stopped.

This article is protected by copyright. All rights reserved Insulin increases the risk of hypoglycaemia significantly during Ramadan fasting, so doses must be adjusted and individualised on the basis of baseline glycaemic control, diet, exercise, occupation and blood glucose monitoring, especially in older people. People with diabetes need to monitor their blood glucose levels regularly, at least four times a day; we recommend at suhoor time, two hours into the fast, just before breaking the fast at iftar and two hours after breaking the fast, as well as if they experience any symptoms of hypo-or hyperglycaemia. If blood glucose are <3.9 mmol/L or >16.6 mmol/L at any time during the fast, people with diabetes should break the fast. If blood glucose levels are <3.9 mmol/L at the time of suhoor, they should not undertake the fast. A recent study evaluating the effect of optimum diabetes care on the safety of fasting in Ramadan in adults with type 2 diabetes found no increased safety risks in those treated with insulin, when Ramadan-focused education and medical advice for treatment adjustment was provided before Ramadan, alongside flash glucose monitoring for the duration of the fasting period [27] . If people with diabetes develop COVID-19 symptoms during fasting, they need to break the fast and check their blood glucose levels, and ketones. They should follow the "sick day rules" that advise continuing the dose of insulin, monitoring blood glucose levels regularly and maintaining adequate fluid intake and diet. If people with diabetes are suffering from diarrhoea and vomiting, they need to take oral fluids; if blood glucose levels are low, these fluids should contain sugar, and if high, should be unsweetened.

For people with diabetes fasting in Ramadan, basal insulin is the preferred initial formulation. For long acting insulins, the dose should be reduced by 20% and taken at iftar. In people using a basal-bolus regime, the lunch dose of rapid-acting insulin need to be omitted and the remaining two doses need to be taken with meals at suhoor and iftar. In people on mixed insulin, taking a higher dose of insulin in the morning and lower dose in the evening, the dosing should be switched during fasting so that the lower dose is taken at suhoor and the higher dose at iftar. In some cases, the higher dose may be reduced.

The recommendations for all glucose-lowering therapies during Ramadan in the COVID-19 pandemic is summarised in Table 2 .

The management of medications in people with diabetes fasting during Ramadan

This article is protected by copyright. All rights reserved When people with type 1 or type 2 diabetes are admitted to the hospital acutely unwell, with evidence of dehydration or AKI, the following classes of medications need to be stopped:  If evidence of AKI, or dehydration, consider stopping ACE-inhibitors and ARBs.

 Avoid using Non-Steroid Anti-Inflammatory Drugs (NSAIDs).

 Be aware that people with diabetes (both type 1 and type 2 diabetes) requiring hospital admission may present with DKA, HHS, or euglycaemic ketoacidosis.  All people with type 1 and type 2 diabetes admitted to hospital will require ketones to be checked regularly, along with blood glucose monitoring.

 It appears in those with COVID-19 and diabetes, the development of DKA and HHS is associated with significant insulin resistance and therefore, these people may require up to 20 units of insulin per hour [20] . In addition, fluid replacement with DKA/ HHS protocols should be individualised and may require more cautious replacement in those at risk of acute respiratory distress syndrome or COVID myocarditis.

These guidelines from the South Asian Health Foundation (UK) are based on current consensus and initial evidence of people with COVID-19 and diabetes. However, gaps still exist in the management of diabetes during this pandemic, which could be the focus for future research (Table 3) . 

This article is protected by copyright. All rights reserved 

A populationbased study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care

A systematic review on efficacy and safety of the current hypoglycemic agents in patients with diabetes during Ramadan fasting

Safe Ramadan practices in the context of the COVID-19

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A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence

The World Health Organisation

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China

Trends for coronary heart disease and stroke mortality among migrants in England and Wales, 1979-2003: slow declines notable for some groups

Chapter 3: trends in morbidity and risk factors

Accepted Article This article is protected by copyright. All rights reserved

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Symptoms and what to do -Coronavirus (COVID-19) -NHS

In patients of COVID-19, what are the symptoms and clinical features of mild and moderate cases?

Oxford COVID-19 Evidence Service Team Centre for Evidence-Based Medicine

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Physical activity -the Holy Grail of modern medicine?

The outbreak of COVID-19 coronavirus and its impact on global mental health

Guidelines for managing diabetes in Ramadan

COVID:Diabetes): Front Door Guidance

Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with Type 2 diabetes. Diabetes Care

FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections | FDA

Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

Adverse Effects of GLP-1 Receptor Agonists

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Impact of optimum diabetes care on the safety of fasting in Ramadan in adult patients with Type 2 diabetes mellitus on insulin therapy

Accepted Article