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03-31-2022 | Diet | Hot topic review | Article

Fasting and people with diabetes

Author: Eleanor McDermid

medwireNews Hot Topic Reviews provide up-to-date overviews of fast-moving areas of research in order to help healthcare providers keep abreast of the latest developments that may influence patient care.

Diets for weight loss that incorporate an element of fasting are enjoying current popularity among the public and in the mainstream media, prompting many people, including those with diabetes, to try them. In addition, large numbers of people with diabetes wish to fast in order to fully participate in religious festivals such as Ramadan and Yom Kippur.

But such diets carry inherent risks for people with type 1 or type 2 diabetes, and there is only limited research into fasting specifically in these groups.

How do we define fasting?

Fasting is generally thought of as the voluntary avoidance of all calories, and often also fluids, for a defined period as is practiced during some religious festivals.

By contrast, the definition of a fasting diet followed for health reasons can vary widely, including in the medical literature. But broadly speaking these diets fall into two categories.

The first is intermittent fasting diets, in which either water only or a very small number of calories, often around 500, are allowed during a day; this can be on alternate days, for example, or on 2 days per week (the 5:2 diet). The second category is time-restricted eating, where calories are not restricted but adherents do all of their daily eating within a small window, such as 6 or 10 hours, and consume only water or other calorie-free fluids for the remainder of the 24 hours.

In addition, some diets that are effectively very-low-calorie diets have been described as “fasting-mimicking diets” by researchers.

Does fasting have any advantages over standard calorie restriction?

In terms of research endpoints, diets that incorporate an element of fasting have no advantage over simple low-calorie diets.

Most randomized trials to date in people with type 2 diabetes have allowed approximately 500 calories/day for a period of 5 consecutive days or longer, with a smaller number exploring an intermittent fasting schedule. These trials generally reported significantly greater bodyweight reductions when the control condition was as-usual eating, but not when it was a conventional calorie-restricted diet (see meta-analysis by Borgundvaag et al 2021). A common pattern was that people with a higher baseline BMI benefited more than those with a lower bodyweight.

Likewise, glucose metabolism and lipid profiles were not improved more by a fasting diet than a conventional low-calorie diet. A trial in metabolically healthy people with obesity showed significant reductions in insulin levels and insulin resistance with a fasting diet, but again by no more than induced by a standard low-calorie diet.

So why might a person with diabetes opt to fast?

As previously mentioned, one major driver of the desire to fast is the wish to fully participate in religious festivals. Although people with conditions such as diabetes are generally exempt from the requirement for religious fasting, the Diabetes and Ramadan (DaR) Global survey of1483 people with type 1 diabetes in 13 countries found that 71% chose to fast for Ramadan 2021.

From a weight-loss perspective, diets with an element of fasting offer an alternative approach to conventional low-calorie diets, which is a hugely important point, given that the success of any diet is largely determined by how long people stick to them. Fasting diets have the advantages of simplicity, particularly in the case of time-restricted eating for people who dislike constant calorie counting; and flexibility, in regimens such as intermittent fasting, where the fasting days can be moved to fit around people’s professional and social lives.

Weight loss can be very rapid with very-low-calorie or fasting-style diets, and recovery of the beta cells with significant weight loss has been reported in people with type 2 diabetes in DiRECT and with a fasting diet in mouse models of both type 1 and type 2 diabetes. In addition, the one study of fasting in people with type 1 diabetes that looked beyond safety issues identified an improvement in quality of life during 7 days of fasting.

For people with type 2 diabetes, the very high prevalence of overweight and obesity in this population makes the potential benefits of fasting obvious. Indeed, the DaR Alliance guidelines on supporting people with diabetes to fast during Ramadan encourage physicians to view the month as a springboard for initiating dietary change and weight loss in their patients with type 2 diabetes.

And although people with type 1 diabetes represent, on average, a slimmer population, recent research from the USA shows that the prevalence of obesity in this group is equivalent to that in the general population, indicating a need for effective weight-loss strategies. Diets with elements of fasting could therefore benefit this population – as long as the risks can be managed.

What are the risks of fasting for people with type 1 diabetes?

For people with type 1 diabetes, the main risks of fasting are hypoglycemia and hyperglycemia, plus the theoretical risk for acidosis resulting from the build-up of ketones. Other considerations include the effects of high glycemic variability on the risk for micro- and macrovascular complications, and the potential for fasting to trigger disordered eating, particularly in people with a history of these conditions.

The problem with accurately gauging such risks in people with type 1 diabetes is that very little of the research published to date reflects real-world use of fasting diets. All formal studies of fasting have addressed safety, demonstrating the feasibility of fasting for up to 7 consecutive days, but all in a highly controlled, usually inpatient environment involving a small number of participants.

A large amount of data come from observational studies of religious fasting. However, even this represents an unusual situation. In Ramadan, for example, participants withhold all food and drink between sunrise and sunset, and the two meals they do have can be large and the post-sunset meal (Iftar) may feature more sweets than would be usual.

Data from Ramadan 2021 show that approximately 60% of people with type 1 diabetes experienced hypoglycemia and around 45% had hyperglycemia. Most instances occurred during the first 7 days of Ramadan, and 6.8% of people required emergency medical treatment for these complications.

Managing the risk

While type 1 diabetes is itself regarded as a risk factor for acute complications during fasting, experts writing in The Lancet Diabetes & Endocrinology recently argued for a more nuanced approach.

Sufyan Hussain (King’s College London, UK) and colleagues consider people at low/moderate risk to be those with well-controlled glucose levels and the ability to frequently check them, good awareness of hypoglycemia symptoms, and in receipt of regular specialist care. They should also have been educated in managing their blood glucose during Ramadan and be prepared to break their fast should the need arise. These people are eligible to undertake fasting with medical support.

People in higher-risk categories are those with poorly controlled, unstable, or recently diagnosed diabetes; diabetic complications; acute illness; or impaired hypoglycemia awareness. Other people who the authors say should not fast are pregnant women, people undertaking hard manual labor or long periods of driving, and those who are taking adjunct sodium-glucose cotransporter (SGLT)2 inhibitors – the last because of the increased risk for ketoacidosis.

When people with type 1 diabetes do attempt a fast, one key issue is preemptive reduction of insulin dose. In one study of young people fasting for Yom Kippur, the main determinant of success was reducing their insulin dose by around two-thirds; those forced to break their fast had been more cautious in their dose reduction. Other key factors, as mentioned, are frequent monitoring of glucose levels and being prepared to break the fast if necessary to treat hypoglycemia.

What are the risks of fasting for people with type 2 diabetes?

People with type 2 diabetes face similar risks as those with type 1 diabetes, although for many the risk may be less due to a greater ability to produce endogenous insulin. In one trial of intermittent fasting in people with type 2 diabetes, participants had double the risk for experiencing hypoglycemia during their 2 days of fasting each week relative to their 5 days of eating as usual. Nevertheless, the overall rate was low, at an average of 1.4 events during the 12-week study.

On the other hand, people with type 2 diabetes are often taking a complex array of medications. Although insulin and sulfonylureas are most usually associated with hypoglycemia risk, Benjamin Horne (Intermountain Medical Center Heart Institute, Salt Lake City, Utah, USA) and co-authors of a 2020 opinion article in JAMA stress: “No antidiabetic medication can be assumed to be completely safe from causing hypoglycemia in a person undertaking intermittent fasting.”

A previous article from two of the same authors, in Nutrients, offers advice on managing medications during a fast. This includes:

  • No action (eg, for metformin and weekly glucagon-like peptide-1 receptor agonists);
  • Skip the dose to reduce costs (eg, for dipeptidyl peptidase 4 inhibitors and SGLT2 inhibitors);
  • Reduce or omit to avoid hypoglycemia (eg, for sulfonylureas and basal/prandial/combination insulins).

This advice was published in 2019 and Horne confirms that their advice remains similar at the time of writing (2022). But he issues a caution that specific groups of people with type 2 diabetes should be advised against fasting. These are people who have chronic kidney disease, an organ transplant, dementia, or an eating disorder, as well as those who are immunodeficient, younger than 18 years or old and/or frail, pregnant or breastfeeding, or undergoing cancer treatment.

In reference to medication classes, Horne also notes the existence of “new evidence that fasting has similar effects on human physiology as SGLT-2 inhibitors.”

Both interventions “substantially reduce circulating levels of blood sugar (glucose) and thereby induce the use of ketones and fatty acids for energy,” he explains, adding that they also affect the human growth hormone–insulin-like growth factor-1 axis, induce natriuresis, and may reduce anemia.

“Because of these findings and similarities, it is uncertain whether people who are using SGLT-2 inhibitors will obtain further health benefit from fasting,” Horne says. “Thus we are studying this in additional prospective research studies.”

In the meantime, he continues to suggest that people can skip their SGLT2 inhibitor dose on fast days – except for those who are practicing time-restricted eating, who should continue to take it, but ensure that they remain well hydrated.

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