Intermittent Fasting 'Not Benign' for Patients With Diabetes

Marlene Busko

July 07, 2020

"Patients with type 2 diabetes should consider intermittent fasting carefully" and "not undertake it without the involvement of their physician," stress the authors of a new viewpoint published online July 2 in JAMA.

This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.

Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.

The viewpoint's lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, Utah, and Stanford University, California, expanded on the issues in a podcast interview with JAMA Editor-in-Chief Howard C. Bauchner, MD.

Asked if he would advise intermittent fasting for patients with type 2 diabetes, Horne replied that he would recommend it, with caveats, "because of the safety issues — some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes."

"Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations," he continued, but "the big issue" is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.

Horne said he likes to give patients options. "I've met quite a number of people who are very behind time-restricted feeding — eating during a 6- to 8-hour window," he said. "If they are able to stay on it, they tend to really love it."

The most popular regimen that results in some weight loss is fasting for 24 hours — with or without a 500-calorie meal — on two nonconsecutive days a week, the so-called 5:2 diet.

And "as someone who's in cardiovascular research," Horne added, "the one that I'm thinking for long-term is once-a-week fasting for a 24-hour period."

Intermittent Fasting: Less Safe Than Calorie Restriction in Diabetes?

Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Horne and colleagues write.

Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes "that are as yet untested or unproven," they add. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy,” they stress.

Thus, they examined the existing evidence for the health effects and safety of intermittent fasting — defined as time-restricted feeding, or fasting on alternate days or during 1 to 4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days — in patients with type 2 diabetes.

They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.

Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18 to 20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3 to 4 days a week for 7 to 11 months; 4 days a week for 12 weeks; and 17 days in 4 months.

They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.

But this "heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction," Horne and colleagues observe.

Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.

Only one study explicitly compared intermittent fasting with caloric restriction, and its finding, "that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising," the authors write.

However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs –0.5% for caloric restriction).

The major implication, according to the viewpoint authors, is that "intermittent fasting may be less safe than caloric restriction although approximately equivalently effective."

"Therefore," they summarize, "until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study — and the limited other high-quality data — suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety."

Consider Continuous Glucose Monitoring to Detect Glycemic Variability

Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Horne and colleagues point out.

"Studies have raised concern that glycemic variability leads to both microvascular (eg, retinopathy) and macrovascular (eg, coronary disease) complications in patients with type 2 diabetes," they caution.

Therefore, "continuous glucose monitoring should be considered for studies of...clinical interventions using intermittent fasting in patients with type 2 diabetes," they conclude.    

Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.  

JAMA. Published online July 2, 2020. Viewpoint

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