Time-Restricted Eating Tightens Glycemic Control in Patients With Metabolic Syndrome

For people with metabolic syndrome, a personalized lifestyle intervention that promotes time-restricted eating (TRE) during an 8- to 10-hour window “modestly improves” glycemic regulation over standard-of-care pharmacotherapy and nutritional counseling at 3 months, results from the TIMET randomized study suggest.

“We are seeing multiple cardiometabolic benefits with TRE that go beyond just weight loss,” Pam R. Taub, MD (University of California, San Diego), senior author of the new report, told TCTMD via email. She highlighted the 0.01% greater decline in HbA1c for the TRE versus control groups as “not trivial,” noting that it’s akin “to what was seen in the landmark Diabetes Prevention Study, in which a similar reduction in prediabetes led to a 58% decrease in the future development of diabetes.”

Evidence from experimental, mechanistic, and randomized studies of approaches to changing the timing of food consumption is mixed when it comes to impacts on weight loss and other factors, such as cardiometabolic risk factors. Earlier this spring, for instance, an observational study controversially suggested time-restricted eating might even raise CV risk—its many critics, including Taub, cited confounding as the reason for the counterintuitive result.

Here, the TIMET investigators focused on a specific subgroup: patients with elevated fasting glucose characteristic of prediabetes or an HbA1c level at or just below the threshold for diabetes.

“Metabolic syndrome, especially when paired with prediabetes, represents a critical tipping point in which the risk for developing Type 2 diabetes and heart disease is greatly increased,” she explained, pointing out that lifestyle interventions such as TRE could meaningfully impact the trajectories of patients’ overall health and reduce their future risk of type 2 diabetes.

People “with metabolic syndrome have other parameters, such as elevated cholesterol and high blood pressure, that can also improve with TRE,” said Taub.

The new TIMET data were published online recently in the Annals of Internal Medicine.

Benjamin Horne, PhD (Intermountain Medical Center, Salt Lake City, UT, and Stanford University, CA), commenting for TCTMD, said the study is unique in that it doesn’t use weight loss as the primary outcome. That said, Horne added, it’s not surprising to see the reduction in HbA1c, since losing weight can lead to “many changes that are positive for cardiovascular health.”

Another positive of TIMET is the focus on a population that’s on the cusp of change, which opens the door to prevention, he observed. “Intermittent fasting, I think, speaks to the population where some of the risk factors are abnormal or on their way to being abnormal: you don't have disease yet and you can use fasting to pull people back from the brink. . . . It’s exciting from that standpoint.”

The ”million dollar question,” said Horne, is exactly what drives the gains seen with TRE. Some data have indicated that “you get some benefit in controlling the spikes and troughs of blood sugar on a daily basis if you're doing time-restricted eating in a certain way,” he explained, though it may be that shifting to a different schedule leads people to consume fewer calories or that weight loss alone makes an impact.

For most patients, TRE is safe and presents little risk of harm, he noted, so may be worth a try, though he cautioned that when in doubt it’s worth first checking with a doctor.

Importantly, “fasting is free of charge,” with no financial cost or need for a prescription, Horne stressed. “All people, regardless of sex, race, ethnicity, socioeconomic status: everyone has access to the benefits of fasting if they just choose to do it.”

Better Glycemic Control in 3 Months

Led by Emily N.C. Manoogian, PhD (The Salk Institute for Biological Studies, La Jolla, CA), Taub and colleagues enrolled 122 adults with metabolic syndrome who had a body mass index (BMI) of 25-41 kg/m² plus elevated fasting glucose suggesting prediabetes (5.56-6.95 mmol/L, or 100-125 mg/dL) or elevated HbA1c (5.7%-7.0%).

The researchers randomized the participants to standard of care nutritional counseling alone or with the addition of TRE for 3 months. The dietary intervention consisted of a personalized 8- to 10-hour window of time-restricted eating, with at least a 4-hour reduction in the eating window compared with baseline; the specific schedule was designed for each person’s baseline eating habits as well as their usual sleep time. Outside of the eating window, they were only allowed water and prescribed medications.

Both groups used the smartphone app, myCircadianClock, to track their dietary intake. The software provided daily prescheduled messages, including blog posts, with guidance on physical activity, sleep, stress, diet, and prompts to record eating times.

Ultimately, 108 of the 122 individuals completed the 3-month study. Mean age was 59 years, 52% were women, and mean BMI was 31.22 kg/m². Baseline HbA1c levels were similar between the two groups, as was medication use for type 2 diabetes: 6% took metformin for prediabetes and 48% for hyperlipidemia. Nearly 70% were on at least one drug for cardiometabolic health, a category that included antihypertensives.

Adjusting for age, HbA1c decreased by 0.12% between baseline and 3 months with time-restricted eating, while controls saw their HbA1c decrease by only 0.02% (between group difference of 0.10%; percent change -1.7%).

The amount of glycemic variability in the TRE group was less than in controls, both within the day and across days. Because high variability signals prediabetes and is a key aspect of type 2 diabetes mellitus, the investigators note, the short-term impact of TRE “may have implications for improved long-term cardiometabolic health outcomes beyond decreased HbA1c.”

The patients assigned to TRE on average had a 3.3-kg decrease in body weight at 3 months, compared with a 1.32-kg decrease among controls. They also saw greater reductions in BMI, percentage of body fat and trunk fat, and total fat mass. Yet there were no differences in total lean mass/skeletal muscle mass or bone mineral content, Taub pointed out, “which indicates that TRE is a safe lifestyle strategy and does not cause sarcopenia.”

The intervention group also saw a greater reduction in LDL cholesterol as well as positive but nonsignificant trends in other cardiometabolic variables.

The researchers note several limitations to their study, including its short duration, the self-reported dietary details, and potential for overlapping factors (eg, biological sex and changes in adiposity) to impact outcomes.

TRE in the Clinic

One question is how the TRE strategy fits into today’s practice given the surging popularity of GLP-1 receptor agonists.

These medications “are a great class of drugs that result in significant weight loss, [but] they are expensive, so access to these drugs is still limited for a majority of the population. Evidence-based lifestyle strategies are also needed that can synergize with drugs,” Taub said. “In my clinical practice, many patients do both TRE and GLP-1 RAs.”

At the start of TRE, “I tell my patients to first start by cutting out late-night snacks and then try fasting for 12 hours after dinner and to gradually increase to 14 hours of fasting,” said Taub. “Everyone gets one ‘cheat day’ and for some reason if they are not able to adhere to it due to travel, etc, it is easy to pause and come back to TRE.” With adoption of the new dietary pattern, patients taking antihypertensives may need adjustments to dosing, she added.

Horne pointed out that diabetes medications, too, might need to be tweaked with eating times in mind, to avoid the potential for hypoglycemia.

Additionally, while TRE is a “fairly low impact regimen” for most people, it’s important to remember that “some of the benefits of fasting occur because fasting stresses the body,” he noted. “And so if someone's frail or older or has multiple comorbidities or recent adverse cardiovascular events or so forth, they probably need to consult with their physician and may not qualify.”

Overall, the literature is “pretty convincing” that TRE offers positive effects on cardiac risk factors, but there remains the uncertainty of whether these changes prevent or delay disease, Horne said. He called for larger, longer studies as well as research comparing TRE with different fasting durations.

TIMET has a relatively short intervention of 3 months, Horne highlighted. “That's kind of the acute benefit phase . . . From a cardiovascular perspective, 3 months is not long enough to prevent coronary disease, the onset of heart failure, or even necessarily the onset of diabetes.”

It’s also unknown, Taub acknowledged, how the 0.1% reduction in HbA1c would evolve over time—growing larger, smaller, or staying the same—with a longer intervention, though she said that even if it held steady, this would be enough to reduce future diabetes risk. Ongoing research also is looking at TRE’s impact in type 2 diabetes, postural orthostatic tachycardia syndrome, and microalbuminuria, said Taub.