A new BWH study may help explain why glucose tolerance—or the ability to regulate blood sugar levels—is lower at dinner than at breakfast for healthy people. It may also provide clues as to why shift workers have an increased risk of diabetes, which is caused by high blood sugar and can lead to serious health problems.

In a highly controlled study of 14 healthy individuals, a team led by BWH researchers measured the independent influences of behavioral factors—such as meal time and sleep/wake cycle—and the body’s internal clock, and how the misalignment between these behaviors and the body clock can affect a person’s ability to control blood sugar. The team reported its findings, with implications for shift workers and for the general public, earlier this week in Proceedings of the National Academy of Sciences.

“Our study underscores that it’s not just what you eat, but also when you eat that greatly influences blood sugar regulation and that has important health consequences,” said co-author Frank Scheer, PhD, associate neuroscientist in the Division of Sleep and Circadian Disorders and departments of Medicine and Neurology at BWH. “Our findings suggest that the circadian system strongly affects glucose tolerance, independent from the feeding/fasting and sleep/wake cycles.”

In the study led by Scheer and co-author Christopher Morris, PhD, an instructor of medicine in the Division of Sleep and Circadian Disorders, participants took part in two protocols. In the first, participants had breakfast at 8 a.m. and dinner at 8 p.m. and slept at night. In the second, participants’ schedules were reversed by 12 hours, with breakfast at 8 p.m. and dinner at 8 a.m., and they slept during the day. The meals were identical in both protocols. The research team measured levels of glucose and insulin at 10-minute intervals after each meal and hourly throughout the full sleep/wake cycle, among a number of other hormones.

The team found that glucose levels after meals were 17 percent higher—indicating lower glucose tolerance—in the evening than in the morning, independent of when a participant had slept or had their meals. They also found that simulating night work—by having participants sleep during the day and eat breakfast at 8 p.m.—lowered glucose tolerance over the course of multiple days. This phenomenon, known as “circadian misalignment,” may have important implications for shift workers.

Researchers hypothesize that conflicting signals from the body’s central internal clock and the behavioral cycle to various organs, such as the liver and pancreas, may contribute to these effects of misalignment on glucose control.

The new work may help the team and others develop and improve strategies for controlling glucose levels in day-active people and night workers. In addition to considering the roles of diet and exercise, some groups are pursuing drugs that may help regulate blood sugar levels in shift workers. Scheer, Morris and their colleagues are focusing on the role of meal timing.

“Because night work will never disappear, we’re investigating whether it’s possible to schedule food intake to occur at more advantageous times,” said Scheer, who is also the director of the Medical Chronobiology Program at BWH. “By better understanding the key factors that contribute to changes in glucose tolerance, we may be able to find better strategies to help mitigate the risk of diabetes for shift workers.”

Other authors of the publication are the Division of Sleep and Circadian Disorders’ Wei Wang, PhD, Orfeu Buxton, PhD, and Steven Shea, PhD, as well as former BWHers Jessica Yang, Joanna Garcia, Samantha Myers and Isadora Bozzi.