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Melatonin and mealtime: Common genetic difference could put some at greater risk of diabetes

New study explores how genetics influences the effects of taking melatonin close to mealtime

Brigham and Women's Hospital

Researchers from Brigham and Women's Hospital (BWH) and the University of Murcia, Spain, have shed new light on why people who carry a common genetic mutation may be more at risk for developing type 2 diabetes. By carefully studying healthy subjects, researchers were able to chart the effect of melatonin supplements on blood sugar control. Their results, reported in Metabolism, suggest that taking melatonin close to mealtimes may put people with a common genetic variant more at risk.

"Our work is the first to show that a person's genetic profile could impact their ability to tolerate glucose when they take melatonin," said co-corresponding author Frank Scheer, PhD, associate professor of medicine at Harvard Medical School and the Director of the Medical Chronobiology at BWH.

"Our results suggest that we may need to exert caution when taking melatonin close to meal times, especially in carriers of the risk variant," said co-corresponding author Marta Garaulet, PhD, a full professor of Physiology at the University of Murcia.

As many as 50 percent of people of European ancestry carry this genetic variation in MTNR1B, a gene that encodes a melatonin receptor. Previous studies have found that this mutation increases a person's risk of diabetes, but exactly how and why it influences blood sugar control has remained poorly understood and has mostly been studied during the daytime, when naturally occurring melatonin concentrations are very low.

Scheer, Garaulet and their colleagues studied members of a female rugby team at the University of Murcia to investigate the effects of taking melatonin supplements on blood sugar levels. By looking at a small group of similar subjects, the research team could narrow in on the effects of melatonin and limit other possible causes of differences in results. Each recipient received either a dose of melatonin or a placebo in the morning (9 a.m.) and evening (9 p.m.), followed by a large dose of glucose, a so called oral glucose tolerance test. Blood samples were taken before and at 30-minute intervals after they received the glucose doses for the next two hours.

Of the 17 participants, 11 were carriers of the genetic risk variant and six were not. The research team found that in the morning, the effects of melatonin on ability to control blood sugar levels differed significantly between the two groups, finding that the carriers' ability to control blood sugar levels was six times worse than non-carriers'. In the evening, no significant differences were found between the two groups. The absence of the effect in the evening may have been due to a limited sample size.

"Our data suggest that when subjects take melatonin, the genetic risk variant in MTNR1B causes a much greater change in glucose tolerance in carriers compared to non-carriers, even in people who are not obese and not diabetic," said Scheer. "Our results suggest that it may be important to take genetics into account when thinking about timing of food consumption and melatonin administration." The team notes that further, large-scale studies will be needed in vulnerable populations before clinical recommendations can be made.

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This study was supported by grants from the Spanish Government of Science and Innovation (BFU2011-24720), the Séneca Foundation from the Government of Murcia (15123/PI/10) and the NIH (R21 DK089378).

Other researchers who contributed to this study include Purificación Gómez-Abellán, Patricia Rubio-Sastre, Juan A. Madrid and Richa Saxena.

Paper cited: Garaulet M et al. "Common Type 2 diabetes-risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans." Metabolism. doi:10.1016/j.metabol.2015.08.003

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits, nearly 46,000 inpatient stays and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $600 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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