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The Risk of Developing T2DM Increases with Melatonin at Mealtimes

People with the genetic variant MTNR1B may be at a greater risk.

There is no evidence of experimental studies performed to test the effect of the MTNR1B gene variant on glucose metabolism in humans during exposure to melatonin. Therefore, researchers wanted to investigate whether this gene variant influenced the effect of melatonin 5mg on glucose tolerance assessed by OGTT 75g at different times of the day (morning and evening) compared to a placebo.

Researcher Frank Scheer, PhD, associate professor of medicine at Harvard Medical School and director of the medical chronobiology at Brigham and Women’s Hospital, and colleagues assessed 17 normoglycemic women for the study. From the group of participants, 11 of them were carriers of the gene variant MTNR1B. All participants received melatonin or placebo in the morning and evening, followed by an OGTT. Blood samples were taken before and at 30-minute intervals after taking glucose doses for the following 2 hours.

Investigators found the effect of melatonin on glucose area under the curve (AUC) to be different between carriers and non-carriers in the morning (P = 0.036). In the carrier group, glucose tolerance was 6-fold worse than compared to the non-carrier group. Furthermore, there was a difference noted with the effect of melatonin on glucose concentration 2 hours post OGTT between carriers and non-carriers (P = 0.04) and after adjustment for age and BMI (P = 0.017). The effect of melatonin on glucose AUC and insulin measures in the evening did not have any significant differences between carriers and non-carriers.

Authors believe this the first study to show that a person’s genetic profile may affect their ability to tolerate glucose when they take melatonin. Furthermore, when people take melatonin, the genetic risk variant in MTNR1B causes a much greater change in glucose tolerance in carriers vs. non-carriers. This was observed to be the fact even in people who are not obese and not diabetic. Authors also believe that it may be important to take genetics into account when considering food consumption and melatonin with respect to time of administration.

Practice Pearls:

  • The genetic risk variant MTNR1B rs10830963 worsens the effect of melatonin on glucose tolerance.
  • The importance of genotyping should be emphasized in order to make personalized recommendations, especially in individuals consuming food around the time melatonin levels are elevated.
  • Future studies are warranted in vulnerable populations to further evaluate results of this study into real-world, clinically relevant recommendations.

Garaulet, Marta, et al. “Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans.” Metabolism (2015).