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Melatonin Seen to Raise Risk of Type 2 Diabetes in People with a Common Gene Variant

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Melatonin Seen to Raise Risk of Type 2 Diabetes in People with a Common Gene Variant
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Melatonin, known as the sleep hormone, impairs insulin secretion in people with a common gene variant, according to researchers with Lund University in Sweden. The study, “A Common Variant in TFB1M Is Associated with Reduced Insulin Secretion and Increased Future Risk of Type 2 Diabetes, was published in the journal Cell Metabolism.

“This could explain why the risk of type 2 diabetes is greater among, for instance, overnight workers or people with sleeping disorders,” Professor Hindrik Mulder, one of the study’s lead authors, said in a news release.

Melatonin is a hormone that anticipates the daily onset of nighttime darkness, and is involved in the entrainment (synchronization) of the circadian rhythms of physiological functions, including sleep timing, blood pressure regulation, and seasonal reproduction.

Type 2 diabetes is a multifactorial and polygenic disorder, characterized by impaired insulin secretion from pancreatic β cells, and insulin resistance in peripheral tissues. Insulin secretion is controlled by fuel metabolism in pancreatic β cells.

The research team had previously conducted a large gene mapping study, in which it found that the gene variant of the melatonin receptor 1B increases a person’s risk of developing type 2 diabetes. The variant leads to an increase in the level of the 1B receptor on the surface of insulin cells, making the cells more sensitive to melatonin by impairing their ability to secrete insulin.

“A third of all people carry this specific gene variant. Our results show that the effect of melatonin is stronger in them. We believe that this explains their increased risk of developing type 2 diabetes,” Professor Mulder said.

In this study, the team used mice and human β cells to understand the underlying processes, and also to investigate how the effects of drugs are influenced by genetic factors. The researchers recruited 23 healthy individuals and carriers of the gene variant, and 22 non-carriers; all had similar family histories of diabetes. Participants received four milligrams of melatonin at bedtime for a period of three months.

Results showed that, after the three months of melatonin treatment, the blood concentration of glucose (sugar) was higher in all participants, but more evident in those with the risk gene, who were unable to increase insulin secretion. In fact, compared to the control group, those who carried the risk gene had significantly lower levels of insulin secretion.

Evidence has shown that overnight shift workers are more prone to develop metabolic conditions such as type 2 diabetes. “It is perhaps therefore less suitable for carriers of the risk gene to work overnight shifts, as the level of melatonin will probably increase at the same time as the effects of the increase are enhanced. There is still no scientific support for this theory, but it ought to be studied in the future, on the basis of our new findings,” Professor Mulder concluded.

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