Possible Link Found Between Diabetes and Human Circadian Rhythms

A new gene variant has been discovered that raises blood glucose levels through melatonin secretion. This finding possibly establishes a previously unknown link between human circadian rhythms (sleep-wake cycles, regulated by melatonin), and diabetes.

The study consisted of a meta-analyses, including data from 13 different studies and over 82,000 participants (18,000 with diabetes). The goal of the study was to search for gene variants within these individuals that have the effect of raising blood glucose levels, and increasing the risk for the development of type 2 diabetes. These discovered gene variants would also have the ability of pinpointing the mechanisms by which healthy individuals regulate blood glucose levels, by demonstrating which genes must necessarily function properly to limit diabetic risk.

A variant of the gene MTNR1B, which resides within insulin-producing cells, was identified by researchers as raising blood glucose levels and increasing diabetic risk. MTNR1B is also known to be a receptor for melatonin, and the gene variant of MTNR1B is thought to interfere with insulin production due to melatonin. Specifically, MTNR1B “encodes one of the two known melatonin receptors. It is assumed that this receptor inhibits the release of insulin via the neural hormone melatonin.”

Melatonin is thought to be the primary regulator of sleep-wake cycles in human beings. Nighttime melatonin levels are significantly higher than daytime levels, accounting for the well-established circadian rhythm present in humans. On the other hand, insulin levels are typically much lower at night than in the day.

Previously, the fact that insulin levels are low at night was thought to be unrelated to melatonin levels being high. However, armed with the new knowledge that the gene variant of MTNR1B raises blood glucose levels, researchers are speculating that a link between melatonin levels (circadian rhythms) and insulin production exists, which when irregular, can lead to diabetes. The hope is that further establishment and investigation into this connection will lead to novel treatments for diabetes, perhaps focused upon melatonin production, instead of direct insulin administration.

Source: Defeat Diabetes Foundation: Winkler, Sven. Illig, Thomas. Whichman, Erich. Nature Genetics news release. January 2009.