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Studies on melatonin might help explain why some shift workers tend to face a higher risk of diabetes than the general population.

Fred Lum/The Globe and Mail

Could low levels of melatonin be a harbinger of diabetes?

Melatonin is a hormone that's best known for regulating the body's internal 24-hour clock – or circadian rhythm. It is produced by the brain, mainly at night, as we sleep.

In a new study, published Tuesday in the Journal of the American Medical Association, U.S. researchers found an association between low levels of melatonin and an increased risk of developing type 2 diabetes.

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The findings are based on women who are enrolled in the Nurses' Health Study, a large, ongoing project to identify factors that influence overall health.

From this group, the researchers identified a subgroup of 370 participants who developed diabetes between 2000 and 2012. They also selected 370 non-diabetic women of the same age and race to serve as a control group. The researchers then used urine samples, collected before anyone had developed diabetes, to determine their nighttime secretion of melatonin.

The study participants with lowest melatonin levels faced two times the risk of developing diabetes, compared with those with the highest levels, said the lead researcher, Dr. Ciaran McMullan of Brigham and Women's Hospital in Boston.

If the results are confirmed by follow-up studies, it could open up a new way of preventing diabetes by boosting melatonin levels – either by getting more sleep or popping melatonin supplements.

Earlier work provides some reassurance the researchers are on the right track.

Some years ago, scientists discovered that there are melatonin receptors throughout the body, including in the pancreas, which produces insulin, the hormone that helps move glucose from the bloodstream into the tissues of the body where it is used for energy.

Patients with type 2 diabetes don't make enough insulin, or their cells don't respond properly to what they do produce.

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Recent genetic research has revealed that people who are born with genetic mutations in the melatonin receptors of the pancreas face an elevated risk of getting diabetes.

"It was a little bit of a surprise when the mutations were first identified," said McMullan, noting they were found in Caucasian, Asian and African-American populations. "These genetic studies implicate melatonin in the development of diabetes," he added.

Other research has also linked diabetes and sleep, which in turn, implicates melatonin. (Melatonin production typically peaks between three to five hours after the onset of sleep, with almost no secretions occurring during daylight.)

One study showed that people who sleep less that six hours a night have an increased risk of diabetes, compared with those who sleep seven to eight hours. The same study found that people who sleep more than nine hours are also at an increased risk of diabetes. "So you could say there is a sweet spot for how much we sleep and the risk of diabetes," noted McMullan.

In another study, researchers disrupted the sleep of healthy individuals, either by making them sleep less than normal or altering the time of day they were allowed to get shut-eye.

"What the researchers found is that they could induce almost a pre-diabetic state in these individuals, just by disrupting their sleep. And when you return them to their normal sleep, they return to a normal glucose metabolism."

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These studies might help explain why some shift workers tend to face a higher risk of diabetes than the general population.

But possibly the most promising research has come from laboratory work conducted on animals. In particular, scientists have found that feeding diabetic-prone rats a melatonin-enriched diet can reduce their odds of getting the disease.

However, McMullan is extremely reluctant to draw conclusions about what might work in humans, based on research carried out in animals.

"Further research needs to be done to look at what causes the differences in melatonin secretion in individuals. And we need to see if we can change the risk of developing type 2 diabetes by altering melatonin levels."

Although a lot more needs to be done, if the work pays off, it could lead to big changes in medicine. "Diabetes is such a huge problem that we should try to find every way we can to prevent it," said McMullan.

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