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Diet and lifestyle

Natural sleep hormone increases the risk of diabetes

Melatonin has been called the “hormone of darkness” and adjusts people’s internal clock. Many people with sleep problems take this wonder hormone to improve their sleep–wake cycle. New research, however, suggests that this entails risk. Melatonin also affects the regulation of blood glucose and increases the risk of type 2 diabetes. One third of the population carries a genetic variant that appears to make them more sensitive to melatonin and should therefore take precautions, such as avoiding shift work.

Just because something is natural does not mean that it is necessarily healthy. Although the human body naturally produces the hormone melatonin and taking extra melatonin helps many people to sleep better, it may also have drawbacks. Melatonin inhibits the secretion of insulin. New research shows that about every third person is more sensitive to melatonin, and they are at higher risk of developing diabetes.

“The people with this specific genetic risk variant have significantly more receptors for melatonin. This means that they are exposing themselves to increased risk if they take melatonin to improve their sleep-wake cycle or increase their melatonin level in other ways, such as by excessive night work,” says Hindrik Mulder, Principal Investigator, Molecular Metabolism, Department of Clinical Sciences Malmö, Lund University.

A specific genetic variant

Melatonin is a hormone naturally produced by the body that influences the sleep-wake cycle through effects on the circadian rhythm in humans, animals and plants. The pineal gland in the brain secretes melatonin during the dark part of the day, thereby influencing the circadian rhythm. The secretion of melatonin increases as light intensity decreases, and this naturally make people feel more sleepy when it becomes dark. Melatonin is also available as pills, and most people who take these experience no immediate side-effects.

“Today, we know for certain that melatonin directly influences the secretion of other substances. When melatonin binds to its natural receptor, it suppresses the production of cyclic adenosine monophosphate (cAMP), a signalling molecule. The reduced cAMP signals make the cells in the islets of Langerhans reduce the release of insulin, and this disturbs the regulation of blood glucose.”

Melatonin thus influences the normal regulation of blood glucose, and permanent disturbances in the secretion of melatonin can therefore also have lasting effects on the regulation of blood glucose and thus on the development of diabetes. One in three people has a specific genetic variant, increasing melatonin signalling, which means that these changes may have an even stronger effect.

“People with a specific genetic variant of melatonin receptor 1B produce substantially more of this receptor. These people secrete less insulin since melatonin inhibits insulin secretion, and we think that this is why they more often develop diabetes.”

Natural substances can be harmful

The problem of long-term imbalance in the regulation of blood glucose may be further exacerbated if people with this genetic variant take melatonin to regulate their sleep–wake cycle. Because many people with diabetes have sleep problems, this is a vicious circle.

“Too much melatonin reduces the secretion of insulin and increases the risk of diabetes. Insomnia and working nights influence everyone’s secretion of melatonin and thereby insulin. People carrying this genetic variant should therefore perhaps be more careful and should ideally not work nights or avoid melatonin, at least as a regular medicine.”

Although this new research indicates the potential harm of melatonin, Hindrik Mulder also warns against becoming excessively cautious about taking it. Researchers have actually only scratched the surface of understanding the relationship between sleep, melatonin and diabetes.

“The effect is just not that strong. The people with this genetic variant only have a 10% increase in risk. The most important thing to remember is that natural substances can be just as dangerous as or even more dangerous than chemically produced substances. For example, insulin can be fatal at an inappropriate dose. Similarly, excessive consumption of melatonin may have unwanted side-effects.”

Melatonin signalling and type 2 diabetes risk: too little, too much or just right?” has been published in Diabetologia. In 2016 and 2017, the Novo Nordisk Foundation awarded grants to Hindrik Mulder for the project Elucidating the Diabetogenic Mechanisms of Melatonin Signalling Using Induced Pluripotent Stem Cells and Genome Editing.

Hindrik Mulder
Principal Investigator
My scientific work has focused on the insulin-secreting beta-cells in the islets of Langerhans. They release the hormone insulin, which controls whole body metabolism. Insufficient secretion of insulin is a requirement for the development of Type 2 Diabetes, a disease with a currently soaring incidence. In recent years, my research activities have been devoted to metabolism in islets but I started out with examining islet hormones other than insulin.