The use of melatonin as sleep medication has exploded in recent years. Melatonin, a naturally occurring sleep hormone, is approved as a sleep aid for people over the age of 55, for the treatment of jetlag, and for children and young people with ADHD and other neurological disorders. The steep rise in consumption also indicates, however, that the drug is being used by other groups, including patients with type 2 diabetes. Yet several studies have suggested that glucose metabolism may be negatively affected by melatonin, necessitating more thorough investigations before it can be settled, whether it is safe to treat people with type 2 diabetes with melatonin.

This investigation has been taken on by Ulla Kampmann, who is a consultant physician at the Steno Diabetes Center Aarhus (SDCA), an associate professor at Aarhus University’s Department of Clinical Medicine and a former Danish Diabetes Academy postdoc, working in collaboration with colleagues, including SDCA staff specialist, MD, PhD Julie Støy and PhD student Esben Stistrup Lauritzen.

Ulla Kampmann, together with colleagues including SDCA staff specialist Julie Støy and PhD student Esben Stistrup Lauritzen, is responsible for the new research results.

The group has previously shown that melatonin reduces insulin sensitivity by 10% in healthy young men, who received 40 mg of melatonin during a study day. This was demonstrated in a double-blinded, randomised, placebo-controlled crossover study (Kampmann et al. Journal of Pineal Research 2021). The next step to pursue the effects of melatonin on glucose metabolism involved studying the impact of high-dose melatonin on the incretin effect, i.e. the insulin secretion observed after oral glucose intake, mediated by the gut hormones (incretin hormones) GLP-1 and GIP. As this effect is significantly reduced in patients with type 2 diabetes, it is relevant to investigate whether melatonin could be affecting insulin secretion via the incretin effect. In the study, recently published in the Journal of Clinical Endocrinology and Metabolism, Ulla Kampmann and her colleagues, working in collaboration with researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, performed an oral glucose tolerance test (OGTT) in 15 healthy young men , combined with an isoglycemic intravenous glucose infusion (IIGI) and measured changes in the blood concentrations of GLP-1 and GIP. The study participants were examined 4 times each, receiving a total of 40 mg of melatonin per day on 2 of the study days, and being given placebo on the remaining 2 days. Insulin secretion was also studied in the trial, which was randomised and double blinded.

The body produces melatonin during the night, but the doses used as a sleeping aid increase blood concentrations  up to 100 times higher compared to the natural concentration. The amount of melatonin that is produced naturally may therefore not have an effect on glucose metabolism, but in supraphysiologic effects there could possibly be a negative effect.

The human study was followed up by an animal study looking at the direct effect of melatonin on incretin hormones in rat intestines.

The human study showed that high doses of melatonin reduced the level of GIP in the gut by 20%, but the reduction in GIP levels did not have an effect on neither insulin secretion nor blood glucose.  The rat study supported the findings of the human study, as melatonin proved to reduce both GLP-1 and GIP significantly.

‘Although the results in humans are not as clear as in rats, our overall findings indicate that melatonin can affect the gut hormones GLP-1 and GIP, and thereby affect glucose metabolism’, says Ulla Kampmann. ‘As the incretin response is reduced in patients with type 2 diabetes, it is concerning if melatonin further reduces the concentration of incretin hormones. This has however not been investigated yet, but it would be very interesting to look at in a future study’, she adds.

To find out whether melatonin is beneficial or detrimental to glucose metabolism in patients with type 2 diabetes, Ulla Kampmann and her colleagues have just completed a double-blinded, randomised, placebo-controlled clinical trial looking at the effect of taking 10 mg of melatonin before bedtime every day for 3 months in patients with type 2 diabetes. The aim was to study the effects of long-term melatonin treatment on insulin sensitivity, insulin secretion, blood pressure, substrate metabolism and body composition. The results have been finalised, and the article will be published in the near future.

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READ THE ARTICLE HERE:
https://academic.oup.com/jcem/article-abstract/106/12/e5109/6321979?redirectedFrom=fulltext
2021 July 15 | doi: 10.1210/clinem/dgab521

CONTACT:
Ulla Kampmann Opstrup
Consultant physician at Steno Diabetes Center Aarhus (SDCA), Associate Professor at the Department of Clinical Medicine, Aarhus University and former postdoc with the Danish Diabetes Academy
Department of Clinical Medicine - SDCA - Steno Diabetes Center Aarhus
ulla.kampmann@clin.au.dk