Will We be Giving Melatonin to Prevent and Treat Type 2 Diabetes?
Abstract & Commentary
By Joseph E. Scherger, MD, MPH
Vice President, Primary Care, Eisenhower Medical Center; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles
Dr. Scherger reports no financial relationships relevant to this field of study.
Synopsis: A case-control study of women in the Nurses’ Health Study Cohort showed that lower melatonin secretion is independently associated with a higher risk of developing type 2 diabetes. There is a physiologic basis for this finding since melatonin has a role in glucose metabolism and lack of melatonin is associated with increased insulin resistance.
Source: McMullan CJ, et al. Melatonin secretion and the incidence of type 2 diabetes. JAMA 2013;309:1388-1396.
A study group at harvard used the nurses’ health Study Cohort and identified 370 women who developed type 2 diabetes between 2000 and 2012, and matched them with 370 controls. These women provided first morning blood and urine samples between 1999 and 2000 so metabolites of melatonin could be measured. It was found that women in the lowest category of melatonin secretion had more than twice the likelihood of developing diabetes (9.27 cases/1000 person-years) compared with those in the highest category of melatonin secretion (4.27 cases/1000 person-years).
Melatonin is secreted by the pineal gland in the brain and is controlled by the "biologic clock" in the hypothalamus that is regulated by light exposure. The secretion of melatonin follows a diurnal pattern and peaks about 3-5 hours after sleep onset and in darkness. A deficiency of melatonin, common in the elderly, is a cause of much insomnia, particularly early awakening.1
The role of melatonin in glucose metabolism is less well known, but has been studied extensively.2 Melatonin receptors are found throughout the body, including the islet cells of the pancreas. Melatonin is felt to play an important role in energy metabolism and the regulation of body weight.2
Giving melatonin had a protective effect against the onset of diabetes in rats prone to diabetes, and improvements were also seen in the animals’ cholesterol and triglyceride levels.3,4 Studies in humans have been done —but are small in scale — and do show a protective effect of melatonin in diabetes development.5
Short sleep duration and snoring frequency are associated with decreased melatonin secretion and type 2 diabetes development. The authors postulate there is a causal role for reduced melatonin secretion and diabetes risk with a call for larger studies.
Physicians trained in the 1970s before CT scans and MRIs relied on a calcified pineal gland to look for a shift in the brain with head trauma and stroke. Elderly pineal glands calcify and are less likely to secrete melatonin over time. This explains in part the declining hours of sleep as we age. I regularly give melatonin to patients who have short sleep duration insomnia and use it myself when I know my regular sleep will be disrupted such as with long-distance travel.
The fact that people who sleep less gain more weight does not simply reflect that they eat more. Something else seems to be going on and the melatonin hypothesis may help explain that. If melatonin plays a role in the development of type 2 diabetes, that is a huge breakthrough. Think of it, an inexpensive over-the-counter medication is available to both prevent and treat type 2 diabetes!
I hope randomized, controlled trials will be done with melatonin for the prevention and treatment of type 2 diabetes. I am not ready to give it to all my prediabetic and diabetic patients, but for those with sleep problems, I do give it and will begin watching their blood sugars and HbA1c. This could be a very exciting development.
1. Claustrat B, et al. The basic physiology and pathophysiology of melatonin. Sleep Med Rev 2005;9:11-24.
2. Peschke E, Muhlbauer E. New evidence for a role of melatonin in glucose metabolism. Best Pract Res Clin Endocrinol Metab 2010;24:829-841.
3. Prunet-Marcassus B, et al. Melatonin reduces body weight in Sprague Dawley rats with diet-induced obesity. Endocrinology 2003;144:5347-5352.
4. Sartori C, et al. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology 2009;150:5311-5317.
5. Peschke E, et al. Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurinal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res 2006;40: