"This case-control study is the first prospective evaluation of the link between melatonin secretion and type 2 diabetes and demonstrates an independent association between the 2," lead author Ciaran J. McMullan, MD, from Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News. He and his colleagues report their findings in the April 3 issue of the Journal of the American Medical Association.
"What's fascinating is that cases of diabetes had lower levels of melatonin secretion than controls," Dr. McMullan noted, "and when we compared the lowest category of melatonin secretion with the highest, they had double the risk of diabetes, even after adjustment for many potential confounding factors.
"We've shown that [melatonin] is a risk factor, but we are really interested to see whether it is a modifiable risk factor," he added, noting that the clinical relevance of these findings is currently "unclear; this won't change clinical practice, but it causes us to ask 2 important questions."
First, it should stimulate more research into what can influence melatonin secretion, he said, and second, "if we were to change an individual's melatonin secretion or melatonin levels, do we then change their risk of developing type 2 diabetes?"
Dr. McMullan said the next logical step would be to conduct further studies to see whether increasing melatonin levels — either endogenously via prolonged nighttime dark exposure or exogenously via supplementation — can increase insulin sensitivity and decrease the incidence of type 2 diabetes.
Melatonin levels lower in diabetes cases than controls
Dr. McMullan and colleagues explain that the pineal gland secretes melatonin in response to light exposure, following a diurnal pattern, with levels typically peaking 3 to 5 hours after sleep onset when it is dark. During daylight hours, there is almost no production of melatonin.
Melatonin receptors have been found throughout the body, including in pancreatic islet cells, and several lines of evidence — including animal work and human genomewide-association studies — suggest that the hormone may play a role in glucose metabolism. There have also been a number of cross-sectional studies in humans suggesting a protective effect of melatonin regarding diabetes development, but these have been small "and difficult to interpret," said Dr. McMullan.
In their prospective study, the researchers assessed participants in the Nurses' Health Study who, at baseline in 2000, did not have diabetes and who had provided blood and urine samples. They then identified 370 women who developed type 2 diabetes (self-reported) from 2000 to 2012 and matched them with 370 controls.
Associations between melatonin secretion at baseline — determined from morning urine samples — and incidence of type 2 diabetes were evaluated after researchers controlled for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction.
The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg among cases of diabetes and 36.3 ng/mg among controls.
Compared with women in the highest category of 6-sulfatoxymelatonin/creatinine ratio, those in the lowest category had an odds ratio of 2.17 of developing type 2 diabetes.
In absolute terms, the estimated diabetes incidence rate was 9.27 cases/1000 person-years among those in the lowest category of melatonin secretion compared with 4.27 cases/1000 person-years among women in the highest category.
Sleep disruption did not affect association
Dr. McMullan and colleagues note that sleep disruption has also previously been associated with type 2 diabetes. In one study, men who slept less than 5 hours per night were twice as likely to develop diabetes as those who reported sleeping 7 hours a night. Similarly, women who reported snoring on a regular basis were 2.2 times more likely to develop diabetes than women who never snored, even after adjustment for adiposity.
"Consistent with these prior studies, both short sleep duration and snoring frequency were associated with incident type 2 diabetes in our case-control study. Because sleep disruption is also associated with decreased melatonin secretion, it is possible that sleep disruption could confound the association between melatonin and diabetes," they observe.
However, adjustment for sleep duration and snoring frequency in the multivariate analysis "did not significantly alter the association of melatonin secretion with incident type 2 diabetes," they note.
Also, the nurses included in this study were, on average, around 65 years of age, so few of them were still working shifts (only around 4%), Dr. McMullan pointed out.
Source: http://www.medscape.com/viewarticle/781819
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