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Decreased melatonin secretion increased risk for type 2 diabetes
Researchers at Brigham and Women’s Hospital report that decreased melatonin secretion is independently associated with an increased risk for developing type 2 diabetes, according to data. However, further research is warranted to confirm these findings, researchers said.
In a case-control study nested within the Nurses’ Health Study cohort, researcher Ciaran J. McMullan, MD, of Brigham and Women’s Hospital in Boston, and colleagues identified 370 women who developed type 2 diabetes from 2000 to 2012 and matched them with controls.
According to data, the median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg among patients who developed diabetes (range: 5% to 95%; 5.5 ng/mg to 84.2 ng/mg) and 36.3 ng/mg among controls (range: 5% to 95%; 6.9 ng/mg to 110.8 ng/mg).
The researchers wrote that women with lower ratios of 6-sulfatoxymelatonin to creatinine had an increased risk for diabetes (multivariable OR=1.48; 95% CI, 1.11-1.98) per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine. Patients in the lowest category had a greater risk for developing type 2 diabetes (multivariable OR=2.17; 95% CI, 1.18-3.98) compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, they added.
Further data indicate women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases per 1,000 person-years compared with 9.27 cases per 1,000 person-years in the lowest category, they wrote.
Compared with controls, McMullan and colleagues reported patients who developed type 2 diabetes displayed significantly higher BMI; were less physically active; consumed less alcohol and cereal fiber; consumed more trans fat; and had lower overall diet quality scores. Additionally, these patients slept less per night and were more likely to use beta-blockers and have a personal history of hypertension or a family history of diabetes. Finally, biomarkers of inflammation (high-sensitivity C-reactive protein and interleukin 6) and endothelial dysfunction (intercellular adhesion molecule 1 and E-selectin) were greater among patients who developed type 2 diabetes compared with controls, they wrote.
“Further studies are needed to determine whether increasing melatonin levels (endogenously via prolonged nighttime dark exposure or exogenously via supplementation) can increase insulin sensitivity and decrease the incidence of type 2 diabetes,” McMullan and colleagues concluded.
Disclosure: This study was supported by NIH grants DK58845 and HL103607. Study researcher Hu reports consultancy services for Novo Nordisk and receiving grants from Merck and the Walnut Commission. All other researchers report no relevant financial disclosures.
Perspective
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Melatonin release from the pineal gland is regulated by light exposure and the Circadian rhythm. Peak melatonin levels occur 3 to 5 hours after the onset of sleep so that any sleep disturbance such as sleep apnea will lower melatonin levels.
Melatonin receptors are ubiquitous and are present on the pancreatic islets. Animals with receptor defects are more likely to develop diabetes; in vitro exposure to melatonin improves insulin sensitivity.
In this nested case-control study, an independent association of diabetes with lower melatonin levels was found. Even though the study was controlled for hours of sleep and the presence of snoring, there is still the possibility that disturbed sleep independently led to both insulin resistance and low melatonin levels.
Therefore, this study only proves an association and not causation. To prove that melatonin improves insulin resistance, prospective, blinded and randomized insulin clamp studies should be preformed.