Nocturnal melatonin secretion and risk of type 2 diabetes: a prospective cohort study

Context Melatonin regulates circadian rhythms and influences glucose metabolism. Altered melatonin secretion may contribute to the pathogenesis of type 2 diabetes (T2D), but prospective population-based evidence is scarce. Objective To examine whether low nocturnal melatonin secretion is associated with an increased risk of incident T2D in adults. Design Prospective cohort study with follow-up from 2013 to 2023 (median 6.5 years). Setting The Malmö Offspring Study, a population-based cohort in southern Sweden. Participants A total of 4491 adults (52% women, aged 18-75 years) without T2D and melatonin supplementation at baseline were included. Main Outcome Measure(s) Incident T2D identified via national and regional health registers. Nocturnal melatonin secretion was assessed as the urinary 6-sulfatoxymelatonin-to-creatinine ratio (aMT6s/Cr) from first-morning urine samples, categorized into sex-specific quintiles. Results During follow-up, 171 participants developed T2D. Participants in the lowest quintile of aMT6s/Cr had a higher T2D risk than those in quintiles 2-5 (multivariable adjusted hazard ratio [HR] 1.51, 95% CI 1.09–2.09). The association remained significant after additional adjustment for sleep duration and disruption (HR 1.54, 95% CI 1.11–2.13). When analyzing T2D development per 1-SD higher sex-standardized log aMT6s/Cr, HR was 0.84 (95% CI 0.73–0.97). Associations were consistent across sex, age, and BMI subgroups. Conclusions Low nocturnal melatonin secretion was independently associated with a higher incidence of T2D in adults. A key limitation is the reliance on a single morning urine sample to estimate melatonin secretion. The findings support circadian regulation as a determinant of metabolic health and warrant further investigation of melatonin pathways in diabetes prevention.