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.
METHODS: This prospective cohort study, with follow-up from 2013 to 2023 (median 6.5 years), included a total of 4491 adults (52% women, aged 18-75 years) without T2D and melatonin supplementation at baseline, from the Malmö Offspring Study, a population-based cohort in southern Sweden. Incident T2D was 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 to 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, the HR was 0.84 (95% CI 0.73-0.97). Associations were consistent across sex, age, and BMI subgroups.
CONCLUSION: 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.
}}, author = {{Sojakka Smith, Einar and Franzén, Anna and Pihlsgård, Mats and Nilsson, Peter M and Timpka, Simon and Enhörning, Sofia}}, issn = {{1945-7197}}, keywords = {{Humans; Diabetes Mellitus, Type 2/epidemiology; Melatonin/urine; Female; Middle Aged; Adult; Male; Prospective Studies; Aged; Circadian Rhythm/physiology; Adolescent; Sweden/epidemiology; Young Adult; Risk Factors; Follow-Up Studies; Incidence; Biomarkers/urine}}, language = {{eng}}, month = {{05}}, number = {{6}}, pages = {{1705--1712}}, publisher = {{Oxford University Press}}, series = {{The Journal of clinical endocrinology and metabolism}}, title = {{Nocturnal melatonin secretion and risk of type 2 diabetes : a prospective cohort study}}, url = {{http://dx.doi.org/10.1210/clinem/dgaf667}}, doi = {{10.1210/clinem/dgaf667}}, volume = {{111}}, year = {{2026}}, }