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

Sojakka Smith, Einar LU orcid ; Franzén, Anna LU orcid ; Pihlsgård, Mats LU ; Nilsson, Peter M LU ; Timpka, Simon LU orcid and Enhörning, Sofia LU (2026) In The Journal of clinical endocrinology and metabolism 111(6). p.1705-1712
Abstract

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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
The Journal of clinical endocrinology and metabolism
volume
111
issue
6
pages
1705 - 1712
publisher
Oxford University Press
external identifiers
  • pmid:41389002
  • scopus:105038841282
ISSN
1945-7197
DOI
10.1210/clinem/dgaf667
language
English
LU publication?
yes
additional info
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.
id
313ddaf6-f6b5-446e-a3c1-3cb19121555d
date added to LUP
2026-05-29 14:57:10
date last changed
2026-06-02 03:12:48
@article{313ddaf6-f6b5-446e-a3c1-3cb19121555d,
  abstract     = {{<p>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.</p><p>OBJECTIVE: To examine whether low nocturnal melatonin secretion is associated with an increased risk of incident T2D in adults.</p><p>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.</p><p>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.</p><p>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.</p>}},
  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}},
}