Exogenous
melatonin ameliorates
insulin resistance in animals, while among humans, polymorphisms in the
melatonin receptor gene are associated with
insulin resistance. We aimed to investigate the association of endogenous nocturnal
melatonin secretion with
insulin resistance in humans. We analyzed the association between endogenous nocturnal
melatonin secretion, estimated by measuring the main
melatonin metabolite,
6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence of
insulin resistance based on fasting blood samples collected in a cross-sectional study of 1,075 US women (1997-1999) without diabetes,
hypertension, or
malignancy. Urinary
6-sulfatoxymelatonin level was standardized to urinary
creatinine level;
insulin resistance was defined as an
insulin sensitivity index value (using the McAuley formula) less than 7.85. Logistic regression models included adjustment for age, body mass index, smoking, physical activity, alcohol intake, dietary glycemic index, family history of
diabetes mellitus, blood pressure, plasma total
cholesterol,
uric acid, and estimated glomerular filtration rate. Higher nocturnal
melatonin secretion was inversely associated with
insulin levels and
insulin resistance. In fully adjusted models, the odds ratio for
insulin resistance was 0.45 (95% confidence interval: 0.28, 0.74) among women in the highest quartile of urinary 6-sulfatoxymelatonin:
creatinine ratio compared with women in the lowest quartile. Nocturnal
melatonin secretion is independently and inversely associated with
insulin resistance.