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Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology

Lane, J.M., Chang, A.-M., Bjonnes, A.C., Aeschbach, D., Anderson, C., Cade, B.E., Cain, S.W., Czeisler, C.A., Gharib, S.A., Gooley, J.J. , Gottlieb, D.J., Grant, S.F.A., Klerman, E.B., Lauderdale, D.S., Lockley, Steven, Munch, M., Patel, S., Punjabi, N.M., Rajaratnam, S.M.W., Rueger, M., St. Hilaire, M.A., Santhi, Nayantara, Scheuermaier, K., Van Reen, E., Zee, P.C., Shea, S.A., Duffy, J.F., Buxton, O.M., Redline, S., Scheer, F.A.J.L. and Saxena, R. (2016) Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology Diabetes, 65 (6). pp. 1741-1751.

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The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive inlaboratory protocols (n =58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele. © 2016 by the American Diabetes Association.

Item Type: Article
Authors :
Lane, J.M.
Chang, A.-M.
Bjonnes, A.C.
Aeschbach, D.
Anderson, C.
Cade, B.E.
Cain, S.W.
Czeisler, C.A.
Gharib, S.A.
Gooley, J.J.
Gottlieb, D.J.
Grant, S.F.A.
Klerman, E.B.
Lauderdale, D.S.
Munch, M.
Patel, S.
Punjabi, N.M.
Rajaratnam, S.M.W.
Rueger, M.
St. Hilaire, M.A.
Scheuermaier, K.
Van Reen, E.
Zee, P.C.
Shea, S.A.
Duffy, J.F.
Buxton, O.M.
Redline, S.
Scheer, F.A.J.L.
Saxena, R.
Date : 2016
DOI : 10.2337/db15-0999
Uncontrolled Keywords : insulin, melatonin, glucose blood level, melatonin, melatonin 2 receptor, MTNR1B protein, human, actimetry, adult, aged, Article, circadian rhythm, cross-sectional study, female, gene, genetic association, genetic variability, human, insulin release, male, MTNR1B gene, non insulin dependent diabetes mellitus, polysomnography, priority journal, protein secretion, protein synthesis, self report, sleep, sleep time, allele, analysis, blood, circadian rhythm, diet restriction, genetic variation, genetics, glucose blood level, non insulin dependent diabetes mellitus, pathophysiology, phenotype, risk factor, secretion (process), sleep, young adult, Adult, Alleles, Blood Glucose, Circadian Rhythm, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Fasting, Female, Genetic Variation, Humans, Male, Melatonin, Phenotype, Receptor, Melatonin, MT2, Risk Factors, Sleep, Young Adult
Depositing User : Clive Harris
Date Deposited : 17 Jun 2020 01:08
Last Modified : 17 Jun 2020 12:20

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