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Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology

Lane, J.M. and Chang, A.-M. and Bjonnes, A.C. and Aeschbach, D. and Anderson, C. and Cade, B.E. and Cain, S.W. and Czeisler, C.A. and Gharib, S.A. and Gooley, J.J. and Gottlieb, D.J. and Grant, S.F.A. and Klerman, E.B. and Lauderdale, D.S. and Lockley, S.W. and Munch, M. and Patel, S. and Punjabi, N.M. and Rajaratnam, S.M.W. and Rueger, M. and Hilaire, M.A.St. and Santhi, N. and Scheuermaier, K. and Van Reen, E. and Zee, P.C. and Shea, S.A. and Duffy, J.F. and Buxton, O.M. and Redline, S. and 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), pp. 1741-1751. American Diabetes Association. DOI: 10.2337/db15-0999 ISSN 0012-1797

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Abstract

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.

Item URL in elib:https://elib.dlr.de/108373/
Document Type:Article
Title:Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Lane, J.M.UNSPECIFIEDUNSPECIFIED
Chang, A.-M.UNSPECIFIEDUNSPECIFIED
Bjonnes, A.C.UNSPECIFIEDUNSPECIFIED
Aeschbach, D.daniel.aeschbach (at) dlr.deUNSPECIFIED
Anderson, C.UNSPECIFIEDUNSPECIFIED
Cade, B.E.UNSPECIFIEDUNSPECIFIED
Cain, S.W.UNSPECIFIEDUNSPECIFIED
Czeisler, C.A.UNSPECIFIEDUNSPECIFIED
Gharib, S.A.UNSPECIFIEDUNSPECIFIED
Gooley, J.J.UNSPECIFIEDUNSPECIFIED
Gottlieb, D.J.UNSPECIFIEDUNSPECIFIED
Grant, S.F.A.UNSPECIFIEDUNSPECIFIED
Klerman, E.B.UNSPECIFIEDUNSPECIFIED
Lauderdale, D.S.UNSPECIFIEDUNSPECIFIED
Lockley, S.W.UNSPECIFIEDUNSPECIFIED
Munch, M.UNSPECIFIEDUNSPECIFIED
Patel, S.UNSPECIFIEDUNSPECIFIED
Punjabi, N.M.UNSPECIFIEDUNSPECIFIED
Rajaratnam, S.M.W.UNSPECIFIEDUNSPECIFIED
Rueger, M.UNSPECIFIEDUNSPECIFIED
Hilaire, M.A.St.UNSPECIFIEDUNSPECIFIED
Santhi, N.UNSPECIFIEDUNSPECIFIED
Scheuermaier, K.UNSPECIFIEDUNSPECIFIED
Van Reen, E.UNSPECIFIEDUNSPECIFIED
Zee, P.C.UNSPECIFIEDUNSPECIFIED
Shea, S.A.UNSPECIFIEDUNSPECIFIED
Duffy, J.F.UNSPECIFIEDUNSPECIFIED
Buxton, O.M.UNSPECIFIEDUNSPECIFIED
Redline, S.UNSPECIFIEDUNSPECIFIED
Scheer, F.A.J.L.UNSPECIFIEDUNSPECIFIED
Saxena, R.UNSPECIFIEDUNSPECIFIED
Date:2016
Journal or Publication Title:Diabetes
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
DOI :10.2337/db15-0999
Page Range:pp. 1741-1751
Publisher:American Diabetes Association
ISSN:0012-1797
Status:Published
Keywords:Sleep, Circadian System, Melatonin, Diabetes Risk, MTNR1B Gene
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Aeronautics
HGF - Program Themes:air traffic management and operations
DLR - Research area:Aeronautics
DLR - Program:L AO - Air Traffic Management and Operation
DLR - Research theme (Project):L - Human factors and safety in Aeronautics
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Flight Physiology
Deposited By: Sender, Alina
Deposited On:29 Nov 2016 09:45
Last Modified:31 Jul 2019 20:05

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