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Diabetes DOI:10.2337/db15-0999

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

Publication TypeJournal Article
Year of Publication2016
AuthorsLane, JM, Chang, A-M, Bjonnes, AC, Aeschbach, D, Anderson, C, Cade, BE, Cain, SW, Czeisler, CA, Gharib, SA, Gooley, JJ, Gottlieb, DJ, Grant, SFA, Klerman, EB, Lauderdale, DS, Lockley, SW, Munch, M, Patel, S, Punjabi, NM, Rajaratnam, SMW, Rueger, M, St Hilaire, MA, Santhi, N, Scheuermaier, K, Van Reen, E, Zee, PC, Shea, SA, Duffy, JF, Buxton, OM, Redline, S, Scheer, FAJL, Saxena, R
JournalDiabetes
Volume65
Issue6
Pages1741-51
Date Published2016 Jun
ISSN1939-327X
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 in-laboratory 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.

URLhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26868293
DOI10.2337/db15-0999
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26868293?dopt=Abstract

Alternate JournalDiabetes
PubMed ID26868293
PubMed Central IDPMC4878414
Grant ListR21 AT002571 / AT / NCCIH NIH HHS / United States
K01 HL115458 / HL / NHLBI NIH HHS / United States
R01 DK099512 / DK / NIDDK NIH HHS / United States
U01 HL053916 / HL / NHLBI NIH HHS / United States
R01 HL118601 / HL / NHLBI NIH HHS / United States
U01 HL063463 / HL / NHLBI NIH HHS / United States
K24 HL105664 / HL / NHLBI NIH HHS / United States
R01 HL094654 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
T32 HL007901 / HL / NHLBI NIH HHS / United States
RC2 HL101340 / HL / NHLBI NIH HHS / United States
R01 HL080978 / HL / NHLBI NIH HHS / United States
R01 AG006072 / AG / NIA NIH HHS / United States
M01 RR002635 / RR / NCRR NIH HHS / United States
R01 HL098433 / HL / NHLBI NIH HHS / United States
R01 HL077399 / HL / NHLBI NIH HHS / United States
R01 HL077453 / HL / NHLBI NIH HHS / United States
U01 HL053941 / HL / NHLBI NIH HHS / United States
R01 MH045130 / MH / NIMH NIH HHS / United States
R01 HL114088 / HL / NHLBI NIH HHS / United States
P01 AG009975 / AG / NIA NIH HHS / United States
F32 DK102323 / DK / NIDDK NIH HHS / United States
U01 HL053934 / HL / NHLBI NIH HHS / United States
U01 HL063429 / HL / NHLBI NIH HHS / United States
R21 DK089378 / DK / NIDDK NIH HHS / United States
R01 NS054277 / NS / NINDS NIH HHS / United States
R21 HL121728 / HL / NHLBI NIH HHS / United States
R01 AG044416 / AG / NIA NIH HHS / United States
R01 HL093279 / HL / NHLBI NIH HHS / United States
U01 HL053937 / HL / NHLBI NIH HHS / United States
R01 HL094806 / HL / NHLBI NIH HHS / United States