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

Jacqueline M. Lane, Anne Marie Chang, Andrew C. Bjonnes, Daniel Aeschbach, Clare Anderson, Brian E. Cade, Sean W. Cain, Charles A. Czeisler, Sina A. Gharib, Joshua J. Gooley, Daniel J. Gottlieb, Struan F A Grant, Elizabeth B. Klerman, Diane S. Lauderdale, Steven W. Lockley, Miriam Munch, Sanjay Patel, Naresh M. Punjabi, Shanthakumar M W Rajaratnam, Melanie RuegerMelissa A. St. Hilaire, Nayantara Santhi, Karin Scheuermaier, Eliza Van Reen, Phyllis C. Zee, Steven Shea, Jeanne F. Duffy, Orfeu M. Buxton, Susan Redline, Frank A J L Scheer, Richa Saxena

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1741-1751
Number of pages11
JournalDiabetes
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Fingerprint

Melatonin
Sleep
Alleles
Actigraphy
Type 2 Diabetes Mellitus
Polysomnography
Self Report
Blood Glucose
Fasting
Cross-Sectional Studies
Hormones
Light

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Lane, J. M., Chang, A. M., Bjonnes, A. C., Aeschbach, D., Anderson, C., Cade, B. E., ... Saxena, R. (2016). Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes, 65(6), 1741-1751. https://doi.org/10.2337/db15-0999

Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. / Lane, Jacqueline M.; Chang, Anne Marie; Bjonnes, Andrew C.; Aeschbach, Daniel; Anderson, Clare; Cade, Brian E.; Cain, Sean W.; Czeisler, Charles A.; Gharib, Sina A.; Gooley, Joshua J.; Gottlieb, Daniel J.; Grant, Struan F A; Klerman, Elizabeth B.; Lauderdale, Diane S.; Lockley, Steven W.; Munch, Miriam; Patel, Sanjay; Punjabi, Naresh M.; Rajaratnam, Shanthakumar M W; Rueger, Melanie; St. Hilaire, Melissa A.; Santhi, Nayantara; Scheuermaier, Karin; Van Reen, Eliza; Zee, Phyllis C.; Shea, Steven; Duffy, Jeanne F.; Buxton, Orfeu M.; Redline, Susan; Scheer, Frank A J L; Saxena, Richa.

In: Diabetes, Vol. 65, No. 6, 01.06.2016, p. 1741-1751.

Research output: Contribution to journalArticle

Lane, JM, Chang, AM, 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, S, Duffy, JF, Buxton, OM, Redline, S, Scheer, FAJL & Saxena, R 2016, 'Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology', Diabetes, vol. 65, no. 6, pp. 1741-1751. https://doi.org/10.2337/db15-0999
Lane JM, Chang AM, Bjonnes AC, Aeschbach D, Anderson C, Cade BE et al. Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes. 2016 Jun 1;65(6):1741-1751. https://doi.org/10.2337/db15-0999
Lane, Jacqueline M. ; Chang, Anne Marie ; Bjonnes, Andrew C. ; Aeschbach, Daniel ; Anderson, Clare ; Cade, Brian E. ; Cain, Sean W. ; Czeisler, Charles A. ; Gharib, Sina A. ; Gooley, Joshua J. ; Gottlieb, Daniel J. ; Grant, Struan F A ; Klerman, Elizabeth B. ; Lauderdale, Diane S. ; Lockley, Steven W. ; Munch, Miriam ; Patel, Sanjay ; Punjabi, Naresh M. ; Rajaratnam, Shanthakumar M W ; Rueger, Melanie ; St. Hilaire, Melissa A. ; Santhi, Nayantara ; Scheuermaier, Karin ; Van Reen, Eliza ; Zee, Phyllis C. ; Shea, Steven ; Duffy, Jeanne F. ; Buxton, Orfeu M. ; Redline, Susan ; Scheer, Frank A J L ; Saxena, Richa. / Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. In: Diabetes. 2016 ; Vol. 65, No. 6. pp. 1741-1751.
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AU - Lane, Jacqueline M.

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AU - Anderson, Clare

AU - Cade, Brian E.

AU - Cain, Sean W.

AU - Czeisler, Charles A.

AU - Gharib, Sina A.

AU - Gooley, Joshua J.

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AU - Patel, Sanjay

AU - Punjabi, Naresh M.

AU - Rajaratnam, Shanthakumar M W

AU - Rueger, Melanie

AU - St. Hilaire, Melissa A.

AU - Santhi, Nayantara

AU - Scheuermaier, Karin

AU - Van Reen, Eliza

AU - Zee, Phyllis C.

AU - Shea, Steven

AU - Duffy, Jeanne F.

AU - Buxton, Orfeu M.

AU - Redline, Susan

AU - Scheer, Frank A J L

AU - Saxena, Richa

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