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Plasma concentration of Caspase-8 is associated with short sleep duration and the risk of incident diabetes mellitus

Author:
  • Thomas Svensson
  • Akiko Kishi Svensson
  • Mariusz Kitlinski
  • Peter Almgren
  • Gunnar Engström
  • Jan Nilsson
  • Marju Orho-Melander
  • Peter M Nilsson
  • Olle Melander
Publishing year: 2018-04-01
Language: English
Pages: 1592-1600
Publication/Series: The Journal of clinical endocrinology and metabolism
Volume: 103
Issue: 4
Document type: Journal article
Publisher: Oxford University Press

Abstract english

Context: The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and Caspase-8, a marker of apoptotic activity, have both been implicated in beta cell function.

Objective: To investigate the associations between sleep duration and plasma Caspase-8, and incident DM, respectively.

Design: Prospective cohort study.

Setting: The Malmö Diet and Cancer (MDC) Study is a population-based, prospective study run in the city of Malmö, Sweden.

Participants: 4023 individuals from the MDC Study aged 45-68 years at baseline without a history of prevalent DM, and with information on habitual sleep duration.

Main outcomes: Incident DM.

Results: Mean follow-up time was 17.8 years. Sleep duration was the only behavioural variable significantly associated with plasma Caspase-8. Plasma Caspase-8 was significantly associated with incident DM per standard deviation of its transformed continuous form (hazard ratio [HR]= 1.24, 95% confidence interval [CI] 1.13-1.36), and when dichotomized into high (quartile 4) (HR=1.44, 95%CI: 1.19-1.74) compared to low (quartiles 1-3) concentrations. Caspase-8 interacted with sleep duration; compared to 7-8 hours of sleep and low plasma Caspase-8, individuals with high plasma Caspase-8 and sleep duration <6 hours (HR=3.54, 95%CI: 2.12-5.90), 6-7 hours (HR=1.81, 95%CI: 1.24-2.65), and 8-9 hours (HR=1.54, 95%CI: 1.09-2.18) were at significantly increased risks of incident DM.

Conclusions: Sleep duration is associated with plasma Caspase-8. Caspase-8 independently predicts DM years before disease onset and modifies the effect of sleep duration on incident DM. Future studies should investigate if change of sleep duration modifies plasma concentrations of Caspase-8.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Internal Medicine - Epidemiology
  • ISSN: 1945-7197
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00