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Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Metabolic Markers and Type 2 Diabetes in Older Men

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posted on 04.09.2020 by Qian Xiao, Jingyi Qian, Daniel S Evans, Susan Redline, Nancy E. Lane, Sonia Ancoli-Israel, Frank A.J.L. Scheer, Katie Stone, Osteoporotic Fractures in Men (MrOS) Study Group
OBJECTIVE Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes (T2D), yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.

RESEARCH DESIGN AND METHODS Baseline rest-activity rhythms were derived from actigraphy using extended cosine model analysis. Fasting glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were measured from fasting blood at baseline and after ~3.5 years. T2D were defined using self-report, medication use and fasting glucose.

RESULTS In the cross-sectional analysis (n=2,450), lower 24-hour amplitude:mesor ratio (i.e., mean-activity-adjusted rhythm amplitude) and reduced overall rhythmicity, were associated with higher fasting insulin and HOMA-IR (all p-trend < 0.0001), indicating increased insulin resistance. The odds of baseline T2D were significantly higher among those in the lowest quintile of amplitude (OR Q1 vs Q4 (95% CI), 1.63 (1.14, 2.30)) and late acrophase group (OR late vs normal (95% CI), 1.46 (1.04, 2.04)). In the prospective analysis (n=861), multiple rest-activity characteristics predicted a 2-3 fold increase in T2D risk, including a lower amplitude (OR Q1 vs Q4 (95% CI), 3.81 (1.45, 10.00)) and amplitude:mesor ratio (2.79 (1.10, 7.07), reduced overall rhythmicity (3.49 (1.34, 9.10)), and a late acrophase (2.44 (1.09, 5.47)).

CONCLUSIONS Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident T2D.

Funding

The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

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