Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Metabolic Markers and Type 2 Diabetes in Older Men.

Abstract

Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes, 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. Baseline rest-activity rhythms were derived from actigraphy with use of extended cosine model analysis. With subjects fasting, glucose, insulin, and HOMA of insulin resistance (HOMA-IR) were measured from blood at baseline and after ∼3.5 years. Type 2 diabetes was defined based on self-report, medication use, and fasting glucose. In the cross-sectional analysis (<i>n</i> = 2,450), lower 24-h amplitude-to-mesor ratio (i.e., mean activity-adjusted rhythm amplitude) and reduced overall rhythmicity were associated with higher fasting insulin and HOMA-IR (all <i>P</i> _trend < 0.0001), indicating increased insulin resistance. The odds of baseline type 2 diabetes were significantly higher among those in the lowest quartile of amplitude (Q1) (odds ratio [OR]_{Q1 vs. Q4} 1.63 [95% CI 1.14, 2.30]) and late acrophase group (OR_{late vs. normal} 1.46 [95% CI 1.04, 2.04]). In the prospective analysis (<i>n</i> = 861), multiple rest-activity characteristics predicted a two- to threefold increase in type 2 diabetes risk, including a lower amplitude (OR_{Q1 vs. Q4} 3.81 [95% CI 1.45, 10.00]) and amplitude-to-mesor ratio (OR 2.79 [95% CI 1.10, 7.07]), reduced overall rhythmicity (OR 3.49 [95% CI 1.34, 9.10]), and a late acrophase (OR 2.44 [1.09, 5.47]). Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident type 2 diabetes.