The Association of Measures of Cardiovascular Autonomic Function, Heart Rate, and Orthostatic Hypotension With Incident Glucose Disorders: The Cardiovascular Health Study

OBJECTIVE The autonomic nervous system (ANS) innervates pancreatic endocrine cells, mus-cle, and liver, all of which participate in glucose metabolism. We tested whether measures of cardiovascular ANS function are independently associated with incident diabetes and annual change in fasting glucose (FG) levels as well as with insulin secretion and insulin sensitivity in older adults without diabetes. RESEARCH DESIGN AND METHODS Heart rate (HR) and measures of HR variability (HRV) were derived from 24-h elec-trocardiographic monitoring. Blood pressure, seated and standing, was measured. Cox proportional hazards models and linear mixed models were used to analyze the associations between HRV, HR, and orthostatic hypotension (SBP >20 mmHg decline) and incident diabetes or longitudinal FG change. RESULTS The mean annual unadjusted FG change was 1 mg/dL. Higher detrended fluctuation analyses (DFA) values, averaged over 4–11 (DFA1) or 12–20 beats (DFA2)—reflecting greater versus less organization of beat-to-beat intervals—were associated with less FG increase over time (per 1-SD increment: DFA1: 20.49 mg/dL/year [20.96, 20.03]; DFA2: 20.55 mg/dL/year [21.02, 20.09]). In mutually adjusted analyses, higher SD of the N-N interval (SDNN) was associated with less FG increase over time (per 1-SD increment: SDNN: 20.62 mg/dL/year [21.22, 20.03]). Higher values of DFA1, DFA2, and SDNN were each associated with greater insulin secretion and insulin sensitivity but not with incident diabetes. We observed no association of HR or or-thostatic hypotension with diabetes or FG change. CONCLUSIONS Specific measures of cardiac autonomic function are prospectively related to FG level changes and insulin secretion and action.