The Association of Measures of Cardiovascular Autonomic Function, Heart Rate, and Orthostatic Hypotension With Incident Glucose Disorders: The Cardiovascular Health Study Diabetes Care 2022;45:2376–2382 | https://doi.org/10.2337/dc22-0553 Joshua I. Barzilay, 1,2 William Tressel, 3 Mary L. Biggs, 3 Phyllis K. Stein, 4 Jorge R. Kizer, 5,6 Sanyog G. Shitole, 5,6 Yakubu Bene-Alhasan, 7 and Kenneth J. Mukamal 7 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 inci- dent diabetes and annual change in fasting glucose (FG) levels as well as with in- sulin 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 not significantly associated with insulin secretion, insu- lin sensitivity, or incident diabetes. We observed no association of HR or orthostatic hypotension with diabetes or FG change. CONCLUSIONS Specific measures of cardiac autonomic function are prospectively related to FG level changes. Strong physiological connections link the autonomic nervous system (ANS) with glu- cose metabolism. Pancreatic islet cells and their blood vessel supply are surrounded by a network of autonomic nerve fibers (1). In healthy individuals, parasympathetic nerve signaling (PNS) triggers early release of insulin from the pancreatic b-cells 1 Division of Endocrinology, Kaiser Permanente of Georgia, Atlanta, GA 2 Division of Endocrinology, Emory School of Medicine, Atlanta, GA 3 Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA 4 Cardiovascular Division, Department of Medicine, Washington University in St. Louis School of Medicine, Saint Louis, MO 5 Cardiology Section, San Francisco VA Health Care System, San Francisco, CA 6 Department of Medicine, University of California, San Francisco, San Francisco, CA 7 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA Corresponding author: Joshua I. Barzilay, joshua. barzilay@kp.org Received 19 March 2022 and accepted 18 June 2022 This article contains supplementary material online at https://doi.org/10.2337/figshare.20286804. © 2022 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www. diabetesjournals.org/journals/pages/license. PATHOPHYSIOLOGY/COMPLICATIONS 2376 Diabetes Care Volume 45, October 2022 Downloaded from http://diabetesjournals.org/care/article-pdf/45/10/2376/701219/dc220553.pdf by guest on 27 November 2023