The Association Among Autonomic Nervous System Function, Incident Diabetes, and Intervention Arm in the Diabetes Prevention Program

The Association Among Autonomic Nervous System Function, Incident Diabetes, and Intervention Arm in the Diabetes Prevention Program Mercedes R. Carnethon , PHD 1 , Ronald J. Prineas , MD, PHD 2 , Marinella Temprosa , MS 3 , Zhu-Ming Zhang , MD 2 , Gabriel Uwaifo , MD 4 , Mark E. Molitch , MD 5 and for the Diabetes Prevention Program Research Group 1 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 2 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 3 Biostatistics Center, George Washington University, Rockville, Maryland 4 MedStar Research Institute, Hyattsville, Maryland 5 Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois Address correspondence and reprint requests to Dr. Mercedes Carnethon, DPP Coordinating Center, 6110 Executive Blvd., Suite 750, Rockville, MD 20852. E-mail: dppmail{at}biostat.bsc.gwu.edu Abstract OBJECTIVE —Autonomic nervous system dysfunction, a correlate of obesity and poor cardiorespiratory fitness, is associated with the development of diabetes. We tested whether estimates of autonomic nervous system function improved in the intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention Program (DPP) and whether baseline or a change in autonomic nervous system function was associated with the development of diabetes over 3.2 years. RESEARCH DESIGN AND METHODS —In 2,980 DPP participants, 12-lead electrocardiograms were measured at baseline and annually. Heart rate, heart rate variability (HRV), and QT duration were used to estimate fitness and autonomic nervous system function. RESULTS —In the lifestyle arm, heart rate and QT indexes decreased, and HRV increased over time. The magnitude of decline in heart rate and QT duration was substantially smaller in the other arms, whereas HRV did not increase. Baseline heart rate was the only index significantly ( P < 0.05) associated with incident diabetes after adjustment for demographics and weight change (hazard ratio for lifestyle and metformin arms = 1.19 and 1.17 per 10.6 beats/min, respectively). Decreases in heart rate and QT indexes and increases in HRV over time were associated with a lower risk of developing diabetes. The protective association between decreased heart rate and incident diabetes in the lifestyle arm remained significant after accounting for change in weight and physical activity. CONCLUSIONS —Indexes that reflect autonomic function and fitness improved (i.e., heart rate decreased and HRV increased) in the lifestyle modification arm of the DPP. Improvements in these indexes are inversely associated with the development of diabetes independent of weight change. DPP, Diabetes Prevention Program ECG, electrocardiogram HRV, heart rate variability QTc, Bazett’s correction QTI, QT index rMSSD, root mean square of successive differences between all normal-to-normal R-R intervals SDNN, standard deviation of all normal-to-normal R-R intervals Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted January 5, 2006. Received September 14, 2005. DIABETES CARE