Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort

Rodica Pop-Busui, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health & Science University, Portland, OR.
Samuel P. Rosin, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Nicole M. Butera, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Heidi Krause-Steinrauf, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Hiba Abou Assi, Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC.
Rajesh K. Garg, Department of Medicine, University of Miami, Miami, FL.
Silvio E. Inzucchi, Section of Endocrinology, Yale School of Medicine, New Haven, CT.
Aimee Katona, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Janet B. McGill, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine in St. Louis, St. Louis, MO.
Sunder Mudaliar, VA San Diego Healthcare System, San Diego, CA.
David S. Schade, Division of Endocrinology, University of New Mexico School of Medicine, Albuquerque, NM.
Elizabeth R. Seaquist, Department of Medicine, University of Minnesota, Minneapolis, MN.
Margaret Tiktin, Cleveland VA Northeast Ohio Healthcare System, Cleveland, OH.
Elsayed Z. Soliman, Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention and Department of Internal Medicine-Cardiology Section, Wake Forest School of Medicine, Winston-Salem, NC.
Jennifer B. Green, Duke Clinical Research Institute and Division of Medicine, Endocrinology, Metabolism, and Nutrition, Duke University School of Medicine, Durham, NC.

Document Type

Journal Article

Publication Date

9-23-2025

Journal

Diabetes care

DOI

10.2337/dc25-1087

Abstract

OBJECTIVE: To describe the prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG-derived cardiovascular autonomic neuropathy (CAN) in the GRADE cohort of adults with type 2 diabetes (T2D) <10 years. RESEARCH DESIGN AND METHODS: Individuals with T2D taking metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at the baseline, 2-year, and 4-year study visits and analyzed for minor and major abnormalities and CAN assessed with heart rate variability (HRV) in 4,769 participants. Incidence of new major, minor, and any ECG abnormalities and CAN by treatment group was analyzed using logistic repeated-measures models at years 2 and 4 adjusted for baseline risk factors. RESULTS: At baseline, participants were a mean age of 57.2 ± 10.0 years, 36.3% were women, mean diabetes duration was 4.3 ± 2.8 years, and mean HbA1c was 7.5 ± 0.5%. Participants with ECG abnormalities at baseline (57.1%) and ECG-derived CAN (52.8%) were older and had more severe cardiovascular risk factors. The incidence of minor and major ECG abnormalities was similar among all treatment groups. However, at year 4, major ECG abnormalities were fewer in the liraglutide versus nonliraglutide groups (9% vs. 13%; P = 0.03). The incidence of CAN did not differ between the liraglutide and nonliraglutide groups across visits (P = 0.42); however, one measure of HRV (SD of normal-to-normal R-R intervals) was higher at year 2 in the liraglutide versus nonliraglutide groups (P = 0.02). CONCLUSIONS: ECG abnormalities, including those reflecting CAN, are common in individuals with T2D <10 years and more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.

Department

Biostatistics and Bioinformatics

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