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

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.