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

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Objective: To describe 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: T2D individuals on metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at baseline, 2-, and 4-year study visits and analyzed for minor/major abnormalities and CAN assessed with heart rate variability (HRV) in 4769 participants. Incidence of new major/minor/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 57.2 ± 10.0 years old, 36.3% women, had diabetes duration 4.3 ± 2.8 years, and HbA1c 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 liraglutide vs. non-liraglutide groups (9% vs. 13%; p=0.03). The incidence of CAN did not differ between liraglutide vs. non-liraglutide groups across visits (p=0.42); however, one measure of HRV (standard deviation of normal-to-normal R-R intervals) was higher at year 2 in liraglutide vs. non-liraglutide groups (p=0.02). Conclusions: ECG abnormalities, including those reflecting CAN, are common in T2D <10 years, more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.

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