Abstract
CONTEXT: There is a paucity of large-scale epidemiological studies on the link between severe hypoglycemia (SH) and corrected QT (QTc) interval prolongation in type 2 diabetes (T2DM). OBJECTIVE: To evaluate the association of SH with QTc prolongation in adults with T2DM. METHODS: Prospective cohort analysis of participants enrolled in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without QTc prolongation at baseline. SH was assessed over a 24-month period. Incident QTc prolongation was ascertained using follow-up electrocardiograms. Modified Poisson regression was used to generate the risk ratio (RR) and 95% CI for QTc prolongation. RESULTS: Among 8277 participants (mean age 62.6 years [SD 6.5], 38.7% women, 62.8% White), 324 had ≥1 SH episode (3.9%). Over a median of 5 years, 517 individuals developed QTc prolongation (6.3%). Participants with SH had a 66% higher risk of QTc prolongation (RR 1.66, 95% CI 1.16-2.38). The incidence of QTc prolongation was 10.3% (27/261) and 14.3% (9/63) for participants with 1 and ≥2 SH, respectively. Compared with no SH, RRs for patients with 1 and ≥2 SH episodes were 1.57 (95% CI 1.04-2.39) and 2.01 (95% CI 1.07-3.78), respectively. Age modified the association of SH with QTc prolongation (PInteraction = .008). The association remained significant among younger participants (<61.9 years [median age]: RR 2.63, 95% CI 1.49-4.64), but was nonsignificant among older participants (≥61.9 years: RR 1.37, 95% CI 0.87-2.17). CONCLUSION: In a large population with T2DM, SH was associated with an increased risk of QTc prolongation independently of other risk factors such as cardiac autonomic neuropathy. The association was strongest among younger participants.