Highlights In this prospective study of ACCORD trial participants, investigators monitored patients with diabetes for 24 months for episodes of severe hypoglycemia and measured incident QTc prolongation. Three different regression models, accounting for several different covariates in each model, including but not limited to age, sex, treatment, and BMI, were used to assess significance. The results showed that people with severe hypoglycemia were more likely to be older, black, and on insulin compared to people without severe hypoglycemia. However, in all regression models, severe hypoglycemia was associated with an increased relative risk of QTc prolongation. The study results suggest that severe hypoglycemia may be associated with an increased risk of QTc interval prolongation. The authors note that this may explain the increase in cardiovascular deaths associated with severe hypoglycemia. |
Summary
Context
There is a paucity of large-scale epidemiological studies on the link between severe hypoglycemia (SH) and corrected QT interval (QTc) prolongation in type 2 diabetes (T2DM).
Aim
To evaluate the association of severe hypoglycemia (SH) with QTc prolongation in adults with T2DM.
Study design
Prospective cohort analysis of participants enrolled in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without QTc prolongation at baseline. SH was evaluated over a 24-month period .
Incident QTc interval prolongation was determined by follow-up electrocardiograms. Modified Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI) for QTc prolongation.
Results
Among 8277 participants (mean age 62.6 years [SD: 6.5], 38.7% female, 62.8% white), 324 had ≥1 SH (3.9%).
Over a median of 5 years , 517 people developed QTc prolongation (6.3%).
Participants with SH had a 66% increased risk of QTc prolongation (RR 1.66, 95% CI 1.16 to 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, the RRs for patients with 1 and ≥2 SH 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=0.008). The association remained significant among younger participants (<61.9 years [median age]: RR 2.63, 95% CI 1.49-4.64), but was not significant among older participants (≥61.9 years: RR 1.37, 95% CI 0.87-2.17).
Conclusion
In a large T2DM population, severe hypoglycemia (SH) was associated with an increased risk of QTc prolongation independently of other risk factors, such as cardiac autonomic neuropathy. The association was stronger among younger participants.
