93 Insulin resistance is associated with QT prolongation in the 1946 british birth cohort

Background

Diabetic patients are at increased risk of sudden cardiac death and an association with prolonged heart rate-corrected QT interval (QTc) has been demonstrated. However, the relationship of QTc with circulating blood markers of insulin resistance in the general population is not well understood. The aim of this study was to examine the association between blood biomarkers and QTc interval of insulin resistance in an older age, population-based cohort.

Methods

Participants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort (figure 1). The following insulin resistance biomarkers were measured from blood samples at 60-64 years (exposures): insulin, pro-insulin, insulin-like growth factor-I and II (IGF-I/II), IGF binding protein 3, leptin, adiponectin, glucose and glycated haemoglobin A1c. Additionally IGF-I/II was measured at age 53. QTc interval (outcome) was recorded from resting 12-lead electrocardiograms at age 60-64. Generalised linear models were used to statistically analyse the data, and adjustment was made for relevant demographic and health-related confounders. The multivariable analysis was repeated after eliminating participants with a history of cardiovascular disease as a sensitivity analysis. A directed acyclic graph was created to summarise the assumptions about the relationship between insulin resistance biomarkers and QTc (figure 2).

Results

A total of 1448 participants were included (48.3% men; QTc mean [interquartile range] 414ms [26ms]). Leptin showed a non-linear inverse U-shaped relationship with QTc, so a quadratic polynomial was used. On univariate analysis QTc prolongation was significantly associated with low IGF-I, low leptin and high adiponectin levels (all p<0.05), but not associated with IGF-II, insulin, pro-insulin and HbA1c (even after removing participants that have not fasted) at 60-64 years. In fully adjusted multivariable models (table 1), associations persisted for IGF-I (β -0.04 ms/ng/ml; 95% confidence interval [CI] -0.06, -0.01; p= 0.001) and leptin (β -76.44 ms/ng/ml; 95% CI -128.61, -23.77; p=0.004), even after removing participants with cardiovascular disease (IGF-I: β -0.03 ms/ng/ml; 95% CI -0.05, -0.004; p=0.021; leptin: β -82.41 ms/ng/ml; 95% CI -132.38, -31.92; p=0.001).

Conclusion

Low levels of IGF-I and leptin (but not high leptin), representing insulin resistance, associate with prolonged QTc interval in older age. As QTc prolongation signals increased risk for sudden death even in apparently healthy people, public health efforts should be stepped up to combat the emergence of insulin resistance. Further research is needed to understand the potential mechanisms involved.

Conflict of Interest

N/A