Role of insulin resistance in the association between resting heart rate and type 2 diabetes: A prospective study

Background: Elevated resting heart rate (RHR) is a predictor of incident type 2 diabetes (T2D). Insulin resistance is thought to play a role in this association; however, the extent to which insulin resistance mediates this association is unclear. Methods: 1309 Japanese individuals without diabetes were recruited during 2009-2012 and followed for 5 years, of whom 78 developed T2D, as diagnosed by the 75 g oral glucose tolerance test. Supine RHR was measured by electrocardiography. Using logistic regression analysis, we examined the association between RHR and incident T2D, and interaction with the homeostasis model assessment of insulin resistance (HOMA-IR) index. Causal mediation analysis was applied to decompose the effect of RHR on the outcome and estimate the proportion mediated by the HOMA-IR index. Results: The sex- and age-adjusted cumulative incidence rate of T2D increased with increasing RHR. After adjustment for sex, age, waist circumference, current smoking status, alcohol use, habitual exercise, and cardiovascular disease medications, individuals with a RHR >= 80 bpm, compared with <60 bpm, showed an increased risk of incident T2D [odds ratio (OR), 2.89; 95 % confidence interval (CI), 1.07 to 7.80]. Multivariate adjusted OR for the total effect per 1 SD increase in RHR on incident T2D was 1.37 (95 % CI, 1.01 to 1.74) in the mediation analysis, and the proportion of the total indirect effect mediated by the HOMA-IR index was 27.5 % (95 % CI, 1.5 to 53.5). Conclusions: Approximately 30 % of the effect of RHR on incident T2D was explained by the indirect effect of insulin resistance.