Risk of elevated resting heart rate on the development of type 2 diabetes in patients with clinically manifest vascular diseases

OBJECTIVE: Sympathetic nerve activation is causally related to insulin resistance as both a cause and a consequence. Resting heart rate (RHR) reflects sympathetic nerve activity. We investigated the effect of RHR on the incidence of type 2 diabetes mellitus (T2DM) in patients with clinically manifest vascular diseases. DESIGN: Data were used from the second manifestations of arterial disease (SMART) study: a prospective cohort study of patients with clinically manifest vascular diseases (n=3646). METHODS: RHR was obtained using an electrocardiogram. Patients were followed up for incident type 2 diabetes (n=289) during a median period of 5.5 (interquartile range 3.2-8.4) years. The relation between RHR and incident T2DM was estimated by Cox proportional hazard analysis. As age was an effect modifier (P=0.048), analyses were stratified for age. RESULTS: Patients in quartile 4 (Q4) of RHR had a 65% increased risk of T2DM compared with those in Q1 (reference; hazard ratios (HR), 1.65; 95% confidence interval (95% CI), 1.15-2.36) adjusted for age, gender, smoking, estimated glomerular filtration rate, systolic blood pressure, location of vascular disease, and antihypertensive medication. Every 10 beats per minute (bpm) increase in RHR increased the risk for T2DM with 10% (HR, 1.10; 95% CI, 1.00-1.21) in the total population. This risk was particularly high in subjects aged 55-63 years (per 10 bpm: HR, 1.22; 95% CI, 1.04-1.43) and was independent of the location of vascular disease and beta-blocker use. CONCLUSIONS: Increased RHR, an indicator of sympathetic nerve activity, is associated with an increased risk for T2DM in patients with manifest vascular diseases, particularly in middle-aged patients.