TYPE 2 DIABETES INCIDENCE IN HYPERTENSIVES WITH DYSLIPIDEMIA ACCORDING TO STATIN INTENSITY REGIMEN, LENGTH OF EXPOSURE AND CARDIORESPIRATORY FITNESS

Objective: Evaluate the incidence of type 2 diabetes mellitus (T2DM) in hypertensive patients with dislipidemia, according to length of statin exposure, statin-intensity regimen, and cardiorespiratory fitness (CRF).Design and method: We included hypertensive patients (n=321,255; age 68.8±10.5 years). Participants were selected if they were: 1) dyslipidemic and treated with statins for >= 6 months; 2) had no T2DM prior to or 6 months post-statin therapy, and 3) completed a standardized exercise treadmill test (ETT) with no evidence of ischemia. We formed age-and-gender-specific CRF categories (quintiles) according to peak metabolic equivalents (METs) achieved during the ETT. We established two statin-intensity categories and six statin-exposure categories ranging from <=1.5 to >15.0 years. Results: During a median follow-up of 11.0 years (3,563,322 person-years of observation), 57,717 participants (18%) developed T2DM, with an average incidence rate of 16.2 events/1,000 person-years. The adjusted risk increased progressively with longer statin exposure and was > 6.0 times higher with statin exposure >15.0 years (hazard ratios [HR] 6.21; 95% confidence interval (CI) 5.52-6.75). High-intensity statin therapy exacerbated the T2DM risk across all statin-exposure groups. T2DM risk declined progressively with higher CRF, regardless the intensity or duration of statin exposure, delaying T2DM onset by 3.0-10.0 years. After >15.0 years of statin exposure, T2DM risk was 52% lower (HR, 0.48; 95% CI, 0.45-0.51) in highly fit individuals compared to least fit. Conclusions: Statin-related T2DM incidence increased progressively with longer exposure and was more pronounced with high-intensity therapy. The risk was mitigated by higher CRF regardless of statin intensity or duration of statin exposure.