Diabetes Incidence According to Statin Intensity Regimen, Body Mass Index, and Cardiorespiratory Fitness

To evaluate the association between statin therapy, cardiorespiratory fitness (CRF), body mass index (BMI), and type 2 diabetes mellitus (T2DM).

A nationwide cohort of dyslipidemic patients (n=311,269; age 60.8±9.2 years) was treated with statins for 6 months or longer, with no T2DM before statin initiation. All completed a standardized exercise treadmill test between October 1, 1999, and September 3, 2020, with no evidence of ischemia. We formed age- and gender-specific five CRF categories according to peak metabolic equivalents (METs) achieved, four BMI categories, and two statin intensity categories.

During a median follow-up of 10.9 years (3,421,650 person-years of observation), 56,994 developed T2DM (incidence rate 16.7 events/1000-person-years). The adjusted risk was 23% higher in patients on high-intensity compared with those on low-intensity statins (HR, 1.23; 95% CI, 1.21 to 1.25). The T2DM risk increased progressively with higher BMI and high-intensity statin regimen to a 4.44-fold increase (HR, 4.44; 95% CI, 4.22 to 4.67) for obese patients. Conversely, the CRF-T2DM association was inverse and graded regardless of BMI or static-intensity regimen and was approximately 30% to 60% lower risk for patients achieving greater than or equal to 8.4±1.2 METs. Compared with least-fit/low-intensity statin-treated patients, T2DM risk was 21% higher for least-fit/high-intensity statin-treated patients (HR, 1.21; 95% CI, 1.18 to 1.25), and 47% lower (HR, 0.53; 95% CI, 0.51 to 0.56) in highly fit/high-intensity statin-treated patients.

High-intensity statin therapy was associated with an increased risk of T2DM. The risk increased progressively with higher BMI and decreased with higher CRF. Strategies to improve fitness and weight loss in patients on high-intensity statins can potentially lower T2DM risk.