Abstract 816: Predictors of Incident Diabetes in the TNT Trial

Abstract

Background: The effect of statin therapy on the development of diabetes mellitus (DM) is not well understood. While data from the WOSCOPS trial showed a 30% reduction in DM with pravastatin treatment, rosuvastatin in JUPITER was associated with higher rates of incident DM. The purpose of this post-hoc analysis of the Treating to New Targets (TNT) trial was to examine predictors of incident DM in subjects treated with atorvastatin.

Methods: Among 10,001 patients with stable documented CHD randomized to atorvastatin 80 or 10 mg/day, 7,595 patients without baseline DM and with ≥2 post-baseline glucose measurements were included in this analysis. The primary end point was new onset DM, defined by adverse event reporting or ≥2 post-baseline glucose measurements ≥7.0 mmol/L and at least 1 post-baseline glucose > 2 mmol/L above baseline.

Results: The mean age was 61 years, and 83% were male. Over a median follow-up of 4.9 years, 8.7% of subjects developed incident DM. In univariate analyses, baseline fasting glucose, body-mass index (BMI), white-blood cell count, systolic blood pressure, total and HDL cholesterol, triglyceride level, and hypertension were predictors of incident DM (all p<0.0001). After adjustment, independent predictors of new onset DM included baseline glucose, BMI, and hypertension. Every 1 mmol/L increase in baseline glucose was associated with a five-fold increased risk of DM (HR=5.29, 95% CI 4.6 – 6.1, p<0.0001). BMI increased the risk of DM by 20% (HR 1.20 per 3 kg/m2 increase, 95% CI 1.15–1.25, p<0.0001), as did a history of hypertension (HR 1.22, 95% CI 1.03–1.44, p=0.02). Of 3798 subjects randomized to 80mg atorvastatin, 351 (9.24%) developed DM, compared with 308 of 3797 (8.11%) subjects treated with 10mg atorvastatin (HR 1.15, 95% CI 0.98 –1.34, p=0.08). After adjustment for clinical covariates, high- versus low-dose atorvastatin treatment did not predict incident DM (HR=1.10, 95% CI 0.94 –1.29, p=0.23).

Conclusions: In patients with stable CHD, higher baseline fasting glucose and features of the metabolic syndrome were predictive of incident DM. A trend toward greater new-onset DM seen with high-dose atorvastatin was attenuated after adjustment for other clinical covariates.