Concomitant Reduction of Low-Density Lipoprotein-Cholesterol and Biomarkers of Inflammation with Low-Dose Simvastatin Therapy in Patients with Type 1 Diabetes

Abstract

Cardiovascular disease is a major cause of mortality in type 1 diabetes (TIDM). TIDM is a proinflammatory state. Whereas there is consensus on lipid management in type 2 diabetes, there is a lack of data in type 1 diabetes. In addition to benefits on the lipid profile, statin therapy is antiinflammatory. There are scant data on statin therapy in T1DM. Thus, we tested the effect of simvastatin, compared with placebo, on biomarkers of inflammation and monocyte function in TIDM patients. This was a double-blind, randomized, placebo-controlled study of T1DM patients, randomized to placebo or simvastatin, 20 mg/d for 3 months. The study was conducted at the University of California, Davis, Medical Center. Participants included patients with T1DM. Analytes measured at baseline and 3 months included liver function tests, creatinine, hemoglobin AIC, high-sensitivity C-reactive protein, soluble CD40 ligand, monocyte O(2)(-), cytokines, nuclear factor-kappaB. Simvastatin therapy resulted in significant reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (18% reduction, P < 0.001) and soluble CD40 ligand (22% reduction, P < 0.05), compared with placebo. Simvastatin therapy significantly inhibited lipopolysaccharide-activated monocyte release of O(2)(-) (P < 0.0005), IL-8 (P < 0.03), and TNF (P < 0.02). Simvastatin therapy significantly inhibited monocyte IL-6 release, compared with baseline (P = 0.02). Simvastatin therapy also significantly reduced monocytic nuclear factor-kappaB p65 activity, compared with placebo (P < 0.01). This study demonstrates that simvastatin (20 mg/d) is safe in T1DM patients and has concomitant benefits on the lipid profile and biomarkers of inflammation. These novel findings could have implications for developing policy guidelines for statin therapy in forestalling vascular complications in young T1DM.