Cerivastatin Improves Insulin Sensitivity and Insulin Secretion in Early-State Obese Type 2 Diabetes

Abstract

In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months. The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp (EHC; 5.4 mmol/l; 80 mU · m⁻² · min⁻¹) was increased by cerivastatin treatment (66.39 ± 3.9 nmol · lean body mass [LBM]⁻¹ · min⁻¹ · pmol⁻¹ · l⁻¹) as compared with placebo (58.37 ± 3.69 nmol · LBM⁻¹ · min⁻¹ · pmol⁻¹ · l^{− 1}; P < 0.01) by 13.7%. Glucose oxidation during EHC was significantly higher with statin treatment (16.1 ± 1.37 μmol · LBM⁻¹ · min⁻¹) as compared with placebo (14.58 ± 1.48 μmol · LBM⁻¹ · min⁻¹; P < 0.05). During hyperinsulinemia (∼800 pmol/l) in EHC steady-state, lipid oxidation was significantly decreased and respiratory quotient was significantly increased with statin treatment (0.33 ± 0.05 mg · LBM⁻¹ · min^{− 1}, 0.94 ± 0.01) as compared with placebo (0.48 ± 0.06 mg · LBM⁻¹ · min⁻¹, 0.91 ± 0.01; P < 0.01 and P < 0.05, respectively). During statin treatment, the first-phase insulin response increased from 2.07 ± 0.28 to 2.82 ± 0.38 pmol · l⁻¹ · pmol⁻¹ (P < 0.05). The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp (20 mmol/l) was unchanged. In conclusion, this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes.