Pravastatin, but not atorvastatin, prevented new-onset diabetes and diastolic dysfunction in a rat model of insulin resistance, despite atorvastatin achieving greater lipid lowering.
Does atorvastatin or pravastatin prevent new-onset diabetes and left ventricular diastolic dysfunction in a rat model of type II diabetes?
In a rat model of type II diabetes, pravastatin prevented new-onset diabetes and diastolic dysfunction better than atorvastatin, suggesting statins may have differential effects on insulin resistance independent of their lipid-lowering efficacy.
BACKGROUND: Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). METHODS AND RESULTS: The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-alpha, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography. CONCLUSIONS: The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.
Chen et al. (2006) studied Type II diabetes mellitus and insulin resistance. Atorvastatin vs Pravastatin vs. Untreated control was evaluated on Progressive insulin resistance, new-onset diabetes, and left ventricular diastolic dysfunction. Pravastatin, but not atorvastatin, prevented new-onset diabetes and diastolic dysfunction in a rat model of insulin resistance, despite atorvastatin achieving greater lipid lowering.