Atorvastatin but not image-arginine improves endothelial function in type I diabetes mellitus: a double-blind study

OBJECTIVES We sought to determine the effects of oral image-arginine and the hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial function in young patients with type I diabetes mellitus (DM). BACKGROUND Endothelial dysfunction, a key early event in atherosclerosis, occurs in young patients with type I DM, and its reversal may benefit the progression of vascular disease. Cholesterol reduction in image-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown. METHODS In a double-blind, 2 × 2 factorial study, we investigated the effect of image-arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery vascular function in 84 normocholesterolemic young adults (mean ± SD: age 34 years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96 ± 0.89 mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN) were assessed noninvasively using high resolution ultrasound at baseline and after six weeks of treatment. RESULTS Atorvastatin resulted in a 48 ± 10% decrease in serum LDL cholesterol levels, whereas image-arginine levels increased by 247 ± 141% after image-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. image-Arginine therapy had no significant effect on endothelial function, and there was no significant change in dilation to GTN after either intervention. CONCLUSIONS In young patients with type I DM, improvement in endothelial dysfunction can be demonstrated after just six weeks of treatment with atorvastatin. In contrast to studies of hypercholesterolemia, however, image-arginine had no benefit. Treatment with atorvastatin at an early stage may have an impact on the progression of atherosclerosis in these high risk patients.