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CLINICAL STUDIES

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

Michael J. Mullen, MRCP^*, David Wright, PhD, Ann E. Donald, AVT^*, Sara Thorne, MD, MRCP^*, Hyeyoung Thomson, BSc^* and John E. Deanfield, FRCP^*

^* Vascular Physiology Unit, Great Ormond Street Hospital for Children, London, UK
Department of Statistical Science, University College London, Gower Street, London, UK

Manuscript received October 26, 1999; revised manuscript received January 28, 2000, accepted March 30, 2000.

Reprint requests and correspondence: Dr. Michael J. Mullen, Vascular Physiology Unit, Gt. Ormond Street, Hospital for Children, London, WC1N 3JH, United Kingdom
MichaelJMullen{at}cs.com

OBJECTIVES

We sought to determine the effects of oral L-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 L-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown.

METHODS

In a double-blind, 2 x 2 factorial study, we investigated the effect of L-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 L-arginine levels increased by 247 ± 141% after L-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. L-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, L-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.

Abbreviations and Acronyms   CI = confidence interval   DM = diabetes mellitus   FMD = flow-mediated dilation   GTN = glyceryl trinitrate   GTN-MD = glyceryl trinitrate–mediated dilation   HDL = high density lipoprotein   HMG-CoA = hexamethylglutaryl coenzyme A   LDL = low density lipoprotein   NO = nitric oxide

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