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.
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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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