Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study.
OBJECTIVE
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, 2x2 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.
Mullen
M J
MJ
Vascular Physiology Unit, Great Ormond Street Hospital for Children, London, United Kingdom. MichaelJMullen@cs.com
Wright
D
D
Donald
A E
AE
Thorne
S
S
Thomson
H
H
Deanfield
J E
JE
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D000069059:Atorvastatin; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D001120:Arginine; D000069059:Atorvastatin