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

J Am Coll Cardiol. 2000 Aug;36(2):410-6. doi: 10.1016/s0735-1097(00)00743-9.


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, 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arginine / pharmacology*
  • Atorvastatin
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Female
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Pyrroles / pharmacology*
  • Vasodilation / drug effects*


  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Arginine
  • Atorvastatin