Metabolism - Clinical and Experimental
Volume 58, Issue 9 , Pages 1270-1276, September 2009

Oral l-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass

  • Pietro Lucotti

      Affiliations

    • Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Lucilla Monti

      Affiliations

    • Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy
    • Diabetes Core Lab, Metabolic and Cardiovascular Science Division, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Emanuela Setola

      Affiliations

    • Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Giovanni La Canna

      Affiliations

    • Cardiothoracovascular Department, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Alessandro Castiglioni

      Affiliations

    • Cardiothoracovascular Department, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Alessandra Rossodivita

      Affiliations

    • Cardiothoracovascular Department, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Maria Grazia Pala

      Affiliations

    • Cardiothoracovascular Department, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Francesco Formica

      Affiliations

    • Cardiac Surgery Clinic, University of Milano-Bicocca, 20052 Monza, Italy
  • ,
  • Giovanni Paolini

      Affiliations

    • Cardiac Surgery Clinic, University of Milano-Bicocca, 20052 Monza, Italy
  • ,
  • Alberico Luigi Catapano

      Affiliations

    • Department of Pharmacological Sciences, University of Milan, 20100 Milan, Italy
  • ,
  • Emanuele Bosi

      Affiliations

    • Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy
    • Vita-Salute University, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • Ottavio Alfieri

      Affiliations

    • Cardiothoracovascular Department, Scientific Institute San Raffaele, 20132 Milan, Italy
    • Vita-Salute University, Scientific Institute San Raffaele, 20132 Milan, Italy
  • ,
  • PierMarco Piatti

      Affiliations

    • Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy
    • Vita-Salute University, Scientific Institute San Raffaele, 20132 Milan, Italy
    • Corresponding Author InformationCorresponding author. Internal Medicine Department, Cardio-Diabetes Trials Unit, Scientific Institute San Raffaele, 20132 Milan, Italy. Tel.: +39 0226432819; fax: +39 0226433839.

Received 19 December 2008; accepted 26 March 2009. published online 10 July 2009.

Abstract 

It is known that l-arginine treatment can ameliorate endothelial dysfunction and insulin sensitivity in type 2 diabetes mellitus patients, but little is known on l-arginine effects on these variables in nondiabetic patients with stable cardiovascular disease (coronary artery disease). We evaluated the effects of long-term oral l-arginine treatment on endothelial dysfunction, inflammation, adipokine levels, glucose tolerance, and insulin sensitivity in these patients. Sixty-four patients with cardiovascular disease previously submitted to an aortocoronary bypass and not known for type 2 diabetes mellitus had an oral glucose load to define their glucose tolerance. Thirty-two patients with nondiabetic response were eligible to receive, in a double-blind randomized parallel order, l-arginine (6.4 g/d) or placebo for 6 months. An evaluation of insulin sensitivity index during the oral glucose load, markers of systemic nitric oxide bioavailability and inflammation, and blood flow was performed before and at the end of the treatment in both groups. Compared with placebo, l-arginine decreased asymmetric dimethylarginine levels (P < .01), indices of endothelial dysfunction, and increased cyclic guanosine monophosphate (P < .01), l-arginine to asymmetric dimethylarginine ratio (P < .0001), and reactive hyperemia (P < .05). Finally, l-arginine increased insulin sensitivity index (P < .05) and adiponectin (P < .01) and decreased interleukin-6 and monocyte chemoattractant protein–1 levels. In conclusion, insulin resistance, endothelial dysfunction, and inflammation are important cardiovascular risk factors in coronary artery disease patients; and l-arginine seems to have anti-inflammatory and metabolic advantages in these patients.

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PII: S0026-0495(09)00137-1

doi:10.1016/j.metabol.2009.03.029

Metabolism - Clinical and Experimental
Volume 58, Issue 9 , Pages 1270-1276, September 2009