Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor

Markus C. Stühlinger, Fahim Abbasi, James W. Chu, Cindy Lamendola, Tracey L. McLaughlin, John P. Cooke, Gerald M. Reaven, Philip S. Tsao

Research output: Contribution to journalArticle

531 Scopus citations

Abstract

Context: Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and increased risk of cardiovascular disease. Several cardiovascular risk factors are associated with reduced sensitivity to insulin, but elevated ADMA concentrations have not been fully linked to the metabolic syndrome. Objective: To evaluate the relationship between insulin sensitivity and plasma ADMA concentrations, and to determine whether a pharmacological treatment that increases insulin sensitivity would also modulate ADMA concentrations. Design, Setting, and Subjects: Cross-sectional study, containing a nonrandomized controlled trial component, of 64 healthy volunteers without diabetes (42 women, 22 men; 48 with normal blood pressure and 16 with hypertension), which was conducted at a university medical center between October 2000 and July 2001. Intervention: Rosiglitazone (4 mg/d for 4 weeks and then 4 mg twice daily for 8 weeks), an insulin-sensitizing agent, was given to 7 insulin-resistant subjects with hypertension. These subjects were studied before and after 12-week treatment. Main Outcome Measures: Insulin sensitivity measured by the insulin suppression test, and fasting plasma levels of low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, glucose, insulin, and ADMA concentrations. Results: Plasma ADMA concentrations were positively correlated with impairment of insulin-mediated glucose disposal in nondiabetic, normotensive subjects (r=0.73; P<.001). Consistent with the metabolic syndrome, ADMA levels were also positively correlated with fasting triglyceride levels (r=0.52; P<.001) but not with low-density lipoprotein cholesterol levels (r=0.19; P=.20). Plasma ADMA concentrations increased in insulin-resistant subjects independent of hypertension. Pharmacological treatment improved insulin sensitivity and reduced mean (SD) plasma ADMA concentrations from 1.50 (0.30) to 1.05 (0.33) μmol/L (P=.001). Conclusion: A significant relationship exists between insulin resistance and plasma concentrations of ADMA. Pharmacological intervention with rosiglitazone enhanced insulin sensitivity and reduced ADMA levels. Increases in plasma ADMA concentrations may contribute to the endothelial dysfunction observed in insulin-resistant patients.

Original languageEnglish (US)
Pages (from-to)1420-1426
Number of pages7
JournalJournal of the American Medical Association
Volume287
Issue number11
DOIs
StatePublished - Mar 20 2002

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor'. Together they form a unique fingerprint.

Cite this