Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes

Ali Fard, Catherine H. Tuck, Joshua A. Donis, Robert Sciacca, Marco R. Di Tullio, Henry D. Wu, Todd A. Bryant, Niem Tzu Chen, Margarita Torres-Tamayo, Ravichandran Ramasamy, Lars Berglund, Henry N. Ginsberg, Shunichi Homma, Paul J. Cannon

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Asymmetric dimethylarginine (ADMA), a compound detectable in human plasma, is an endogenous inhibitor of NO synthase. Endothelial dysfunction is an early event in atherogenesis, and large-vessel atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Fifty patients with type 2 diabetes mellitus were studied at baseline and 5 hours after ingestion of a high-fat meal. Plasma ADMA measured by using high-performance liquid chromatography increased from 1.04±0.99 to 2.51±2.27 μmol/L (P<0.0005). Brachial arterial vasodilation after reactive hyperemia, a NO-dependent function, measured by high-resolution ultrasound, decreased from 6.9±3.9% at baseline to 1.3±4.5% (P<0.0001). These changes occurred in association with increased plasma levels of triglycerides and very low density lipoprotein triglycerides, with reduced low density lipoprotein cholesterol and high density lipoprotein cholesterol, and with no changes in total cholesterol. The increase in plasma ADMA in response to a high-fat meal was significantly and inversely related to the decrease in percent vasodilation. In 10 of the subjects studied with a similar protocol on another day, no significant changes in the brachial artery flow responses or in plasma ADMA were observed 5 hours after ingestion of a nonfat isocaloric meal. The data suggest that ADMA may contribute to abnormal blood flow responses and to atherogenesis in type 2 diabetics.

Original languageEnglish (US)
Pages (from-to)2039-2044
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number9
StatePublished - 2000
Externally publishedYes

Keywords

  • Asymmetric dimethylarginine
  • Diabetes mellitus
  • Nitric oxide
  • Triglyceridemia
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Fard, A., Tuck, C. H., Donis, J. A., Sciacca, R., Di Tullio, M. R., Wu, H. D., Bryant, T. A., Chen, N. T., Torres-Tamayo, M., Ramasamy, R., Berglund, L., Ginsberg, H. N., Homma, S., & Cannon, P. J. (2000). Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(9), 2039-2044.