Review

Rev Diabet Stud, 2013, 10(2-3):133-156

DOI 10.1900/RDS.2013.10.133

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Sandra J. Hamilton¹, Gerald F. Watts²

¹Combined Universities Centre for Rural Health, University of Western Australia, Geraldton, Australia
²School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
Address correspondence to: Gerald F. Watts, e-mail: gerald.watts@uwa.edu.au

Manuscript submitted March 20, 2013; resubmitted April 15, 2013; accepted June 13, 2013.

Keywords: type 2 diabetes, dyslipoproteinemia, lipoprotein, vascular disease

Abstract

Type 2 diabetes (T2D) markedly increases the risk of cardiovascular disease. Endothelial dysfunction (ED), an early indicator of diabetic vascular disease, is common in T2D and independently predicts cardiovascular risk. Although the precise pathogenic mechanisms for ED in T2D remain unclear, at inception they probably involve uncoupling of both endothelial nitric oxide synthase activity and mitochondrial oxidative phosphorylation, as well as the activation of vascular nicotinamide adenine dinucleotide phosphate oxidase. The major contributing factors include dyslipoproteinemia, oxidative stress, and inflammation. Therapeutic interventions are designed to target these pathophysiological factors that underlie ED. Therapeutic interventions, including lifestyle changes, antiglycemic agents and lipid-regulating therapies, aim to correct hyperglycemia and atherogenic dyslipidemia and to improve ED. However, high residual cardiovascular risk is seen in both research and clinical practice settings. Well-designed studies of endothelial function in appropriately selected volunteers afford a good opportunity to test new therapeutic interventions, paving the way for clinical trials and utilization in the care of the diabetic patient. However, based on the results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled low-density lipoprotein cholesterol.

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