Endothelial Dysfunction in Type 2 Diabetes with an Update on New Interventions

Endothelial dysfunction is an early indicator of diabetic vascular disease and independently predicts cardiovascular risk in patients with type 2 diabetes (T2DM). The pathogenesis of endothelial dysfunction in large and small arteries in T2DM is complex and fundamentally involves uncoupling of endothelial nitric oxide synthase activity, mitochondrial oxidative phosphorylation, and activation of vascular NAD(P)H oxidase, leading to oxidative stress and a vicious cycle leading to progression of arteriopathy. Strategies for treating endothelial dysfunction in T2DM target multiple pathophysiological processes, including dysglycemia, insulin resistance, dyslipidemia, hypertension, oxidative stress, and inflammation. We provide a brief update of the previous chapter in the first edition of this book concerning new therapeutic interventions for improving endothelial dysfunction in T2DM. SGLT-2 inhibitors appear to have beneficial but inconsistent effects on endothelial dysfunction that appear to be dependent on the type of SGLT-2 inhibitor and the background therapy. Although high-dose EPA, PCSK9 inhibitors and GLP-1 agonists have been shown to lower cardiovascular events in patients with T2DM, there have been limited studies of their effects on endothelial dysfunction. A new class of anti-cytokine agents (e.g., IL-6 inhibitors) and colchicine have also been demonstrated to have anti-atherogenic effects in clinical trials, but currently there are a paucity of studies on endothelial dysfunction in patients with T2DM.