Abstract
Endothelial dysfunction plays a critical role in atherosclerosis progression, leading to cardiovascular complications. There are significant associations between diabetes mellitus, oxidative stress, and endothelial dysfunction. Oxidative stress is increased by chronic hyperglycemia and acute glucose fluctuations induced by postprandial hyperglycemia in patients with diabetes mellitus. In addition, selective insulin resistance in the phosphoinositide 3-kinase/Akt/endothelial nitric oxide (NO) synthase pathway in endothelial cells is involved in decreased NO production and increased endothelin-1 production from the endothelium, resulting in endothelial dysfunction. In a clinical setting, selecting an appropriate therapeutic intervention that improves or augments endothelial function is important for preventing diabetic vascular complications. Hypoglycemic drugs that reduce glucose fluctuations by decreasing the postprandial rise in blood glucose levels, such as glinides, α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitors, and hypoglycemic drugs that ameliorate insulin sensitivity, such as thiazolidinediones and metformin, are expected to improve or augment endothelial function in patients with diabetes. Glucagon-like peptide 1 receptor agonists, metformin, and sodium-glucose cotransporter 2 inhibitors may improve endothelial function through multiple mechanisms, some of which are independent of glucose control or insulin signaling. Oral administration of antioxidants is not recommended in patients with diabetes due to the lack of evidence for the efficacy against diabetic complications.
Highlights
The number of patients with diabetes has been increasing worldwide
These findings suggest that endothelial function is impaired by glucose fluctuations through increased oxidative stress
Metformin has been shown to improve endothelial function in patients without diabetes who have insulin resistance [59]. These findings suggest that metformin improves endothelial function by ameliorating insulin resistance
Summary
The number of patients with diabetes has been increasing worldwide. A pooled analysis showed that the prevalence of diabetes in adults has been increasing, and it was estimated that the number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 [1]. Diabetic vascular complications are major causes of morbidity and mortality in diabetic patients. Macrovascular complications including coronary heart disease, cerebrovascular disease, and peripheral artery disease, are major causes of mortality. A systematic literature review has shown that cardiovascular disease affects approximately 32.2% of patients with type 2 diabetes (21.1% with coronary heart disease, 14.6% with angina, 10.0% with myocardial infarction, and 7.6% with stroke) and that cardiovascular disease is the cause of death in. It is important to understand the mechanisms underlying endothelial dysfunction caused by diabetes mellitus and to select treatments that improve or augment endothelial function for preventing diabetic vascular complications. We discuss the current understanding of the mechanisms of endothelial dysfunction and recommended therapeutic options for improving endothelial function in patients with diabetes mellitus
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