Drug treatments to restore vascular function and diabesity

Abstract

Over the last decades, an escalating rate of type 2 diabetes has paralleled an epidemic rise in the prevalence of obesity. Both diabetes and obesity confer an increased risk of cardiovascular comorbidities, including hypertension, coronary artery disease and stroke. Vascular dysfunction, represented by impaired endothelial release of vasodilator substances or defective smooth muscle vasodilator reactivity, is the early stage of the process leading to atherosclerosis and a common finding in patients with diabesity. It is understandable, therefore, that effective treatments for diabesity should restore vascular function to prevent the development of cardiovascular disease. Recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection. Thus, glucose control with either DDP-4 inhibitor or GLP-1 receptor therapies seems associated with favorable effects on vascular function in diabetes and the metabolic syndrome. Another mechanism to counter excess plasma glucose and reduce body weight in these patients may rely on drug therapies targeting gut hormones, as suggested by the efficacy of bariatric surgery to produce both sustained weight loss and high diabetes remission rates. Also, as knowledge of the multifaceted vascular actions of adipokines and their dysregulation in patients with diabesity increases, these substances become attractive targets for treatments aimed at cardiovascular prevention. The increasing coexistence of diabetes and obesity presents complex treatment challenges owing to the elevated risk of developing cardiovascular complications. Hence, therapeutic strategies integrating glycemic control, weight loss and vascular protection are of the greatest importance to successfully counteract the health and economic burden posed by diabesity.