Macrovascular Complications in Patients with Diabetes and Prediabetes

Abstract

Diabetes is a significant health problem worldwide, and its association with cardiovascular disease (CVD) was reported in several studies. Hyperglycemia and insulin resistance seen in diabetes and prediabetes lead to an increase in reactive oxygen species, which triggers intracellular molecular signaling. The resulting prothrombotic state and increase in inflammatory mediators expedite atherosclerotic changes and the development of macrovascular complications. Individuals with diabetes or prediabetes have a higher risk of developing myocardial infarction, stroke, and peripheral artery disease. However, no significant difference in cardiovascular morbidity has been observed with tight glycemic control despite a reduction in some CVD outcomes, and the risk of adverse outcomes such as hypoglycemia was increased. Recently, some GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to reduce cardiovascular events and mortality. In this review we give an overview of the risk and pathogenesis of cardiovascular disease among diabetic and prediabetic patients, as well as the implication of recent changes in diabetes management.

Figure 1

The effect of insulin resistance and hyperglycemia in CVD pathogenesis. Insulin resistance is tightly correlated with obesity, which increases FFA and ROS level, both of which contribute to atherosclerotic changes and the development of macrovascular complications. Increased plasma glucose level contributes to increased production of ROS as well, which activates PKCs intracellularly and leads to inflammatory changes and atherosclerosis. FFAs: free fatty acids, ROS: reactive oxygen species, TLR: Toll-like receptor, PI3K: PI3-kinase, PKC: protein kinase C, eNOS: endothelial nitric oxide synthase, NO: nitric oxide, COX-2: cyclooxygenase-2, TXA2: thromboxane A2, PGI₂: prostacyclin, ET-1: endothelin-1.