Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I

Abstract

Hyperglycemia and insulin resistance are key players in the development of atherosclerosis and its complications. A large body of evidence suggest that metabolic abnormalities cause overproduction of reactive oxygen species (ROS). In turn, ROS, via endothelial dysfunction and inflammation, play a major role in precipitating diabetic vascular disease. A better understanding of ROS-generating pathways may provide the basis to develop novel therapeutic strategies against vascular complications in this setting. Part I of this review will focus on the most current advances in the pathophysiological mechanisms of vascular disease: (i) emerging role of endothelium in obesity-induced insulin resistance; (ii) hyperglycemia-dependent microRNAs deregulation and impairment of vascular repair capacities; (iii) alterations of coagulation, platelet reactivity, and microparticle release; (iv) epigenetic-driven transcription of ROS-generating and proinflammatory genes. Taken together these novel insights point to the development of mechanism-based therapeutic strategies as a promising option to prevent cardiovascular complications in diabetes.

Coronary Plaque Characteristics in Patients With Diabetes Mellitus Who Presented With Acute Coronary Syndromes

“…Although it is generally accepted that plaque erosion is caused by local endothelial damage rather than vascular inflammation, in a subset of patients with DM, inflammation may still play a significant role even in cases of plaque erosion. In patients with DM, insulin resistance not only impairs endothelial nitric oxide synthase activity, leading to endothelial dysfunction, but also causes reactive oxygen species accumulation triggering proinflammatory gene expression 31. It should be noted, however, that the overall features of vulnerability were still lower in the culprit erosion group compared with the culprit rupture group.…”

Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

“…However, these studies do not allow decide whether hyperglycaemia is a risk factor or only a risk marker [2]. Indeed, hyperglycaemia in patients with T2DM is commonly associated with other well known cardiovascular risk factors such as hypertension, atherogenic dyslipidaemia, abdominal obesity, and metabolic syndrome [20].…”

“…Both type 1 (T1DM) [1] and type 2 (T2DM) [2] diabetes mellitus are associated with endothelial dysfunction and vascular damage. Classically T1DM, which is an almost -pure hyperglycaemic disease‖, is more commonly associated with microangiopathy (retinopathy, nephropathy).…”

Increased Hazard of Myocardial Infarction With Insulin‐Provision Therapy in Actively Smoking Patients With Diabetes Mellitus and Stable Ischemic Heart Disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial

“…The increased rate of macrovascular complications in patients with type 2 diabetes mellitus compared with nondiabetic patients has been attributed to a specific diabetic vasculopathy 6. Dysglycemia caused by insulin resistance initiates structural changes of the vessel wall that culminate in diabetic vascular complications.…”

“…The increased risk is thought to be mediated by a multifactorial diabetic vasculopathy resulting in a prothrombotic coronary vascular milieu 6. Potentially compounding this prothrombotic tendency, treatment of diabetes mellitus with insulin provision pharmacotherapy impairs fibrinolysis.…”