Pathogenesis of Diabetic Microvascular Complications

Abstract

Complications of diabetes have been the leading cause of mortality and morbidity in both type 1 and type 2 diabetes. Based on the sites of functional and pathological changes, these complications have been characterized as cardiomyopathy, macrovasculopathy, and microvasculopathy. Multiple clinical studies have shown that glycemic control is by far the most effective approach in the prevention of microvascular and neuropathic complications. However, tight glycemic control is still difficult to achieve using current available regimen, and therefore novel pathogenesis‐based interventions that can prevent and reverse the complications even in the presence of hyperglycemia are needed. Over the past decade, advances in molecular and cellular biological techniques have revealed many potential mechanisms utilized by hyperglycemia to induce its adverse effects. Several mechanisms, including vascular oxidative stress; formation of advanced glycation endproducts; activation of protein kinase C; increased flux through hexosamine pathway; inflammation‐induced vascular pathology; altered expression and actions of growth factors, cytokines, and vasomotor mediators; and increased flux through polyol pathway, have been studied in detail. The identification of such mechanisms has lead to the development of novel pharmacological approaches.

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches

“…Diabetic microvascular disease is pathologically characterized by abnormal growth and permeability of microcirculatory vessels [10]. Arterioles, capillaries and venules are the smallest functional unit of the microvascular bed.…”

“…Unlike macrovessels, the specific role of which is to convey blood to the microcirculation in all organs and tissues, microvessels have specific roles in oxygen and micronutrient delivery. Permeability to small molecules, regulation in the physical dimensions and functional properties of the basement membrane are main microcirculatory features, which vary in different types of microvascular beds, such as the glomeruli, the retina, the myocardium, the skin and the muscle [10]. Apoptotic death of podocytes and pericytes are specific changes in diabetic microvessels, occurring in the kidney and in the retina, respectively [11].…”

The Pathologic Continuum of Diabetic Vascular Disease

“…The clinical problems associated with these changes–retinopathy, nephropathy, and neuropathy–drive a large burden of T2DM morbidity. Microvascular disease also contributes to peripheral vascular disease, reduced myocardium vascularization, and poor wound healing (13). To some extent, diabetic microvascular disease has been overlooked in terms of its clinical impact and research attention.…”

The evolving story of the RAAS in hypertension, diabetes and CV disease – moving from macrovascular to microvascular targets

“…However, microvascular dysfunction is nowadays also regarded to significantly contribute to other diabetic complications such e.g. cardiomyopathy, peripheral vascular disease or poor wound healing [35].…”