Review: The genetics of macrovascular disease in diabetes

Abstract

Patients with diabetes mellitus show an increased risk of developing macrovascular disease. Although common cardiovascular risk factors are abnormally high in patients with type 2 diabetes compared to the general population, they cannot fully explain the high rate of vascular complications. Indeed the occurrence and the severity of such complications are highly heterogeneous even in patients with comparable levels of glycaemic control and similar prevalence of cardiovascular risk factors. Large-vessel atherosclerosis can precede the clinical manifestation of diabetes. This suggests that both atherosclerosis and type 2 diabetes may have common genetic and environmental antecedents. A large body of evidence supports the possible role of genetics in determining the expression of the ischaemic vascular phenotype in diabetic patients, mainly derived from studies in ethnic groups or in first-degree relatives of diabetic patients and from association studies with genetic polymorphisms. Unravelling the polygenic susceptibility factors for macrovascular complications of diabetes is difficult, since diabetes per se has multifactorial inheritance. Direct evidence is largely based on the candidate gene approach in case-control studies. Several systems provide candidate genes that could by themselves or by interacting with other factors, increase the risk of ischaemic vascular disease in diabetic patients mainly related to lipid metabolism, lipoprotein oxidation and haemostatic processes.