- September 27, 2010
- Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 2010;53(7):1270-87
- DeFronzo RA.
Description of this Publication
The objective of this review was to describe the epidemiological link between prediabetes, diabetes and cardiovascular disease (CVD) and to expose the different mechanisms that could explain this link. It is documented in the epidemiological litterature that diabetes is a cardiovascular equivalent. However, large clinical trials have failed to demonstrate that intensified glycemic control is associated with a reduction in macrovascular complications. Several prospective studies have found that insulin resistance predicts future CVD. In fact, a defect in insulin signalling is known to impair glucose utilization, but also causes hypertension and accelerated atherosclerosis through induction of inflammation and endothelial dysfunction. Moreover, lipotoxicity is a major cause of insulin resistance and impaired beta-cell function in type 2 diabetes and plays a central role in the accelerated CVD. It is also reported that interventions that mobilize ectopic fat such as thiazolidinediones improve muscle insulin sensitivity by reducing lipotoxicity. Thus, insulin resistance and lipotoxicity, in addition to traditional risk factors, appear to be mediators of the increased CVD risk observed in type 2 diabetes.