[Insulin, diabetes and cholesterol metabolism]

Abstract

Cholesterol metabolism is altered in diabetic states. Three main mechanisms seem to be involved in these alterations: a) an increased glycation of cholesterol-rich lipoproteins, b) an insulin-resistant state which is mainly present in overweight type 2 diabetic patients, and c) changes in insulin secretion which depends on the clinical type of diabetes. Insulin per se exerts beneficial effects on the metabolism of cholesterol binding lipoproteins. Despite insulin has a stimulatory influence on the endogenous cholesterol synthesis from Acetyl-CoA, this hormone tends to decrease the LDL cholesterol concentrations through two additional effects: a diminution in the ApoB VLDL synthesis and an increase in the LDL catabolism. In well controlled diabetic patients, plasma concentrations of cholesterol binding lipoproteins are generally found within the normal range. These patients exhibit usually a normal sensitivity to insulin in the liver and peripheral tissues. In this case, the VLDL production is generally decreased, the LDL catabolism is either increased or normal, and therefore the endogenous cholesterol synthesis from Acetyl-CoA remains setted at a normal level. In poorly controlled and/or in insulin resistant diabetic patients, both VLDL cholesterol production and cholesterogenesis are increased, mainly as a consequence of the insulin-resistant state. The excessive glycation of LDL results in a diminution of their catabolism and therefore in an increase of their plasma concentrations. The reverse cholesterol transport pathway is also altered, the modifications being characterized by a diminution in HDL cholesterol concentrations, especially in the HDL2 subfraction. All these changes are certainly involved in the accelerated development of cardio-vascular complications encountered in diabetic patients.