The cardiovascular effects of insulin.

INTRODUCTION: Cardiovascular disease remains one of the leading causes of morbidity and mortality in diabetes mellitus. A causal link between insulin, atherosclerosis and cardiovascular risk has been investigated at the basic science level and studied in large clinical trials. AREAS COVERED: The cardiovascular actions of insulin and its role at the level of the endothelium will be reviewed. Cardiovascular outcomes in several large diabetes trials where insulin management was prominent will be summarized. EXPERT OPINION: The vascular actions of insulin are complex and mediated primarily via nitric oxide and endothelin-1. It appears that insulin resistance, rather than hyperinsulinemia itself, increases cardiovascular risk. In fact, hyperinsulinemia in the setting of normal beta cell function protects obese and insulin-resistant individuals from type 2 diabetes. Large clinical trials have supported that insulin management is not associated with increased adverse outcomes. A multifactorial approach targeting modifiable risk factors, including smoking cessation, blood pressure and lipid management, reduces cardiovascular risk. Therapy goals should be individualized and hypoglycemia, especially in individuals receiving insulin management, should be strictly avoided.