Plasma nitric oxide concentrations are elevated in insulin-resistant healthy subjects

The goal of this study was to compare plasma nitric oxide (NO) concentrations in healthy subjects, defined as either insulin-resistant or insulin-sensitive on the basis of the plasma insulin response to a 75-g oral glucose challenge. For this purpose, 404 healthy subjects were divided into quartiles on the basis of the plasma insulin response to glucose, and 49 individuals were selected from the quartile with the lowest insulin response and 49 from the quartile with the highest insulin response. The two groups of 49 each were selected to be essentially identical in terms of age, gender distribution, body mass index (BMI), and waist to hip ratio (WHR). The quartile with the greatest insulin response also had a significantly higher plasma glucose response to oral glucose, faster heart rate, higher blood pressure, and the combination of higher triglyceride and lower high-density lipoprotein (HDL) cholesterol concentrations. In addition to the latter changes, previously shown to be associated with hyperinsulinemia, NO concentrations were also higher in the hyperinsulinemic group. It is speculated that this increase in the NO concentration in hyperinsulinemic and presumably insulin-resistant, subjects represents a compensatory effort to overcome the untoward effects of insulin resistance and/or hyperinsulinemia.