Can weight gain in healthy, nonobese volunteers be predicted by differences in baseline plasma insulin concentration?

In this study, we have evaluated the effect, over approximately 14 yr, of differences in baseline degree of hyperinsulinemia on weight gain in 647 healthy, nonobese factory workers. The subjects were divided into 4 quartiles, on the basis of their plasma insulin response to an oral glucose challenge, in 1981. At that time, the mean (+/-SD) plasma insulin concentration, 2 h after the glucose challenge, varied from 18+/-5 to 106+/-42 microU/mL. Despite this approximate 6-fold difference in plasma insulin response at baseline, the weight gain over the period of observation was similar in all quartiles, with mean (+/-SD) increments (kg) of 1.8+/-5.1, 1.6+/-5.3, 2.3+/-5.2, and 2.3+/-5.7, going from the lowest quartile to the highest quartile, in terms of insulin concentration. Furthermore, when the population was considered as a whole, there was no correlation between baseline degree of hyperinsulinemia and change in either absolute (r = 0.004) or percent (r = 0.003) weight gain. Finally, there was no difference in the number of individuals who gained more than 4.5 kg, as a function of their baseline insulin response. Consequently, we conclude that 6-fold differences in plasma insulin responses to glucose do not predict weight gain in a healthy, nonobese population.

Comparison of fasting plasma leptin concentrations in healthy subjects with high and low plasma insulin.

This study was initiated to evaluate the role of hyperinsulinemia in the regulation of fasting plasma leptin. We measured plasma leptin and insulin concentrations in 404 healthy nondiabetic subjects. For analytical purposes, the population was divided into quartiles on the basis of the lowest (quartile 1) and highest (quartile 4) plasma insulin response to oral glucose, and fasting plasma leptin values in these 2 dichotomous groups were compared. The total plasma integrated insulin response was 4-fold greater in quartile 4, associated with significantly higher (P < .001) fasting plasma leptin (12.60+/-0.85 v8.53+/-0.56 ng/mL). Fasting plasma leptin concentrations remained significantly higher in the hyperinsulinemic quartile when comparisons were made after subdividing the population on the basis of gender, body mass index (BMI), or waist to hip ratio (WHR). These results demonstrate that fasting plasma leptin concentrations are significantly higher in hyperinsulinemic individuals, and this difference is independent of either overall or central obesity.

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.