Decreased insulin removal contributes to hyperinsulinemia in obesity.

Peripheral plasma insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 7 severely obese and 12 normal weight nondiabetic subjects. The insulin and C-peptide levels as well as incremental areas under the plasma curves were 2--5 times higher in the obese subjects (P less than 0.05). The C-peptide to insulin molar ratios as well as the relation between incremental areas under the plasma curves of the two peptides were used as relative measures of the hepatic insulin extraction. They were both reduced in the obese subjects, which suggests that decreased insulin removal may contribute to the hyperinsulinemia of obesity. Sixty minutes after the oral glucose load, all of the obese patients had higher peripheral venous insulin concentrations compared with those found in normal subjects with similar C-peptide levels. This suggests that the reduced insulin extraction is not entirely explained by increased beta-cell secretory activity, but is also a specific consequence of obesity.