Insulin resistance does not change the ratio of proinsulin to insulin in normal volunteers.

Plasma glucose, insulin, and proinsulin concentrations were measured before and after an oral glucose challenge in 57 nondiabetic individuals. In addition, insulin-mediated glucose disposal was estimated by determining the steady state plasma glucose (SSPG) concentration after a 180-min iv infusion of somatostatin, insulin, and glucose. The plasma glucose concentration after oral glucose administration was used to divide the population into those with normal (n = 36) or impaired glucose tolerance (IGT; n = 21), and the 36 normal glucose-tolerant individuals were further subdivided into an insulin-sensitive (SSPG, < 9.0 mmol/L; n = 15) and an insulin-resistant (SSPG, > 10 mmol/L; n = 21) group. Fasting and postglucose load insulin concentrations were similar in the normal glucose-tolerant insulin-resistant and IGT groups, but were significantly higher (P < 0.02- < 0.001) than those in normal glucose-tolerant insulin-sensitive individuals. Fasting proinsulin concentrations were also higher (P < 0.002) in the normal glucose-tolerant insulin-resistant (15.1 +/- 1.5 pmol/L) and IGT (15.8 +/- 1.8 pmol/L) groups compared to those in normal glucose-tolerant insulin-sensitive volunteers (9.3 +/- 1.2 pmol/ L). However, the ratio of fasting proinsulin to insulin was identical in all three groups (0.12). When the three groups were combined, significant relationships (P < 0.001) existed between SSPG (degree of insulin resistance) and both fasting proinsulin (r = 0.59) and insulin (r = 0.66) concentrations, but not with the ratio of proinsulin to insulin (r = 0.03). These results demonstrate that fasting proinsulin and insulin concentrations are increased in insulin-resistant, nondiabetic subjects, and the more insulin resistant, the greater the increase. In contrast, the ratio of proinsulin to insulin did not vary as a function of insulin resistance. Thus, neither insulin resistance nor the need to secrete more insulin to maintain glucose tolerance necessarily leads to abnormal insulin processing by the beta-cell.