PLASMA-INSULIN, C-PEPTIDE, AND PROINSULIN CONCENTRATIONS IN OBESE ANDNONOBESE INDIVIDUALS WITH VARYING DEGREES OF GLUCOSE-TOLERANCE

Conventional immunoassays to quantify insulin concentration do not dif ferentiate between insulin and proinsulin. Thus, previous conclusions as to the relationship between the development of hyperglycemia in pat ients with noninsulin-dependent diabetes mellitus (NIDDM) and pancreat ic insulin secretory function may have been confounded by not being ab le to determine the contribution made by plasma proinsulin to the puta tive measurements of plasma insulin concentration in these patients. T he current study was initiated to address this issue by making specifi c measurements of plasma insulin, proinsulin, and C-peptide concentrat ions in 42 individuals: 14 with normal glucose tolerance, 12 with impa ired glucose tolerance (IGT), and 16 with NIDDM. The study population was further subdivided into a nonobese (body mass index, <30 kg/m2) an d an obese (body mass index, >30 kg/m2) group. Mixed meals were given at 0800, 1200, and 1800 h, and blood was removed at 0800 h (before the meal) and at hourly intervals from then until 1600 h. Plasma glucose concentrations throughout the sampling period were slightly, but signi ficantly (P < 0.01), greater in patients with IGT than in normal indiv iduals. Patients with NIDDM had markedly elevated glycemic excursions, greater than either of the other two groups (P < 0.002). Both plasma immunoreactive insulin and C-peptide concentrations from 0800-1600 h w ere higher (P < 0.002-0.001) in patients with either IGT or NIDDM than in the group with normal glucose tolerance. Although day-long plasma immunoreactive insulin and C-peptide concentrations were higher, on th e average, in patients with IGT compared to those with NIDDM, the diff erence was not statistically significant. Plasma proinsulin concentrat ions were highest in patients with NIDDM (P < 0.002), lower in those w ith normal glucose tolerance (P < 0.002), and intermediate in patients with IGT. When the calculated ''true' insulin concentration was deter mined by taking the proinsulin content into consideration, patients wi th IGT had the highest day-long levels, with the lowest values found i n the control population (P < 0.002). Although absolute values varied as a function of obesity, the generalizations outlined above were foun d in both weight groups. These results show that ambient plasma proins ulin concentrations increase as glucose tolerance declines. However, t rue plasma insulin concentrations in response to mixed meals remain hi ghest in patients with IGT, lowest in normal individuals, and intermed iate in patients with NIDDM. Thus, previous conclusions that absolute day-long plasma insulin concentrations are not lower than normal in pa tients with NIDDM do not appear to result from an inability to differe ntiate true insulin from proinsulin.