Basal circulating concentrations of islet B cell products were measured using two-site monoclonal antibody-based immunoradiometric assays after a 10 h overnight fast in a group of non-obese subjects with recently diagnosed impaired glucose tolerance (World Health Organization criteria). A group of healthy subjects with normal oral glucose tolerance matched for age and body mass index served as normal controls. 2. Fasting blood glucose concentration was normal in all subjects with mean (+/- SEM) levels of 5.1 +/- 0.2 and 4.8 +/- 0.2 mmol/l (P > 0.1) for the group with impaired glucose tolerance and the healthy control group, respectively. 3. There was no significant difference (P > 0.1) in fasting plasma insulin or C-peptide concentrations between the groups. 4. By contrast, the fasting concentration of intact proinsulin was nearly four-fold higher in the subjects with impaired glucose tolerance than in the matched healthy control subjects (4.5 +/- 1.0 versus 1.2 +/- 0.2 pmol/l, P < 0.005). 5. Similarly, the fasting plasma concentration of 32-33 split proinsulin in the subjects with impaired glucose tolerance was almost twice that of the control subjects (7.4 +/- 1.3 versus 3.9 +/- 0.8 pmol/l, P < 0.02). 6. In conclusion, fasting concentrations of proinsulin-like molecules are elevated in non-obese subjects with newly diagnosed impaired glucose tolerance. This observation is consistent with defective islet B cell proinsulin processing in this syndrome.
