BACKGROUND: Increased secretion of proinsulin has been associated with beta-cell dysfunction. Hyper-proinsulinemia is suggested to be a predictor for the progression of IGT to type 2 DM. In this study, we compared the concentration of insulin, C-peptide and proinsulin levels among the control group, IGT and type 2 DM group during the oral glucose tolerance test. We investigated whether hyperproinsulinemia was an effective predictor of beta-cell impairment befre the clinical onset of type 2 diabetic subjects. METHODS: We studied proinsulin, insulin(using an assay that display appreciable cross-reactivity with proinsulin) and proinsulin:insulin ratio during the oral glucose tolerance test in 14 controls, 20 IGT and 20 type 2 DM. We also compared proinsulin, proinsulin response areas and proinsulin:insulin ratio among the three groups. RESULTS: There were no significant differences in the baseline and 30min proinsulin levels among three groups. However, proinsulin response areas in IGT were higher than those in other groups. Baseline proinsulin/insulin ratio and post-load proinsulin/ insulin ratio were not significantly different among the three groups. In IGT group, the proinsulin response after glucose loading was rapidly increased, but was blunted in diabetic patients. CONCLUSION: We suggest that pancreatic beta cell dysfunction was ongoing before the clinical onset of DM and hyperproinsulinemia, especially the proinsulin response areas during oral GTT may be a predictor for the development of type 2 DM.