BACKGROUND: Type 2 diabetes mellitus is characterized beta cell dysfunction and insulin resistance but the relative roles of the two factors are different in various ethnic groups. The changes in plasma proinsulin levels is thought to be a marker for the beta-cell dysfunction. To study the role of beta cell dysfunction in the pathogenesis of type 2 diabetes mellitus we compared the concentrations of plasma insulin, C-peptide and proinsulin among the control group, impaired glucose tolerance (IGT) group and newly diagnosed Type 2 Diabetes Mellitus (DM) group during the oral glucose tolerance test. METHODS: In 47 newly diagnosed patients with type 2 DM, 9 IGT and 13 controls the 75g oral glucose tolerance test (OGTT) were performed and samples were analyzed for glucose, insulin, C-peptide and proinsulin. RESULTS: 1) In IGT group plasma insulin, C-peptide and proinsulin concentrations were increased markedly during OGTT but were blunted in type 2 diabetes group. 2) The basal plasma proinsulin level was 7.7+/-4.4 pmol/L in control group, 15.2+/-6.9 pmol/L (p<0.005) in IGT group, and 16.9+/-8.3 pmol/L (p<0.005) in type 2 DM group, and the proinsulin levels at 60 min, 90 min, 120 min during OGTT were significantly elevated in IGT group than those of control group. 3) The plasma proinsulin/insulin ratio were significantly increased in IGT group and type 2 DM group at basal and 30 min during OGTT. 4) The proinsulin response areas were significantly increased in IGT group (110.7+/- 13.1 pmol/L/hr, p=0.048) than those of control group (73.6+/-5.1 pmo l/L/hr) and type 2 DM group (80.5+/-5.9 pmol/L/hr). CONCLUSION: Beta cell secretory defects such as proinsulin secretion were present in impaired glucose tolerance and the changes of insulin secretory function might have a role in the pathogenesis of type 2 DM.