BACKGROUND: To evaluate the relationships between deterioration in insulin secretion and aggravated insulin resistance in patients with newly diagnosed prediabetes (preDM) and type 2 diabetes mellitus (T2DM) according to the presence of metabolic syndrome (MS). METHODS: We performed oral glucose tolerance test (OGTT) on 322 drug naive subjects with a history of hyperglycemia of < or = 3 months, and divided these patients into 3 groups, normal glucose tolerance (NGT), preDM (IFG and/or IGT) and T2DM. We also diagnosed these subjects with respect to MS according to ATP III criteria modified by Asia-Pacific guidelines and compared IGI and HOMA-IR in the 3 groups. RESULTS: According to OGTT, 63 subjects were diagnosed with NGT, 81 with preDM, and 178 with T2DM. Using modified ATP III criteria, 218 (67.7%) subjects were diagnosed as MS. When compare groups stratified by the presence of MS, preDM and T2DM groups with MS showed significantly higher mean HOMA-IR and IGI than those without MS. When compare groups with respect to glucose tolerance, NGT, preDM, and T2DM subgroups in MS group showed significant higher HOMA-IR and lower IGI according to glucose tolerance. However, NGT, preDM, and T2DM subgroups in non-MS group showed a significant decrease in IGI but no significant difference in HOMA-IR as glucose tolerance worsened. CONCLUSION: Deterioration in IGI and aggravation of HOMA-IR are both important in the primary pathogenesis of diabetes in those with MS. However, IGI deterioration may be the only important factor in the primary pathogenesis of T2DM in the absence of MS.