Background: Insulin secretory defect and insulin resistance are two main etiologic factors of noninsulin dependent diabetes mellitus (NIDDM). However, factors and precise mechanisms of insulin secretory defect in NIDDM are not fully understood. Studies in vivo and in vitro indicated that islet function become impaired as hypergiycemia is maintained chronically. This study examined whether the severity of hyperglycemia influences insulin secretory capacy in NIDDM. Method: Oral glucose tolerance test and glucagon st.imulation test were performed in 46 NIDDM patient. With varymg degree of obesiity and fasting plasma glucose level. To investigate the effect of glucose con trol on insuin secretion, these test were repeated in ten patients who received insulin treatment for 7 to 14 days. C-peptide response was clefined as the difference of peak plasma C-peptide level and basal plasma C-peptide level. :Results: 1) Basal pasma C-petpde level was higher in obese group than in nonobese group anci was welt correlated with body mass index (BMI). There was no significant difference in basal C-peptide levels in patients with different fasting plasma glucose (FPG) levels when the effect of the obesity was correeted No significant changes in basal C-peptie levels were seen after insulin treatment. 2) C-peptide response of oral glucose was significantly less in higher FPG group than in lowr FPG group and was inversely correlated with Fk'G levels. C-peptid responae to oral glucose improved significantly after insulin treatment 3) C-peptide response to glucagon was not different between higher and lower FPG group aru3 was not related with FPG level. C-peptide response ta glucagon dec:veased significantly when near normoglycemia was attained after insulin treatment. Conclusion: Degree of obesity is one of the major factors regulating the basal insulin secretion in NIDDM. C-peptide response to glucose, but not to glucagon, is blte1ted in NIDDM subjects with FPG. Glycemic control ;rfter insulin treatment improved insulin secretory response to glucose but not to glucagon. These results suggest that 1) hyperglycemia might exert cletriment1 effect on insulin secretion in response to glucose but not to glucagon, and that 2) hyperglycemia might potentiate insulin secretory response to non-glucose stirnuli thus contrihute to apparently normal insulir secretory capacity in NIDDM.