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Background: Impaired b-cell function and insulin resistance play etiological role in NIDDM. Removal of glucose toxicity with restoration of blood glucose levels via various modes of therapy has been reported to improve pancreatic b-cell function. The aim of the present study was to evaluate the effect of glucose control on insulin secretion and whether insulin secretion decreases with the duration of the disease. We also evaluated whether C-peptide levels are useful in the selection of treatment modality. Method: The fasting C-peptiide (FCP) and postpandial 2 hour C-peptide (PPCP) were measured before and after insulin treatment in 20 uncontrolled NIDDM patients (group I), among whom the followed-up C-peptide measurement was repeated in 11 patients about 2 years later. In another 46 NIDDM patients (group II), we measured FCP and PPCP during the hyperglycemic period and then examined relationships between FCP and PPCP levels and clinical eharacteristics including mode of therapy about 2 years later. Resalts: 1) In group I patients, mean FCP (0.55+0.35 vs. 0.53+ 0.22 nmol/L respectively) and PPCP (0.79+0.55 vs. 0.80+ 0.33 nmol/L respectively) was not changed by the short term insulin treatment. Divided into two subgroups according to fating blood sugar levels before insulin treatment, mean FPCP of controlled period (1.12+0. 42 vs. 0.71+0.30 nmol/L respectively, p<0.05) was higher in patients with modest fasting hyperglycemia (<10.0mmol/L, n=6) than those with severe fasting hyperglycemia (>11.1mmol/L, n=14). 2) FCP (0,61+0.38 nmol/L) and PPCP (0.92+0.58 nmol/L) were measured again in 11 of group I patients, showing no difference in the C-peptide levels before and after the short term and long term treatment. 3) In group II patients being received long term follow up, the initial clinical eharacteristics including C-peptide levels were not different between patients treated with sulfonylurea and those with insulin at follow up period. Conelusion: The blood sugar levels before the short term insulin treatment may influence the postprandial C-peptide response after control of blood sugar. And, postprandial C-peptide response in NIDDM patients seems not to predict the lang term treatment modality.