INSULIN DEFICIENCY and insulin resistance are major causes of type 2 diabetes (T2DM) [1]. In particular, delayed and inadequate postprandial insulin secretion is a significant problem for Japanese T2DM patients [2]. We previously analyzed 2,021 Japanese subjects who underwent a 75g oral glucose tolerance test (75g OGTT). We found that the area under the plasma insulin curve (AUC-Ins) of 483 subjects with newly diagnosed diabetes increased along with the increment of fasting plasma glucose (FPG) until it reached the maximum at an FPG of 110 mg/dL, after which AUC-Ins declined as FPG increased further [3]. This result sug- Abstract. The aim of the present study was to evaluate the effect of insulin glargine (Gla) (as part of basal-supported oral therapy) on endogenous insulin secretion and beta-cell function in type 2 diabetic patients. In 33 insulin-naive patients showing poor glycemic control on treatment with sulfonylurea (SU)-based OADs without DPP4 inhibitors, once-daily injection of Gla was added without changing OADs, and the dose of Gla was titrated to attain a fasting plasma glucose (FPG) <110 mg/dL over 24 weeks. Morning meal tests were done at baseline, 12 weeks and 24 weeks. FPG and 2-hour plasma glucose (2HPG) and serum C-peptide (FCPR and 2HCPR) were measured 3 times, while serum intact proinsulin (FPI and 2HPI) was measured at baseline and 24 weeks. Levels of FPG, FCPR, 2HPG, and HbA1c were significantly reduced from baseline at 24 weeks (176±52 to 117±27 mg/dL, p<0.01; 2.0±0.9 to 1.6±1.0 ng/mL, p<0.01; 257±53 to 202±27 mg/dL, p<0.01; and 8.4±0.9 to 7.3±0.6%, p<0.01, Mean±SD), but 2HCPR was unchanged. The patients were divided into two groups depending on whether FPG at 24 weeks was <110 mg/dL or not: attained group (n=15) and not attained group (n=18). The dose of Gla did not differ between the two groups, but the 2HPI/2HCPR ratio at 24 weeks showed a significant decrease from baseline in the attained group. Supplementation with Gla improved glycemic control and maintained intrinsic basal insulin secretion, without changing 2-hour postprandial secretion. Achieving good glycemic control with an FPG<110 mg/dL by adding Gla decreased the 2HPI/2HCPR ratio at 24 weeks.Key words: Type 2 diabetes, Insulin glargine, Proinsulin/C-peptide ratio, Free fatty acids gested that the compensatory increase of postprandial insulin secretion may reach a limit around an FPG of 110 mg/dL in Japanese persons. Thus, it would be interesting to investigate whether the impaired postprandial insulin secretion of patients with poor glycemic control and an FPG>110 mg/dL could recover if FPG was reduced below 110 mg/dL by basal insulin supplementation. Basal insulin combined with oral antidiabetic drugs (OADs) is called basal-supported oral therapy (BOT), and the FPG-lowering effect of BOT in T2DM patients with insufficient control by OADs has been reported previously [4]. Insulin glargine (Gla) is a longacting insulin analog with a sustained profile of action over 24 hours that causes hypoglycemia much less frequently than NPH...