Non-obese diabetic mice aged 30 to 60 days were treated orally with Cyclosporin at doses of 25, 15 and 2.5 mg/kg every 2 days until 160 days of age. Diabetes developed in 12 out of 18 oil-treated mice (67%), with partial to complete Langerhans' islet destruction associated with lymphocytic infiltration. The non-obese diabetic mice showed a plasma glucose concentration of 6.62 +/- 0.92 mmol/l (mean +/- SD) at 50 days of age. The plasma glucose level of oil-treated non-obese diabetic mice gradually increased after 130 days of age and reached 14.0 to 19.0 mmol/l at 160 days of age, while Cyclosporin-treated non-obese diabetic mice showed neither clear increase of plasma glucose levels nor development of insulitis. The cumulative incidence of diabetes in Cyclosporin-treated mice was significantly lower than that in oil-treated mice (p less than 0.01). Subsequently, Cyclosporin treatment was started after development of glucose intolerance. Twenty-five mg/kg of Cyclosporin was administered every 2 days for 35 days. Cyclosporin appeared to have little therapeutic effect on diabetes in non-obese diabetic mice.

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Aims/IntroductionWe carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics.Materials and MethodsWe analyzed the CoDiC® database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug‐naïve patients who were initiated with metformin, dipeptidyl peptidase‐4 inhibitor (DPP‐4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors.ResultsHbA1c was reduced with all drugs, with the largest effect elicited by DPP‐4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age‐of‐onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00).ConclusionsThe effect on bodyweight and glycemic control differed among metformin, DPP‐4i and SU, and the difference was associated with clinical features.

Sera containing islet cell surface antibodies show a complement-dependent cytotoxic reaction against islet cells, but it has not yet been clarified whether islet cell surface antibodies exhibit cell-mediated cytotoxicity to these cells. By 51Cr release assay we investigated whether islet cell surface antibodies showed a cytotoxic reaction to human pancreatic B cells (JHPI-1 clone) in the presence of normal human lymphocytes. The sera from 14 islet cell surface antibody-positive, 16 islet cell surface antibody-negative Type 1 (insulin-dependent) diabetic patients and 18 islet cell surface antibody-negative healthy subjects were studied. Four sera containing islet cell surface antibodies showed specific cytotoxicity above the mean +3SD value of healthy subjects, and the mean specific cytotoxicity of islet cell surface antibody-positive sera differed significantly from that of both islet cell surface antibody-negative groups. These results suggest that this cell-mediated cytotoxic mechanism may play an important role in the pathogenesis of Type 1 diabetes.