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Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H2S) levels in patients with type 2 diabetes, as the plasma H2S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H2S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H2S levels were measured using the methylene blue assay. The plasma H2S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H2S levels (45.1±15.5 μM versus 54.0±26.4 μM, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H2S levels and the HbA1c levels (β=-0.505, p<0.01), Furthermore, a reduction in the plasma H2S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.9±13.8 μM versus 47.5±15.9 μM, p<0.01). Conclusion Collectively, the plasma H2S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549).

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IntroductionThe efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM).MethodsThe subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180, <70 mg h/dL) after the start of administration were compared with the pretreatment values. In addition, we compared changes in the number of insulin units between basal and bolus insulin. Furthermore, we investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-2′-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and adiponectin as parameters.ResultsThe mean glucose concentrations decreased from 161.1 to 139.1 mg/dL (P < 0.01). The SD decreased from 36.5 to 29.6 mg/dL (P = 0.05). The MAGE decreased from 89.2 to 77.4 mg/dL (P < 0.01), and the MODD decreased from 34.3 to 25.5 mg/dL (P < 0.05). All parameters showed significant improvements in diurnal changes. AUC of ≥180, i.e., the total area of blood glucose levels at or above 180 on the blood glucose curve of CGM, decreased from 339.1 to 113.6 mg/dL (P < 0.05). AUC of <70, i.e., the total area of blood glucose levels below 70 on the blood glucose curve of CGM, slightly decreased from 1.6 to 0.3 mg/dL (P = 0.08). The total number of basal insulin units decreased from 128 to 76, and that of bolus insulin decreased from 266 to 154; the dose of insulin could be markedly decreased. In addition, the mean 8-OHdG level decreased from 11.4 to 10.8 ng/mg Cre (P < 0.05), and the mean TNF-α level decreased from 2.31 to 1.79 pg/mL (P = 0.10). The mean adiponectin level increased from 5.01 to 5.53 μg/mL (P < 0.05).ConclusionCanagliflozin improved blood glucose changes in type 2 diabetes using insulin. In addition, the results suggest its antioxidant actions.Trial RegistrationUniversity Hospital Medical Information Network (UMIN no. 000019429).

BackgroundThe aim of the present study was to elucidate the effect of teneligliptin on oxidative stress and endothelial function in Japanese patients with type 2 diabetes and chronic kidney disease (CKD).MethodsForty-five patients with type 2 diabetes and CKD who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) for 24 weeks. The following parameters were evaluated at baseline and after 24 weeks of treatment with continued sitagliptin or teneligliptin: blood pressure, haemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), urinary albumin excretion, endothelial function by reactive hyperaemia index (RHI; EndoPAT® system), reactive oxygen metabolites (ROMs) measured by the d-ROMS test, 8-hydroxy-2′-deoxyguanosine, urinary liver-type fatty acid binding protein (L-FABP), and urinary 8-isoprostane.ResultsThe two groups did not significantly differ with regard to age, male-to-female ratio, duration of diabetes, body mass index, HbA1c, eGFR, or urinary albumin excretion levels at baseline. We found no significant differences in changes of HbA1c, eGFR, or urinary albumin excretion levels between the two groups after 24 weeks of treatment. However, treatment with teneligliptin, but not sitagliptin, significantly improved RHI values and was correlated with the percent changes in RHI and d-ROMs.ConclusionsThe present study demonstrated that teneligliptin, can improve endothelial function and reduce renal and vascular oxidative stress in patients with type 2 diabetes and CKD, independently of reducing albuminuria or improving glucose control.Trial registration UMIN000017180