Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis.

Non-alcoholic fatty liver disease (NAFLD) is an important common comorbidity in individuals with type 2 diabetes (T2DM). Although some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on NAFLD, the efficacy of once-weekly semaglutide has not been established. This was a subanalysis of the SWITCH-SEMA 1 study, a multicenter, prospective, randomized, parallel-group trial comparing switching from liraglutide or dulaglutide to once-weekly semaglutide in subjects with T2DM (SWITCH) versus continuing current GLP-1RAs (Continue) for 24 weeks. This subanalysis consisted of participants who were suspected to have NAFLD [fatty liver index (FLI) ≥ 30]. In total, 58 participants met the criteria of this subanalysis. There were no statistical differences in baseline characteristics between the SWITCH (n = 31) and Continue groups (n = 27). FLI significantly improved during treatment in the SWITCH group (68.6 to 62.7) but not in the Continue group (71.1 to 72.3) (p < 0.01). The improvement of FLI in the SWITCH group was greater in switching from dulaglutide to semaglutide and significantly correlated with older age (p = 0.016) and lower baseline FLI (p < 0.01). The multiple linear regression analysis revealed that the switch from dulaglutide was associated with an improvement in FLI (p = 0.041). Switching from conventional GLP-1RAs to once-weekly semaglutide might be beneficial for individuals with NAFLD complicated with T2DM.

Metagenomic analysis of ready biodegradability tests to ascertain the relationship between microbiota and the biodegradability of test chemicals.

Ready biodegradability tests conducted in accordance with the Organisation for Economic Co-operation and Development guidelines (test 301C or test 301F) are performed using activated sludge (AS) prepared by the Chemicals Evaluation and Research Institute (AS-CERI) or that taken from a sewage treatment plant (AS-STP). It had been reported that AS-CERI had lower activity than AS-STP in biodegrading test chemicals, and that biodegradation was accelerated by increasing the volume of the test medium. However, these phenomena have not been clarified from the perspective of the microbiota. In this study, using metagenomic analysis, we first showed that the microbiota of AS-CERI was biased in its distribution of phyla, less diverse, and had greater lot-to-lot variability than that of AS-STP. Second, after cultivation for a long period of time, the microbiota of AS-STP and AS-CERI became more similar to each other in terms of community structure. Third, determining degraders of test substances when each substance was actively biodegraded was found to be an effective approach. Finally, we clarified experimentally that a large volume of test medium increased the number of species that could degrade test substances in the condition where the initial concentrations of each substance and AS-STP were kept constant.

Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study).

AIM: To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycaemic control and treatment satisfaction in patients with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-labelled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mg/day (plan A) or dulaglutide 0.75 mg/week (plan B) were either switched to semaglutide or continued current therapy. The primary endpoint was the mean change in glycated haemoglobin over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire scores, body weight and metabolic indices. RESULTS: In total, 110 patients were enrolled, and 10 were excluded; therefore, 37 patients in plan A and 63 patients in plan B completed the study. Glycated haemoglobin levels were significantly reduced in the semaglutide group in both plans [plan A, 7.8% ± 1.0% to 7.8% ± 0.7% (liraglutide) vs. 7.9% ± 0.7% to 7.3% ± 0.7% (semaglutide), p < .01; plan B, 7.8% ± 1.0% to 7.9% ± 1.2% (dulaglutide) vs. 7.8% ± 0.8% to 7.1% ± 0.6% (semaglutide), p < .01]. Semaglutide also improved Diabetes Treatment Satisfaction Questionnaire scores in both groups (plan A, +0.1 vs. +8.3, p < .01; plan B, -1.2 vs. +3.5, p < .01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters. CONCLUSIONS: Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment.

Impact of Glucose Loading on Variations in CD4+ and CD8+ T Cells in Japanese Participants with or without Type 2 Diabetes.

OBJECTIVE: The aim of this study was to examine the fluctuations in CD4+ T cells, CD8+ T cells, and natural CD4+CD25+FoxP3+T-regulatory (Treg) cells following an oral glucose tolerance test (OGTT) in participants with and those without type 2 diabetes (T2DM). METHODS: 19 Japanese participants with T2DM (DM group) and 21 participants without diabetes (non-DM group) were recruited and underwent a 75-g OGTT. The cell numbers of leukocytes, lymphocytes, and the T cell compartment, such as CD4+, CD8+, and Treg, were calculated for blood samples obtained after an overnight 12 h fast and during a 75-g OGTT at 60 and 120 min. RESULTS: Before glucose loading, no differences in the cell numbers of leukocytes, lymphocytes, CD4+, CD8+, and Treg were observed between the DM group and the non-DM group. The proportion of CD8+ was significantly reduced, whereas the proportion of CD4+ was significantly increased, after 120 min of glucose loading in both groups. The proportion of Treg was not affected. Furthermore, a significant positive correlation was observed between the AUC0-120 min of CD8+ and the change in the free fatty acid level following the OGTT (ρ = 0.39, P < 0.05), but not that of glucose or insulin. CONCLUSION: The proportion of CD4+ T cells was increased and that of CD8+ T cells was reduced after glucose loading in both subjects with and without diabetes. These findings suggest that glucose loading dynamically affects the balance of the circulating T lymphocyte subset, regardless of glucose tolerance.

Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus.

The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.

Propagation of the change in the membrane potential using a biocell-model.

A new model system of nerve conduction, which has two sites (the potential-sending and the potential-receiving sites) was constructed by the use of some liquid-membrane cells which mimic the function of the K(+) and Na(+) channels. The model system setup was such that the membrane potential of the K(+)-channel cell (resting potential) was different from that of the Na(+)-channel cell (action potential). Initially, the K(+)-channel cell at the potential-sending site was connected to that at the potential-receiving site. After switching from the K(+)-channel cell to the Na(+)-channel cell at the potential-sending site, the membrane potential of the K(+)-channel cell at the potential-receiving site began to vary with the generation of the circulating current. By placing several K(+)-channel cells in parallel at the potential-receiving site, the propagation mechanism of the action potential was interpreted and the influence of the resistor and the capacitor on the propagation was evaluated.

Usefulness of the octreotide test in Japanese patients for predicting the presence/absence of somatostatin receptor 2 expression in insulinomas.

We investigated the relationship between the results of the octreotide test and somatostatin receptor (SSTR) 2 expression in insulinoma patients, to evaluate the usefulness of this test for predicting SSTR2 expression in insulinomas in Japanese patients. Five females and one male were included in the study. All patients underwent the octreotide test before the surgery carried out to resect the tumor, and histopathological examination of the resected tumor was performed by a single experienced pathologist. SSTR2 expression was evaluated by the SSTR2 immunohistochemistry scoring system. Insulinoma was clinically diagnosed and surgically resected in all six patients. In the octreotide test, suppression of insulin secretion was sufficient after loading in patients 1-4 and 6. In patient 5, however, the suppression of insulin secretion was insufficient, which resulted in severe hypoglycemia with endogenous relative hyperinsulinemia after the octreotide loading. The histopathological findings revealed SSTR2 expression in the insulinomas of patients 1-4 and 6, but not in the insulinoma of patient 5. In conclusion, improvement of hyperinsulinemic hypoglycemia by octreotide in Japanese insulinoma patients was associated with SSTR2 expression in the tumor. Our results suggest that the octreotide test could be useful for predicting SSTR2 expression in the tumor.

Influence of the Circulating Current on the Propagation of the Change in Membrane Potential.

The propagation of the change in potential differences across liquid membranes from the potential-sending cell to the potential-receiving cell was investigated by use of a system combined with three liquid membrane cells, which were composed of two aqueous phases and a 1,2-dichloroethane solution phase. The ionic composition of one potential-sending cell (S) was identical to that of the receiving cell (Rec), and that of another potential-sending cell (Ap) was different from that of the Rec. When the connection of cell Rec was switched from cell S to cell Ap, the change in the membrane potential was caused by the circulating current. The greater the ratio of the interfacial area of the membrane of cell Ap to that of cell Rec, the faster the change in the membrane potential propagated from cell Ap to cell Rec.