In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

Background: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. Methods: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.

This study reports the use of single-cell RNA sequencing to evaluate B cells in the peripheral blood mononuclear cells (PBMCs) and intrathyroidal blood mononuclear cells of patients with Graves’ disease (GD) undergoing thyroidectomy. These cells were stimulated with overlapping peptides of thyroid autoantigens, including thyroid-stimulating hormone receptor (TSHR), thyroglobulin (Tg), and thyroid peroxidase (TPO). In PBMCs, naive B cells are characterized by IL6 and CXCR5, whereas memory B cells express IGHG1, IGHG2, and CD74. HLA-DMA, HLA-DRB1, IGHG, IGHM, CD74, CD79A, and MS4A1 expression increased in peptide-stimulated naive and memory B cells compared to those in the controls. Thyroid naive B cells are characterized by CD40 and TNFRSF13C, whereas memory B cells express IGHM, CD79A, and MS4A1. Thyroid B cells showed higher DUSP1, DUSP2, CD69, FOSB, RGS1, and immunoglobulin gene expression than control PBMCs and thyroid cells. B-cell receptor analysis revealed frequent IGHV3-23 and IGHV4-34 usage in controls, whereas IGHV4-34/IGHJ4 expression was increased in TSHR-stimulated groups. We concluded that B-cell responses to TSHR, Tg, and TPO differed and that changes in B-cell reactivity also occurred in PBMCs and the thyroid. Additionally, IGHV3-23 and IGHV4-34 may be associated with autoantibody production in GD.

Background: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. Methods: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. Results: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15–4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. Conclusion: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.

Background: Hypertension is present in more than 50% of patients with type 2 diabetes mellitus. Dietary salt restriction is recommended for the management of high blood pressure. Instructions on dietary salt restriction, provided by a dietitian, have been shown to help patients reduce their salt intake. However, appointments for the dietitians in hospitals are often already fully booked, making it difficult for patients to receive instructions on the same day as the outpatient clinic visit. Aim: The aim of this trial is to test a new intervention to assess whether guidance on dietary salt restriction provided by physicians during outpatient visits is effective in reducing salt intake in patients with type 2 diabetes mellitus who have an excessive salt intake. Methods: In this unblinded randomized controlled trial (RCT), a total of 200 patients, male or female, aged between 20 and 90 years, who have type 2 diabetes mellitus and consume excessive salt will be randomly assigned to two groups: an intervention group and a control group. In addition to being given routine treatment, participants in the intervention group will be given individual guidance on restricting their dietary salt intake by a physician upon enrollment. The control group will only be given routine treatment. Participants will be followed up for 24 weeks. The primary outcome will be dietary salt intake, which will be assessed at baseline and at 8, 16, and 24 weeks. The secondary outcomes, including body weight, body mass index, hemoglobin A1c level, blood pressure, blood glucose level, serum lipid profile, and urinary albumin excretion level, will be assessed at baseline and at 8, 16, and 24 weeks. Discussion: The results of this RCT have the potential to provide a simple and novel clinical approach to reduce salt intake among patients with type 2 diabetes, making regular visits to their physician, in outpatient facilities. This protocol will contribute to the literature because it describes a practical intervention that has not been tested previously, and it may serve as guidance to other researchers interested in testing similar interventions. Trial registration: University Hospital Medical Information Network (UMIN), UMIN000028809. Registered retrospectively on 24 August 2017. http://www.umin.ac.jp.