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.

Aims/Introduction: Metformin is associated with the risk of gastrointestinal complications, and probiotic Bifidobacterium bifidum G9‐1 (BBG9‐1) can improve the symptoms of diarrhea. This study aimed to clarify the effects of probiotic BBG9‐1 on the gastrointestinal symptoms of type 2 diabetes mellitus patients using metformin.Materials and methods: In this open‐label single‐arm exploratory study, 40 patients (mean age 64.0 ± 9.4 years) were given probiotic BBG9‐1 for 10 weeks. Changes in the gastrointestinal symptom rating scale total score, which was the primary end‐point, gastrointestinal symptom rating scale subscale scores, glycated hemoglobin levels and gut microbiota after the administration of probiotic BBG9‐1 were evaluated by the Student's t‐test.Results: The gastrointestinal symptom rating scale total score significantly improved (from 2.02 ± 0.51 to 1.59 ± 0.43, change, −0.43 ± 0.49, P < 0.001). Furthermore, all gastrointestinal symptom rating scale subscale scores, including diarrhea (from 2.32 ± 1.14 to 1.89 ± 0.99, change, −0.42 ± 0.95, P = 0.007) and constipation (from 3.00 ± 1.16 to 2.20 ± 1.07, change, −0.80 ± 1.19, P < 0.001), scores also significantly improved. However, the glycated hemoglobin levels did not change (from 7.0 ± 0.7 to 7.0 ± 0.6%, change, 0.0 ± 0.4, P = 0.91). The relative abundance of the genus Sutterella decreased by the use of probiotic BBG9‐1 (from 0.011 ± 0.009 to 0.008 ± 0.006, change, −0.003 ± 0.006, P = 0.002).Conclusions: Type 2 diabetes mellitus patients treated with metformin showed significant improvement in all gastrointestinal symptom rating scores after using probiotic BBG9‐1 without changing the glucose control. This study showed the potential usefulness of probiotic BBG9‐1 for improving gastrointestinal symptoms, including constipation and diarrhea, in type 2 diabetes mellitus patients treated with metformin.

Recently, the genetic background of pheochromocytomas/paragangliomas (PPGLs) has been rapidly revealed. These tumors have been referred to as the “ten percent tumor”; however, the frequency of genetic variants of PPGLs has turned out to be more common than expected. PPGLs are potentially hereditary tumors and appear clinically sporadic. Here, we report a case of bilateral pheochromocytoma (PCC) with a variant in the MYC-associated factor X (MAX) gene (c.295 + 1G > A). A male patient was diagnosed with adrenal pheochromocytoma (PCC) and underwent a left adrenalectomy at the age of 40. A new tumor in the right adrenal gland was detected at the age of 43. Urinary metanephrine and normetanephrine concentrations gradually increased. The size of the right adrenal PCC continued to increase one year after detection. Genetic testing of the peripheral blood revealed the presence of a pathogenic variant in MAX. The natural history of adrenal PCCs with the MAX variant has not yet been clarified, because the number of reported cases is not sufficient. Thus, clinicians should consider a MAX variant when they find bilateral or multiple PCCs.

Primary hyperparathyroidism (pHPT) during pregnancy is a rare but clinically significant condition associated with severe maternal and fetal complications. Diagnosis and management are challenging owing to symptoms overlapping with pregnancy-related conditions. A 28-year-old woman at 6 weeks of gestation presented with severe hypercalcemia (ionized calcium 2.80 mmol/L) (reference range, 1.15-1.29 mmol/L) leading to acute respiratory distress syndrome (ARDS), renal failure, and fetal demise. Despite initial management with hemodialysis and veno-venous extracorporeal membrane oxygenation (V-V ECMO), hypercalcemia and impaired respiratory status persisted until a parathyroid nodule was resected surgically. Postoperatively, calcium levels normalized, and the patient was successfully weaned off V-V ECMO; however, chronic kidney disease persisted. This case highlights the systemic effects of severe hypercalcemia in pregnancy, including ARDS and nephrocalcinosis. The case underscores the importance of a timely diagnosis and surgical intervention, as well as the need for a multidisciplinary approach to optimize outcomes in complex cases of pHPT during pregnancy. This report emphasizes the critical role of early recognition and management of pHPT during pregnancy to mitigate severe complications. Future research should focus on improving diagnostic strategies and refining treatment protocols for complex cases involving hypercalcemia-induced multiorgan dysfunction.