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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. Probiotic Bifidobacterium bifidum G9‐1 (BBG9‐1) improved gastrointestinal symptoms, including diarrhea and constipation, without changing glucose control in type 2 diabetes mellitus patients treated with metformin. The relative abundance of the genus Sutterella decreased by the use of probiotic BBG9‐1.

Background Cushing’s syndrome (CS) during pregnancy is a rare condition associated with significant maternal and fetal complications, including hypertension, diabetes, preeclampsia, and preterm birth. Diabetes insipidus (DI) in pregnancy is a rare but often diagnosed condition, and its effective management is crucial for maintaining maternal health during pregnancy and childbirth. This case report describes the rare coexistence of DI and CS during pregnancy, highlighting the unique complexities in diagnosis and management. Case presentation A 29-year-old woman with a history of pregnancy-induced hypertension developed severe hypertension, hypokalemia, and polyuria (6.6 L/day) during her 7th pregnancy. Laboratory findings showed elevated cortisol, suppressed adrenocorticotropic hormone (ACTH), and a 30-mm left adrenal mass, confirming adrenal CS. Despite potassium supplementation, persistent polyuria and fluid imbalance necessitated initiating desmopressin therapy at 27 weeks of gestation. The patient subsequently developed preeclampsia and underwent emergency cesarean section at 29 weeks, delivering a 1197-g infant with a very low birth weight. Polyuria resolved postpartum, and she underwent left adrenalectomy after discharge. Conclusions This case illustrates the complexity of managing coexisting CS and GDI during pregnancy, emphasizing the importance of considering alternative mechanisms, such as cortisol-induced antidiuretic hormone resistance, in polyuria. Multidisciplinary approaches are crucial to optimizing maternal and fetal outcomes in rare endocrine conditions, and help contribute to the understanding of CS and DI interactions during pregnancy.

Albuminuria is a prognostic marker of worsening renal outcomes in people with hypertension and type 2 diabetes. High home systolic blood pressure is associated with the development of diabetic nephropathy. We assessed the impact of chronic high home blood pressure on diabetic nephropathy progression 10 years after study entry. The participants measured their blood pressure three times in the morning for 14 days at study entry and 10 years after study entry. A retrospective cohort of 165 people with type 2 diabetes at a single hospital was classified into four groups (good control maintenance, improvement, deterioration, and continuous high blood pressure groups) according to a morning home systolic blood pressure ≥125 mmHg at study entry and 10 years after study entry. Logistic regression analysis was performed to determine the association between home blood pressure control and the progression of diabetic nephropathy. After 10 years of entry, the status of nephropathy improved for 5.5% of the participants, remained unchanged for 72.1%, and progressed for 22.4%. The odds ratio of the continuous high blood pressure group versus that of the good control maintenance group for the progression of diabetic nephropathy was 10.41 (95% CI, 1.26-86.15). After adjusting for the introduction of renin-angiotensin-aldosterone system inhibitors during the follow-up period, there was no significant difference in the odds ratio of worsening nephropathy between these groups. The deterioration and improvement groups did not have significant diabetic nephropathy progression compared to the good control maintenance group. Chronic high home blood pressure was associated with the progression of diabetic nephropathy, and RAAS inhibitors could attenuate the negative effect. We demonstrated that chronic home blood pressure was associated with the progression of diabetic nephropathy.

We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow‐up of 7.0 (interquartile range, 4.0–9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02–2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes.

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.

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.

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.

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.