Effects of Vildagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on the Parameters of Glucose Metabolism and the Cardio-Ankle Vascular Index in Individuals with Type 2 Diabetes.

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-ß (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m2). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.

Once-weekly semaglutide administered after laparoscopic sleeve gastrectomy: Effects on body weight, glycemic control, and measured nutritional metrics in Japanese patients having both obesity and type 2 diabetes.

Background: Glucagon-like peptide (GLP)-1 analogue may be useful for controlling weight recurrence and diabetes relapse after bariatric surgery, but may also adversely affect the measured nutritional metrics. This study aimed to investigate the effect of treatment with once-weekly semaglutide after laparoscopic sleeve gastrectomy (LSG) in patients with type 2 diabetes (T2D). We also examined the effects of combined use with a low-energy, high-protein formula diet (FD). Methods: This study was a single-center retrospective database analysis. We enrolled 29 Japanese patients with T2D who underwent LSG, and more than 12 months later received semaglutide. The patients were divided retrospectively into a FD group (=6) and a conventional diet (CD) group (n = 23). Results: BMI and HbA1c decreased significantly by 10.7 kg/m2 and 1.1 %, respectively, 12 months after LSG, and decreased by an additional 1.6 kg/m2 and 0.6 % after 12-months of treatment with semaglutide. Decreases in serum albumin, vitamin B12 and zinc were observed only after semaglutide administration. A ratio of energy from protein, fat and carbohydrates changed from 13:31:56 before to 19:30:50 after LSG, and from 17:32:51 before to 15:29:56 after semaglutide. Skeletal muscle ratio, which is the ratio of skeletal muscle mass to body weight, increased after LSG, but did not change after semaglutide. FD group showed a significant increase in skeletal muscle mass per 1 % body weight compared to CD group during semaglutide treatment. Conclusion: Semaglutide after LSG in patients with obesity and T2D resulted in additional weight reduction and improved glycemic control, but worsened measured nutritional metrics. Administration of a low-energy, high protein formula diet may ameliorate adverse nutritional effects of semaglutide in patients with T2D after LSG. (Ethics Committee of Toho University Sakura Medical Center approval number S18061).

Case report: Impact of hyperthyroidism on psychotic symptoms in schizophrenia comorbid with Graves' disease.

Introduction: Auditory hallucinations are the most common type of hallucinations observed in schizophrenia; however, visual hallucinations are not uncommon. In Graves' disease, depression, hypomania, and psychosis can occur. While the association between Graves' disease and psychosis has been explored, understanding of the specific impact of thyroid dysfunction severity on psychiatric symptom severity is limited. Here, we present a case report of a patient with schizophrenia comorbid with Graves' disease whose psychotic symptoms were impacted by hyperthyroidism. Case: The patient was a 32-year-old Japanese woman who presented with auditory and visual hallucinations, agitation, and pressured speech. The patient was diagnosed with schizophrenia comorbid with Graves' disease and thyroid storm. The patient's psychotic symptoms were found to be associated with fluctuations in thyroid hormone levels, and visual hallucinations were observed only during thyroid storms. Treatment involved dexamethasone, potassium iodide, bisoprolol fumarate, and methimazole for thyrotoxicosis, and a blonanserin transdermal patch, paliperidone, and paliperidone palmitate for psychotic symptoms. The patient's auditory and visual hallucinations improved with antipsychotic treatment and decreased thyroid hormone levels. Conclusion: This case highlights the importance of monitoring thyroid function in patients with schizophrenia, particularly those with comorbid Graves' disease. The correlation between psychiatric symptoms and thyroid hormone levels was demonstrated on an individual level over time, with symptoms worsening as thyroid hormone levels increased. Additionally, our case suggests that abnormally high thyroid hormone levels may trigger visual hallucinations in individuals with schizophrenia. Further studies are needed to elucidate the underlying mechanisms and potential treatment implications of this association.

A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation.

Summary: A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 µU/mL; 60 min: 953 µU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother's diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years. Learning points: Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance. Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed. Clinical courses may differ even if the same genetic mutation is found in a family.

Coexistence of Pheochromocytoma and Primary Aldosteronism due to Multiple Aldosterone-producing Micronodules in the Ipsilateral Adrenal Gland.

A 46-year-old woman was referred for hypertension and a right adrenal tumor. Primary aldosteronism (PA) was suspected because of the high plasma aldosterone concentration-to-plasma renin activity ratio. However, a subsequent evaluation revealed coexistent PA and pheochromocytoma. We performed laparoscopic right adrenalectomy. Histology of the resected adrenal gland confirmed pheochromocytoma and multiple aldosterone-producing adrenocortical micronodules. Following adrenalectomy, the urinary catecholamine levels normalized, and hyperaldosteronism improved but persisted. Hypertension also improved but persisted and was normalized with spironolactone. The clinical course indicated that the PA lesions were likely bilateral. This was a histologically proven case of coexistent pheochromocytoma and PA due to multiple aldosterone-producing micronodules.

Retained surgical sponge in the thigh: report of the third known case in the limb.

We report a retained surgical sponge (gossypiboma) in the thigh, which mimicked a neoplasm. A 25-year-old man, who had a past history of external fixation for femoral shaft fracture, complained of swelling in the left thigh with pain. A radiograph of the thigh showed periosteal reaction. T1-weighted magnetic resonance (MR) images showed a well-defined mass with heterogenous signal intensity, and T2-weighted images showed tortuous lines of low signal intensity within the mass. Surgical excision revealed a retained gauze sponge within the mass. Histopathological examination revealed foreign body reaction related to the retained gauze sponge. Our case, the third to our knowledge of gossypiboma in a limb, demonstrated characteristic MR imaging findings.

Distribution of type VI collagen in chondrocyte microenvironment: study of chondrons isolated from human normal and degenerative articular cartilage and cultured chondrocytes.

The chondron is the microanatomical unit composed of a chondrocyte and its pericellular microenvironment (PCME), including the pericellular matrix and capsule. In the present study, we extracted chondrons from human articular cartilages and investigated the relationship between the distribution of the matrix molecules, including type VI collagen, and the degeneration of articular cartilage. We also investigated the effects of interleukin-1beta (IL-1beta) and transforming growth factor beta-1 (TGF-beta1) on the distribution of type VI collagen in cultured chondrocytes. Chondrons were extracted by low-speed homogenization from cartilage pieces obtained from forensic autopsies and from patients with knee osteoarthritis (OA) undergoing total knee arthroplasty. Cartilage sections were classified into three groups (normal, slight degeneration, and moderate degeneration) based on the degree of degeneration according to Mankin's score. Extracted chondrons were immunostained, and the distribution of the matrix molecules, including type VI collagen, was investigated using a confocal laser scanning microscope (CLSM). The chondrocytes isolated by enzymic treatment were subjected to three-dimensional culture in agarose gel and then treated with IL-1beta or TGF-beta1. The distribution of newly synthesized type VI collagen in agarose gel was also investigated using the CLSM. Type VI collagen was localized specifically within the PCME of chondrons. The volume ratio of PCME to chondrocyte (P/C ratio) was significantly higher in the moderate degeneration group than in the other two groups. The accumulation of type VI collagen around a chondrocyte was obviously increased by the addition of TGF-beta1. The P/C ratio significantly increased as the severity of the OA progressed, suggesting that type VI collagen distributed specifically in the PCME was playing a protective role for chondrocytes by maintaining the pericellular microenvironment in OA.