Long-term effects of ipragliflozin and pioglitazone on metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes: 5 year observational follow-up of a randomized, 24 week, active-controlled trial: Effect of ipragliflozin in MASLD.

AIMS/INTRODUCTION: We conducted a 5 year post-trial monitoring study of our previous randomized 24 week, open-label, active-controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction-associated steatotic liver disease (MASLD), identical to those of pioglitazone. MATERIALS AND METHODS: In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. RESULTS: At 5 years, the mean liver-to-spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (-4.0%, P = 0.0075 and -7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB-4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. CONCLUSIONS: Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years.

A Pregnant Woman with Excess Vasopressinase-Induced Diabetes Insipidus Complicated by Central Diabetes Insipidus like Lymphocytic Infundibulo-Neurohypophysitis.

Background: Gestational diabetes insipidus (DI) is a very rare complication of pregnancy. We present a case of gestational DI combining two different types of DI. Case Presentation. A 39-year-old pregnant woman suddenly presented with thirst, polydipsia, and polyuria after 31 gestation weeks (GWs). Based on laboratory findings of hypotonic urine (78 mOsm/kgH2O) with higher plasma osmolality (298 mOsm/kgH2O) and higher serum sodium levels (149 mEq/L), gestational DI was suspected, and the clinical course was monitored without therapy until the results of a measurement of plasma arginine vasopressin (AVP) levels were available. However, she subsequently developed acute prerenal failure and underwent an emergency cesarean section at 34 GWs. Her resected placenta weighed 920 g, nearly twice the normal weight. Immediately following delivery, intranasal 1-desamino-8-D-arginine vasopressin was administered, and her symptoms promptly disappeared. Afterward, her predelivery plasma AVP level was found to have been inappropriately low (0.7 pg/mL) given her serum sodium level. The patient's serum vasopressinase level just before delivery was 2,855 ng/mL, more than 1,000 times the upper limit of the normal range, suggesting excess vasopressinase-induced DI. The presence of anti-rabphilin-3A antibodies in the patient's blood, a hypertonic saline infusion test result, and loss of the high-intensity signal of the posterior pituitary on fat-suppressed T1-weighted magnetic resonance images without thickening of the stalk and enlargement of the neurohypophysis suggested concurrent central DI-like lymphocytic infundibulo-neurohypophysitis (LINH). Conclusion: In addition to the degradation of AVP by excess placental vasopressinase due to the enlarged placenta, an insufficient compensatory increase in AVP secretion from the posterior pituitary gland due to LINH-like pathogenesis might have led to DI symptoms.

HLA typing of patients who developed subacute thyroiditis and Graves' disease after SARS-CoV-2 vaccination: a case report.

BACKGROUND: Cases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT. CASE PRESENTATION: We conducted HLA typing of one patient with SAT and another with both SAT and Graves' disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms. CONCLUSION: HLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.

HbA1c level may be a risk factor for oxygen therapy requirement in patients with coronavirus disease 2019.

INTRODUCTION: Many clinical studies have identified significant predictors or risk factors for the severity or mortality of coronavirus disease 2019 (COVID-19) cases. However, there are very limited reports on the risk factors for requiring oxygen therapy during hospitalization. In particular, we sought to investigate whether plasma glucose and HbA1c levels could be risk factors for oxygen therapy requirement. MATERIALS AND METHODS: A single-center, retrospective study was conducted of 131 COVID-19 patients hospitalized at Saitama Medical University Hospital between March 2020 and November 2020. To identify the risk factors for oxygen therapy requirement during hospitalization, a stepwise multivariate binary logistic regression analysis was performed using several clinical parameters commonly obtained on admission, including plasma glucose and HbA1c levels. RESULTS: Of the 131 patients with COVID-19, 33.6% (44/131) received oxygen therapy during hospitalization. According to the logistic regression analysis, male sex (odds ratio [OR]: 8.76, 95% confidence interval [CI]: 1.65-46.5, P < 0.05), age (OR: 1.07, 95% CI: 1.02-1.12, P < 0.01), HbA1c levels (OR: 1.94, 95% CI: 1.09-3.44, P < 0.05), and serum C-reactive protein (CRP) levels (OR: 2.22, 95% CI: 1.54-3.20, P < 0.01) emerged as independent variables associated with oxygen therapy requirement during hospitalization. CONCLUSIONS: In addition to male sex, age, and serum CRP levels, HbA1c levels on admission may serve as a risk factor for oxygen therapy requirement during the clinical course of COVID-19, irrespective of diabetes history and status. This may contribute to the efficient delegation of limited numbers of hospital beds to patients at risk for oxygen therapy requirement.