Endocrine journal最新文献

East Asians are known to develop diabetes mellitus at a lower body weight than Caucasians, potentially because of the different mechanisms underlying disease development. This study aimed to evaluate the variation in weight transition leading to diabetes onset in two subtypes of individuals (obese and non-obese) in a Japanese population. We conducted a retrospective, observational, longitudinal cohort study using health checkup data from 9, 260 participants in Japan. Individuals who developed diabetes within three years of the start of the observation period were excluded. Among the participants, 61.4% were men, and 259 developed diabetes. In the obesity group (body mass index [BMI] ≥25 kg/m²), the average BMI increased prior to the diabetes onset and subsequently decreased. Conversely, in the non-obesity group (BMI <25 kg/m²), the average BMI decreased and then stabilized before the onset of diabetes. Notably, a greater number of participants in the non-obesity group exhibited a BMI change of ≤-0.15 kg/m² per year compared with those with a BMI change of ≥0.15 kg/m² per year before diabetes onset (p = 0.003). Our findings indicate that body weight loss precedes the onset of diabetes in the non-obesity group. We recommend that non-obese individuals with elevated blood glucose levels who do not meet the criteria for diabetes should be considered a high-risk group for diabetes development. Therefore, it is imperative to identify these individuals and provide lifestyle guidance that does not focus on weight loss to prevent the onset of diabetes.

The incidence of immune checkpoint inhibitor (ICI)-induced type 1 diabetes mellitus (ICI-T1DM) has increased as the use of ICIs has increased. Autoimmune ICI-T1DM often presents as diabetic ketoacidosis, resulting from insulin deficiency, among which insulin resistance is extremely rare. Here, we describe a patient with advanced myxoid liposarcoma who developed sintilimab-induced fulminant autoimmune diabetes associated with insulin resistance and metabolic disorders. The patient eventually required the combined use of insulin, metformin, liraglutide, and dapagliflozin to reduce blood glucose due to erratic glycaemic excursions and high insulin requirements during his duration of hospital stay. Metformin, dapagliflozin and liraglutide were discontinued because of weight loss half a year after discharge, and intensive insulin therapy was continued. The patient's blood glucose control was poor, and liraglutide and metformin were then added again, half a year later. Together, metformin, dapagliflozin and liraglutide in combination with insulin may help control blood glucose in ICI-induced DM patients with insulin resistance.

Some patients with Graves' disease (GD) develop hypothyroidism after antithyroid drug (ATD) treatment and are found to be positive for thyroid stimulation-blocking antibody (TSBAb). However, thyroid volume (TV) changes throughout this process remain unclear. Therefore, we aimed to quantify TV changes before and after hypothyroidism onset in patients with GD harboring TSBAb and compare them with those in patients with GD who developed hypothyroidism without TSBAb or achieved remission with ATD. This retrospective study evaluated TV changes using ultrasonography in three groups: 10 patients with GD who developed hypothyroidism with TSBAb (TSBAb(+)-hypo group), nine without TSBAb (TSBAb(-)-hypo group), and 91 who achieved remission after ATD treatment (Remission group). In the TSBAb(+)-hypo group, TV significantly decreased from the hyperthyroid to hypothyroid phase (median: 33.3 mL [range: 14.2-52.0] vs. 13.6 mL [4.3-23.3], respectively; p = 0.001). In the TSBAb(-)-hypo group, TV significantly decreased from the hyperthyroid to hypothyroid phase (26.6 mL [11.9-49.2] vs. 20.9 mL [7.4-34.2], respectively; p = 0.037). In the Remission group, TV also decreased significantly from the hyperthyroid to remission phase (29.8 mL [8.2-88.4] vs. 25.1 mL [9.5-72.0], respectively; p = 0.0002). The decrease in TV was significantly higher in the TSBAb(+)-hypo group than in the TSBAb(-)-hypo and Remission groups (53.9% [37.9-74.5] vs. 30.9% [-22.3 to 63.0] and 10.7% [-100.7 to 52.0], respectively; p = 0.027 and <0.0001). This study documents the first precise measurement of TV reduction using ultrasonography in patients with GD who developed hypothyroidism with TSBAb, showing a markedly greater decrease than in those without TSBAb or in remission after ATD treatment.

Somatrogon is a long-acting recombinant human growth hormone approved in several countries, including Japan, for the treatment of children with growth hormone deficiency (GHD). In this study (Clinicaltrials.gov:NCT03874013) Japanese patients with GHD initially received once-weekly somatrogon or once-daily somatropin (0.175 mg/kg/week) for 12 months in the main study period; those who completed the main study were eligible to enroll in a single-arm, 3-year open-label extension (OLE) and receive once-weekly somatrogon (0.66 mg/kg/week). The primary endpoints of the OLE included annualized height velocity (HV), change in height standard deviation score (SDS), and safety. Of 43 patients who completed the main study, 42 continued into the OLE and 40 completed the OLE. Patients were analyzed by treatment received (somatrogon vs. somatropin) during the main study. Mean (SD) HV at OLE baseline was higher in patients originally randomized to somatrogon vs. somatropin (9.78 [1.59] vs. 7.70 [1.10] cm/year); mean HV was similar between original treatment groups for all other OLE timepoints. Mean height SDS increased from main study baseline through the end of the OLE in both treatment groups. During the OLE, 22 (100%) somatrogon-treated patients and 18 (90%) somatropin-treated patients reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild or moderate in severity and no patients discontinued from the OLE or required dose reductions due to TEAEs. Up to 4 years of treatment with once-weekly somatrogon resulted in improved growth response and was well tolerated in Japanese patients with pediatric GHD, including patients who switched to somatrogon from once-daily somatropin.Clinialtrials.gov:NCT03874013.

We review the recent remarkable progress of the molecular mechanisms of action of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) regarding their beneficial effects on older people and adrenal regenerative therapy by looking back on our research extending over 50 years since 1971. DHEAS is the most abundant circulating steroid hormone in humans and apes. DHEAS is essential for brain development in adrenarche and for anti-aging in adrenopause as shown by the evolutionary process in primates. The molecular mechanisms of action of DHEA and DHEAS have been clarified by the discovery of many membrane receptors and by the concept of intracrinological action, which is especially important in menopausal women. The genes associated with serum DHEAS concentrations were identified by genome-wide association study meta-analysis of cohort studies. Recent advances in aging research have shown that DHEA and DHEAS have anti-aging action via antioxidants, anti-inflammation, telomere protection, p38MAPK inhibition, anti-cortisol effects, and chaperone induction. DHEA has beneficial effects on the prevention of atherosclerosis based on visceral obesity-induced metabolic syndrome in middle-aged people. DHEA also prevents infection, frailty via reverse metabolism, sarcopenia, and osteoporosis in older people, with a marked decrease in serum DHEAS concentrations. This review discusses adrenal regenerative therapy using steroid-producing cell replacement by overexpressing Ad4BP/steroidogenic factor 1 in mouse or human bone marrow mesenchymal stem cells. This therapy replaces cortisol and DHEAS treatment for the prevention of sudden death by adrenal crisis and severe infection in primary adrenal insufficiency (Addison's disease).

The combination of methimazole (MMI) and potassium iodide (KI) is often used to improve the thyroid function more quickly in the initial medical treatment of Graves' disease when the levels of free T4 are ≥5.0 ng/dL. However, deterioration in the levels of free T3 and T4 was observed immediately after the cessation of KI. To avoid deterioration following cessation of KI, we investigated 150 drug-naïve patients with Graves' disease treated with a combination of MMI and KI. Patients administered KI for 3-17 weeks (median, 9 weeks) during the initial period were selected for this study. Levels of free T3 and T4 were determined before treatment, at the time of cessation of KI, and at 2-8 weeks (median, 4 weeks after cessation). In 35 of 150 patients (23.3%), the levels of free T3 and/or free T4 were elevated beyond the upper limit of each reference range after cessation of KI. In a multivariate regression analysis, the levels of free T3 and the ratio of the daily dose of KI (mg) to MMI (mg) at the cessation of KI were significantly lower (p < 0.0001, p = 0.0007) in patients without deterioration than in those with deterioration. The odds ratios were 0.175 (95% confidence interval [CI]: 0.072-0.381) and 0.675 (95% CI: 0.533-0.846), respectively. When the ratio of the dose of KI to MMI at cessation was ≤1.7, and the level of free T3 was ≤3.2 pg/mL, deterioration was avoided in 97.8% of patients.

The National Health Insurance Bureau in Taiwan introduced several initiatives to slow the progression of diabetic kidney disease (DKD) through early interventions and comprehensive patient education. This study evaluates the association of a multidisciplinary care and education model for patients with type 2 diabetes mellitus and early-stage DKD in Taiwan. A total of 355 participants enrolled in an integrated care program from May 2022 to September 2023 and followed up until April 2024 were analyzed. The intervention included personalized education, exercise management, dietary counseling, and multimedia tools aimed at improving disease self-management. The results demonstrated that compared to baseline, the patients with second follow-up data had lower systolic blood pressure (p < 0.001), lower diastolic blood pressure (p < 0.001), lower glycosylated hemoglobin A_1c (HbA_1c) (7.51% vs. 7.10%, p < 0.001), lower total cholesterol (p = 0.047), lower high-density lipoprotein cholesterol (p = 0.047), lower low-density lipoprotein (LDL) cholesterol (p = 0.009), lower estimated glomerular filtration rate (p < 0.001), lower log urine albumin to creatinine ratio (p < 0.001), used fewer types of antihypertensive agents (p < 0.001), more types of oral hypoglycemic agents (p = 0.045), more insulin (p < 0.001), and more statins (p = 0.029). These findings showed that the multidisciplinary care model significantly improved glycemic control, blood pressure, lipid profiles, and albuminuria in patients with type 2 diabetes and early-stage DKD. Specifically, reductions in HbA_1c, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, and albuminuria were achieved, underscoring the importance of a comprehensive team-based approach.

Adrenal hormones are essential for maintaining physiological homeostasis; however, imbalances in their production can significantly impact bone metabolism. This review examines how adrenal hormone dysregulation affects bone health, focusing on the following three key pathological conditions: autonomous cortisol secretion, primary aldosteronism, and pheochromocytoma/paraganglioma. Each disorder exerts distinct effects on bone metabolism, contributing to reduced bone mass, deteriorated bone quality, and increased fracture risk. Recent advances in steroid profiling and single-cell transcriptome analysis have revealed that, in adrenocortical adenomas-such as cortisol-producing and aldosterone-producing adenomas-multiple steroid hormones contribute to these effects rather than a single hormone. Additionally, age-related changes in steroid hormones, particularly the progressive decline in dehydroepiandrosterone sulfate production and alterations in cortisol circadian rhythm, may contribute to age-associated bone fragility. This review summarizes the effects of adrenal hormone imbalances on bone metabolism in both pathological conditions and aging, which may contribute to understanding adrenal-related osteoporosis.

GPT-4o, a general-purpose large language model, has a Retrieval-Augmented Variant (GPT-4o-RAG) that can assist in dietary counseling. However, research on its application in this field remains lacking. To bridge this gap, we used the Japanese National Examination for Registered Dietitians as a standardized benchmark for evaluation. Three language models-GPT-4o, GPT-4o-mini, and GPT-4o-RAG-were assessed using 599 publicly available multiple-choice questions from the 2022-2024 national examinations. For each model, we generated answers to each question five times and based our evaluation on these multiple outputs to assess response variability and robustness. A custom pipeline was implemented for GPT-4o-RAG to retrieve guideline-based documents for integration with GPT-generated responses. Accuracy rates, variance, and response consistency were evaluated. Term Frequency-Inverse Document Frequency analysis was conducted to compare word characteristics in correctly and incorrectly answered questions. All three models achieved accuracy rates >60%, the passing threshold. GPT-4o-RAG demonstrated the highest accuracy (83.5% ± 0.3%), followed by GPT-4o (82.1% ± 1.0%), and GPT-4o-mini (70.0% ± 1.4%). While the accuracy improvement of GPT-4o-RAG over GPT-4o was not statistically significant (p = 0.12), it exhibited significantly lower variance and higher response consistency (97.3% vs. 91.2-95.2%, p < 0.001). GPT-4o-RAG outperformed other models in applied and clinical nutrition categories but showed limited performance on numerical questions. Term Frequency-Inverse Document Frequency analysis suggested that incorrect answers were more frequently associated with numerical terms. GPT-4o-RAG improved response consistency and domain-specific performance, suggesting utility in clinical nutrition. However, limitations in numerical reasoning and individualized guidance warrant further development and validation.

Comparative endocrinology is a research subfield in endocrinology that delves into deeper understanding of the endocrine system from an evolutionary or phylogenetic perspective. To date, this approach has contributed significantly to the development of endocrinology by elucidating the evolutionary history of hormone molecules and their functions from invertebrates to vertebrates. In this review, the author initially introduces how the comparative approach has expanded and enlightened the view in endocrinology using the concept of hormones as an example. The expansion of the hormone concept blurs boundaries between signaling molecules of the three homeostatic systems, namely, the endocrine, nervous, and immune systems. Subsequently, the evolutionary history of the endocrine system is introduced in terms of both molecules and functions using the insulin superfamily as a model. This hormone family is one of the most ancient hormonal systems in animal (metazoan) phylogeny and the homologous hormones are identified in the most ancient metazoans such as sponges and hydra. In addition, this hormonal system was chosen as a topic of this review, because insulin is one of the most focused research topics in modern medicine in relation to insulin resistance and metabolic syndrome. Finally, the ancestral molecule of the insulin superfamily and its original or essential function will be discussed with some speculations to illustrate the value and joy of comparative studies that can create an original concept of the endocrine system from the evolutionary viewpoint. The comparative approach certainly helps deeper understanding of the insulin superfamily of humans.