The Journal of clinical endocrinology and metabolism最新文献

{"title":"Maternal obesity increases breast milk bile acid levels.","authors":"Lucie Marousez, Amandine Descat, Mostafa Kouach, Thameur Rakza, Philippe Deruelle, Bart Staels, Jean-François Goossens, Anne Tailleux, Delphine Eberlé","doi":"10.1210/clinem/dgaf559","DOIUrl":"https://doi.org/10.1210/clinem/dgaf559","url":null,"abstract":"<p><strong>Context: </strong>Breast milk (BM) provides the optimal combination of essential nutrients and bioactive molecules for infant growth and development. However, accumulating evidence from our group and others indicates that maternal factors such as obesity can alter BM composition, potentially affecting offspring health outcomes. Bile acids (BA), both primary and secondary, have been identified in human BM but the precise composition and their role in BM remain largely underexplored. In this study, we analyzed BA profiles in BM and plasma in lactating mothers with obesity or not, across two independent clinical cohorts.</p><p><strong>Methods: </strong>BM and plasma samples were collected from breastfeeding women classified as normal-weight (N) or with obesity (O). BA concentrations were quantified by reverse phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>BAs were present in BM, primarily as glyco- and tauro-conjugated of the primary BAs cholic (CA) and chenodeoxycholic acid (CDCA), though at lower levels than in plasma under normal-weight conditions. Maternal obesity led to a marked increase in total BM BA levels while plasma BA concentrations and composition remained unchanged. Additionally, BM BA levels were positively correlated with maternal pre-pregnancy BMI, circulating leptin (a marker of adiposity), and insulin levels.</p><p><strong>Conclusions: </strong>Our findings identify maternal obesity as a significant modifier of BM BA composition, with potential implications for neonatal digestion, maturation and health. Further research is warranted to elucidate the impact of these alterations on infant health and development.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Weight Change on Type 2 Diabetes Risk: A Prospective Study in a Japanese Population.","authors":"Takuya Kagisaki, Megu Y Baden, Asuka Oyama, Midori Noguchi, Hiroyasu Iso, Iichiro Shimomura","doi":"10.1210/clinem/dgaf558","DOIUrl":"https://doi.org/10.1210/clinem/dgaf558","url":null,"abstract":"<p><strong>Context: </strong>Although weight reduction has been shown to reduce type 2 diabetes risk, the threshold of weight change, including increase and decrease, associated with the risk remained unclear.</p><p><strong>Objective: </strong>We investigated the association between weight change and the risk of type 2 diabetes.</p><p><strong>Methods: </strong>The participants were 41,539 nondiabetic residents (16,914 men, 24,625 women) in Kochi, Japan, who underwent health examinations between April 2013 and March 2015. The association between 1-year weight change and the risk of type 2 diabetes was assessed using Cox proportional hazards models.</p><p><strong>Results: </strong>During a mean 5.7-year follow-up, 3,564 new-onset type 2 diabetes cases were documented.　Compared with participants with stable body weight (<1.0 % change), those with weight decreases of 1.0%-2.9%, 3.0%-4.9% and ≥5.0% showed a lower risk of type 2 diabetes [16% (8%-24%, p<0.001), 25% (15%-34%, p<0.001), and 26% (14%-36%, p<0.001), respectively]. Conversely, those with weight increases of 1.0%-2.9%, 3.0%-4.9% and ≥5.0% showed a higher risk [15% (4%-26%, p=0.005), 35% (20%-53%, p<0.001), and 51% (29%-76%, p<0.001), respectively]. These associations persisted among individuals with BMI ≥25 kg/m2 or ≥10 kg weight gain since age 20. Among individuals with BMI 22-25 kg/m2, weight increase of ≥3.0% showed a higher risk. No associations were observed in individuals with BMI <22 kg/m2 or aged ≥75.</p><p><strong>Conclusion: </strong>Both preventing weight gain and reducing weight are important for lowering the risk of type 2 diabetes in Japanese individuals, particularly among those with BMI ≥22kg/m2.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Obesity with the Multi-Omics Score: From Solo to Orchestra.","authors":"Hari Krishna Yalamanchili, David B Allison","doi":"10.1210/clinem/dgaf557","DOIUrl":"https://doi.org/10.1210/clinem/dgaf557","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum proteomics of insulin resistance disorders distinguish MASLD from lipodystrophy and insulin receptor defects.","authors":"Maria Mironova, Allison Wing, Brent S Abel, Maren C Podszun, Rebecca J Brown, Yaron Rotman","doi":"10.1210/clinem/dgaf516","DOIUrl":"https://doi.org/10.1210/clinem/dgaf516","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to obesity, metabolic syndrome and insulin resistance (IR). In IR associated with obesity or lipodystrophy (LD), caused by missing adipose tissue), hyperinsulinemia stimulates hepatic lipogenesis, causing steatotic liver disease (SLD). In contrast, insulin receptor pathogenic variants (INSR), despite hyperinsulinemia and IR, do not promote hepatic lipogenesis and steatosis. We aimed to understand SLD pathophysiology by comparing serum proteomic signatures of MASLD, LD, and INSR.</p><p><strong>Methods: </strong>Single-center study of fasting serum proteome using SomaScan assay in 30 LD, 29 INSR, and 16 people with MASLD. Key targets were assessed in the hepatic transcriptome of MASLD patients (n=19) and in HepG2 cells.</p><p><strong>Results: </strong>Of 6,412 proteins, 567 differed between at least two groups. The proteome profiles clearly separated INSR from the other groups, while MASLD and LD displayed similarity, primarily in proteins involved in metabolism, liver injury, and fibrosis. Several proteins were uniquely elevated in INSR and LD compared to MASLD, particularly Factor IX (F9) and liver-expressed antimicrobial peptide 2 (LEAP2). Serum levels of F9 and LEAP2 correlated with their hepatic expression, with in-vitro expression unaffected by leptin, insulin, or glucose treatment.</p><p><strong>Conclusions: </strong>This first comparative proteomics study identified shared and unique pathways in IR disorders. MASLD and LD share features, suggesting similar drivers of liver disease progression. Key liver-derived proteins differ between MASLD, INSR and LD, due to unique disorder features. We demonstrate the utility of proteomics and rare disorder studies in interrogating pathogenesis of common disorders like MASLD.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparable Outcomes of Differentiated Thyroid Cancer in Immunocompromised versus Immunocompetent Patients.","authors":"Amit Ritter, Alana Eagan, Helena Levyn, R Michael Tuttle, Snehal Patel, Ian Ganly","doi":"10.1210/clinem/dgaf550","DOIUrl":"https://doi.org/10.1210/clinem/dgaf550","url":null,"abstract":"<p><strong>Background: </strong>Differentiated thyroid cancer (DTC) is generally a highly treatable malignancy with low mortality and a favorable prognosis. However, the impact of immunodeficiency on DTC outcomes remains poorly understood, with research largely limited to organ transplant recipients. This study aimed to address this gap by comparing the clinical characteristics and outcomes of DTC in immunocompromised patients with a propensity matched cohort of immunocompetent individuals.</p><p><strong>Methods: </strong>The study compared adult patients with DTC and pre-existing immunodeficiencies treated at Memorial Sloan-Kettering Cancer Center between 1987 and 2020 to a propensity-matched control group of immunocompetent patients, with a 5:1 comparison ratio. Data on demographics, disease characteristics, and outcomes were analyzed.</p><p><strong>Results: </strong>Among 8,534 DTC patients, 130 (1.5%) were immunocompromised. After propensity score matching, 650 immunocompetent patients were included for comparison. Recurrence-free survival did not differ significantly between groups (p = 0.94), with recurrence rates remaining below 10% in both cohorts over 180 months. At 10 years, disease-specific survival was also similar (p = 0.34), with rates of 100% for immunocompromised and 98% for immunocompetent patients.</p><p><strong>Conclusions: </strong>DTC has a comparable prognosis in immunocompetent and immunocompromised patients.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Puberty Suppression and Sex Steroids on Weight, BMI, and Lipid Profiles in Danish Transgender Adolescents.","authors":"Kjersti Kvernebo Sunnergren, Pernille Badsberg Norup, Mette Ewers Haahr, Annamaria Giraldi, Anne Katrine Pagsberg, Peter Christiansen, Lise Aksglaede, Line Cleemann, Anders Juul, Katharina M Main","doi":"10.1210/clinem/dgaf549","DOIUrl":"https://doi.org/10.1210/clinem/dgaf549","url":null,"abstract":"<p><strong>Context: </strong>Cardiovascular health of the transgender population receiving hormone therapy (HT) has been a concern.</p><p><strong>Objective: </strong>To investigate weight, BMI, and lipid profiles in a national cohort of transgender adolescents starting HT before 18 years of age.</p><p><strong>Methods: </strong>In this observational study, 164 trans boys and 55 trans girls were followed longitudinally during HT. Gonadotropin-releasing hormone analog (GnRHa) was initiated either before or alongside sex steroid therapy. Anthropometry and lipid profiles were analyzed at the start of HT and at routine visits.</p><p><strong>Results: </strong>Before HT, overweight (BMI 1-2 standard deviation score (SDS)) and obesity (BMI ≥2SDS) were found in 26.8% and 22.0% of trans boys, and in 5.7% and 5.7% of trans girls, respectively. BMI SDS correlated positively with total cholesterol, low-density lipoprotein (LDL), and triglycerides, and negatively with high-density lipoprotein (HDL). In trans boys and girls, high percentages had lipids above normal reference intervals; total cholesterol (12.5% and 6.1%), LDL (21.8% and 12.5%), and triglycerides (3.4% and 6.3%), and HDL below normal reference intervals (9.0% and 18.4%), respectively. During GnRHa monotherapy, there was a tendency for declining weight SDS, but BMI SDS, and lipid profiles did not change consistently. After the initiation of sex steroids, weight SDS, BMI SDS, and HDL decreased along with increased triglycerides in trans boys, and increased HDL in trans girls.</p><p><strong>Conclusion: </strong>Overweight, obesity, and dyslipidemia were common in transgender adolescents before HT was initiated. BMI did not deteriorate, but dyslipidemia worsened slightly during sex steroid therapy in trans boys but not in trans girls.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Machine Learning-Based Model for Methimazole Dosage Adjustment in Youth with Hyperthyroidism.","authors":"Joon Young Kim, Kanghyuck Lee, Eunsik Choi, Jun Suk Oh, Eun Byoul Lee, Hyun Wook Chae, Taehoon Ko, Kyungchul Song","doi":"10.1210/clinem/dgaf542","DOIUrl":"https://doi.org/10.1210/clinem/dgaf542","url":null,"abstract":"<p><strong>Context: </strong>Accurate methimazole (MMI) dose adjustment in pediatric hyperthyroidism is crucial, but individualized titration relies on clinician experience due to a lack of validated predictive tools.</p><p><strong>Objective: </strong>This study aimed to develop and validate machine learning-based models for predicting optimal MMI dosage in pediatric hyperthyroidism.</p><p><strong>Design: </strong>This was a retrospective, multicenter, model-development study. Machine learning models, including linear regression, decision tree, support vector regression, eXtreme Gradient Boosting (XGBoost), and feed-forward neural networks, were trained and validated.</p><p><strong>Setting: </strong>Data were collected from a primary center for model training, with two separate centers providing data for external validation.</p><p><strong>Patients or other participants: </strong>Data were derived from 1,512 visits for the training set, and 666 and 31 visits for two external validation cohorts, respectively. All data were from youth aged ≤18 years with hyperthyroidism.</p><p><strong>Interventions: </strong>The models were trained to predict the optimal daily dosage of MMI based on variables including age, sex, anthropometric measures, prior MMI dosage, treatment duration, current and previous results of thyroid function tests.</p><p><strong>Main outcome measures: </strong>Model performance was evaluated by the mean absolute error (MAE) between the predicted and actual MMI dosages. Feature importance was determined using Shapley additive explanations (SHAP) analysis.</p><p><strong>Results: </strong>The XGBoost model demonstrated the best performance in both internal validation (MAE, 1.72 mg) and external validation (MAE, 1.08 mg). SHAP analysis identified previous MMI dose, triiodothyronine, and free thyroxine levels as key predictors.</p><p><strong>Conclusions: </strong>This study introduces the first data-driven tool to guide MMI dosing in pediatric hyperthyroidism which can improve clinical efficiency.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osilodrostat-associated Adrenal Gland Shrinkage: a Case Series of Patients with ACTH-Dependent Cushing's Syndrome.","authors":"Elena V Varlamov, Brian J Park, Maria Fleseriu","doi":"10.1210/clinem/dgaf552","DOIUrl":"https://doi.org/10.1210/clinem/dgaf552","url":null,"abstract":"<p><strong>Context: </strong>Medical therapy for Cushing's syndrome (CS) is increasingly used. A potent adrenal steroidogenesis inhibitor, osilodrostat, has been rarely linked to prolonged adrenal insufficiency (AI).</p><p><strong>Objective: </strong>We hypothesized that osilodrostat-induced adrenal insufficiency could be associated with adrenal gland shrinkage.</p><p><strong>Design: </strong>Non-interventional, retrospective, longitudinal, IRB-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000 and July 1, 2025.</p><p><strong>Setting: </strong>Ambulatory and inpatient, academic, quaternary medical center.</p><p><strong>Patients or other participants: </strong>Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and CT imaging before and after osilodrostat available for adrenal volume (AV) measurement.</p><p><strong>Intervention(s): </strong>Age, sex, osilodrostat doses and duration, laboratory data and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.</p><p><strong>Main outcome measure(s): </strong>AV before and after initiation of osilodrostat was expressed as percent reduction.</p><p><strong>Results: </strong>10 patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing's disease) were included. Osilodrostat mean starting, maximum and final doses: 7.7, 13.8 and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7±22.2% from 25.5±9.9 ml to 12.7±6.4 ml, p<0.001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r=0.626, p=0.027.</p><p><strong>Conclusions: </strong>We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: \"Triglyceride-Glucose Index and Risks of All-Cause and Cause-Specific Mortality in Young Adults\".","authors":"","doi":"10.1210/clinem/dgaf543","DOIUrl":"10.1210/clinem/dgaf543","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen Presenting Cell Isolevuglandins Link Salt-Sensitivity of Blood Pressure to Insulin Resistance.","authors":"Lale A Ertuglu, Mert Demirci, Ashley L Mutchler, Cheryl L Laffer, Mohammad Saleem, T Alp Ikizler, Annet Kirabo","doi":"10.1210/clinem/dgaf556","DOIUrl":"https://doi.org/10.1210/clinem/dgaf556","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance has been associated with salt sensitivity and low sodium intake; however, the mechanisms remain elusive. Our previous studies showed that sodium-induced isolevuglandin (IsoLG) formation in antigen-presenting cells (APCs) leads to systemic inflammation and salt-sensitive hypertension and IsoLG formation in APCs is affected by acute alterations in salt intake in salt-sensitive but not salt-resistant people. In this clinical study, we investigated how acute salt loading and depletion change insulin resistance markers and whether these changes are linked with changes in IsoLGs in APCs.</p><p><strong>Methods: </strong>20 participants with hypertension underwent an inpatient protocol of salt loading and depletion for assessment of salt sensitivity. Plasma glucose and insulin levels were measured after 24 hours of salt loading and depletion and insulin resistance was measured by the homeostasis model assessment index (HOMA-IR). IsoLG-adduct accumulation in APCs (dendritic cells, classical, intermediate and non-classical monocytes) was assessed by flow cytometry.</p><p><strong>Results: </strong>Baseline insulin resistance correlated with higher salt sensitivity. Insulin resistance significantly increased from salt loading to salt depletion. Salt-depletion induced changes in IsoLG+ APCs significantly correlated with changes in HOMA-IR. This correlation was significant only in participants who were insulin resistant at baseline.</p><p><strong>Conclusion: </strong>Within 24 hours of acute salt depletion, markers of insulin resistance exhibit a significant increase, which strongly correlates with change in IsoLG formation in APCs. This finding implies that oxidative stress in APCs may be implicated in the salt-sensitive modulation of glucose metabolism.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}