Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Elevated 1-hour Post Load Glucose as a Predictor for Telomere Attrition: A Study Based on a Chinese Community Population.","authors":"Qi Gao, Jie Yu, Yiwen Liu, Baodi Xing, Fan Ping, Lingling Xu, Wei Li, Huabing Zhang, Yuxiu Li","doi":"10.1210/clinem/dgae748","DOIUrl":"10.1210/clinem/dgae748","url":null,"abstract":"<p><strong>Context: </strong>One-hour post-load glucose (1h-PG) detects dysglycemia-related disorders more effectively than traditional glycemic parameters. Hyperglycemia accelerates aging, but whether 1h-PG outperforms in predicting aging remains unclear.</p><p><strong>Objective: </strong>To compare the effectiveness of 1h-PG with other glycemic parameters in identifying and predicting telomere attrition.</p><p><strong>Methods: </strong>We conducted a cross-sectional and longitudinal study based on a Chinese community cohort. Multivariate linear regression and logistic regression were used to analyze the associations between glycemic parameters and telomere length. The area under the receiver operating characteristic (AUROC) curve were used to compare the differentiating and predictive ability. Populations were regrouped by glucose tolerance status and 1h-PG to compare telomere length. Analyses were separately conducted in nondiabetic and diabetic populations.</p><p><strong>Results: </strong>The cross-sectional study included 715 participants. Only 1h-PG was significantly negatively associated with relative telomere length in both nondiabetic [β = -.106, 95% confidence interval (CI) -0.068 to -0.007, P = .017] [odds ratio (OR) = 1.151, 95% CI 1.069 to 1.239, P = .005] and diabetic (β = -.222, 95% CI -0.032 to -0.007, P = .002) (OR = 1.144, 95% CI 1.041 to 1.258, P = .035) populations. The longitudinal study recruited 437 populations and 112 remained in 7-years follow-up. 1h-PG was associated with telomere shortening in the nondiabetic group (β = -.314, 95% CI -0.276 to -0.032, P = .016) (OR = 2.659, 95% CI 1.158 to 6.274, P = .021). AUROC analysis showed that 1h-PG outperformed other glycemic parameters in identifying and predicting telomere attrition. Reclassification revealed that normal glucose tolerance and prediabetic individuals with elevated 1h-PG had telomere lengths comparable to prediabetic and diabetic populations, respectively.</p><p><strong>Conclusion: </strong>1h-PG outperforms other glycemic parameters in predicting telomere attrition and can be a valuable marker for early aging detection.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2285-e2297"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Variation in LMNA Underlies Polycystic Ovary Syndrome Pathogenesis in 2 Independent Cohorts.","authors":"Rosemary Bauer, Chloe Parker, Lidija K Gorsic, Michael Geoffrey Hayes, Allen R Kunselman, Richard S Legro, Corrine K Welt, Margrit Urbanek","doi":"10.1210/clinem/dgae761","DOIUrl":"10.1210/clinem/dgae761","url":null,"abstract":"<p><strong>Context: </strong>Polycystic ovary syndrome (PCOS) is a common, heritable endocrinopathy that is a common cause of anovulatory infertility in reproductive age women. Variants in LMNA cause partial lipodystrophy, a syndrome with overlapping features to PCOS.</p><p><strong>Objective: </strong>We tested the hypothesis that rare variation in LMNA contributes to PCOS pathogenesis and selects a lipodystrophy-like subtype of PCOS.</p><p><strong>Methods: </strong>We sequenced LMNA by targeted sequencing a Discovery cohort of 811 PCOS patients and 164 healthy controls. We then analyzed LMNA from whole-exome sequencing of a Replication cohort of 718 PCOS patients and 281 healthy controls. We evaluated variation in the LMNA gene and hormone and lipid profiles of participants.</p><p><strong>Results: </strong>In the Discovery cohort, we identified 8 missense variants in 15/811 cases, and 1 variant in 1/172 reproductively healthy controls. There is strong evidence for association between the variants and PCOS compared to gnomAD non-Finnish European population controls (χ2 = 17, P = 3.7 × 10-5, OR = 2.9). In the Replication cohort, we identified 11 unique variants in 15/718 cases, and 1 variant in 281 reproductively healthy controls. Again, there is strong evidence for association with population controls (χ2 = 30.5, P = 3.4 × 10-8, OR = 4.0). In both the Discovery and Replication cohorts, variants in LMNA identify women with PCOS with high triglycerides and extreme insulin resistance.</p><p><strong>Conclusion: </strong>Rare missense variation in LMNA is reproducibly associated with PCOS and identifies some individuals with lipodystrophy-like features. The overlap between this PCOS phenotype and genetic partial lipodystrophy syndromes warrants further investigation into additional lipodystrophy genes and their potential in PCOS etiology.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2217-e2232"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations and Clinical Value of Peripheral Lymphocyte Subsets and Inflammatory Factors in Paragangliomas.","authors":"Yue Zhou, Wenqian Zhang, Yunying Cui, Tianyi Li, Yu Wang, Ming Li, Anli Tong","doi":"10.1210/clinem/dgae702","DOIUrl":"10.1210/clinem/dgae702","url":null,"abstract":"<p><strong>Objectives: </strong>Given the pivotal role of immune and inflammatory responses in tumor patients, the present study aimed to explore alterations and the clinical value of peripheral lymphocyte subsets and inflammatory factors in pheochromocytomas/paragangliomas (PPGLs).</p><p><strong>Methods: </strong>The clinical data of 327 patients, including 102 patients with metastatic PPGLs, were retrospectively analyzed. Peripheral lymphocyte subsets were determined by flow cytometry. Relationships between immune and inflammatory parameters and clinicopathological characteristics were evaluated by intergroup comparisons and correlation analyses. Univariate and multivariate logistic regression analyses were employed to identify metastatic indicators. The corresponding nomogram was constructed and evaluated for discrimination and calibration.</p><p><strong>Results: </strong>The median age at diagnosis was 45.0 years, and duration of follow-up was 3.0 years. Compared with those in younger patients (< 45.0 years), most lymphocyte subsets were significantly reduced in older patients (≥ 45 years) (P < .05). The count of lymphocytes, CD3+ T cells and CD4+ T cells were negatively correlated with 24-hour urinary epinephrine and plasma metanephrine levels (R = -0.2 ∼ 0.1, P < .05). In addition, patients with lymph node (n = 37) or bone metastases (n = 41) had a lower percentage of CD4+ T cells (P < .05). Multivariate analysis revealed that CD3+ T cell count ≥ 1446.50/μL, CD4+ T cell% < 39.95%, CD8+ T cell% < 24.95%, CD4+/CD8+ T cell ratio < 2.88, B cell% ≥ 8.65%, TNF-alpha < 12.45 pg/mL, IL-8 < 30.50 pg/mL, and platelets ≥ 269.50 × 109/L were significant indicators of metastatic PPGLs. The area under the curve (AUC) of the nomogram was 0.800 (95% CI: 0.736-0.865).</p><p><strong>Conclusion: </strong>Immunosenescence, characterized by immune dysfunction with aging, was observed in PPGLs. Higher epinephrine and metanephrine levels might impair host immune response. Monitoring changes in peripheral lymphocyte subsets and serum cytokines could indicate patients' conditions, especially the occurrence of metastasis.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1952-1963"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Peripancreatic Adipose Tissue Paracrine Signaling Impacts Insulin Secretion, Blood Flow, and Gene Transcription.","authors":"Bryan C Bergman, Karin Zemski Berry, Amanda Garfield, Amy Keller, Simona Zarini, Sophia Bowen, Colleen McKenna, Darcy Kahn, Jay Pavelka, Emily Macias, Charis Uhlson, Chris Johnson, Holger A Russ, Carlos H Viesi, Marcus Seldin, Chengyang Liu, Nicolai M Doliba, Jonathan Schoen, Kevin Rothchild, Kweku Hazel, Ali Naji","doi":"10.1210/clinem/dgae767","DOIUrl":"10.1210/clinem/dgae767","url":null,"abstract":"<p><strong>Context: </strong>Adipose tissue accumulation around nonadipose tissues is associated with obesity and metabolic disease. One relatively unstudied depot is peripancreatic adipose tissue (PAT) that accumulates in obesity and insulin resistance and may impact β-cell function. Pancreatic lipid accumulation and PAT content are negatively related to metabolic outcomes in humans, but these studies are limited by the inability to pursue mechanisms.</p><p><strong>Objective: </strong>We obtained PAT from human donors through the Human Pancreas Analysis Program to evaluate differences in paracrine signaling compared to subcutaneous adipose tissue (SAT), as well as effects of the PAT secretome on aortic vasodilation, human islet insulin secretion, and gene transcription using RNA sequencing.</p><p><strong>Results: </strong>PAT had greater secretion of interferon-γ and most inflammatory eicosanoids compared to SAT. Secretion of adipokines negatively related to metabolic health were also increased in PAT compared to SAT. We found no overall effects of PAT compared to SAT on human islet insulin secretion; however, insulin secretion was suppressed after PAT exposure from men compared to women. Vasodilation was significantly dampened by PAT conditioned media, an effect explained almost completely by PAT from men and not women. Islets treated with PAT showed selective changes in lipid metabolism pathways while SAT altered cellular signaling and growth. RNA sequencing analysis showed changes in islet gene transcription impacted by PAT compared to SAT, with the biggest changes found between PAT based on sex.</p><p><strong>Conclusion: </strong>The PAT secretome is metabolically negative compared to SAT, and impacts islet insulin secretion, blood flow, and gene transcription in a sex-dependent manner.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2233-e2247"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Sodium-glucose Transporter 2 Inhibitors on Cardiovascular Outcomes in Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Songwei Wang, Yueqi Zhang, Abudunaibi Balati, Bing Li, Lei Dai, Dan Yu","doi":"10.1210/clinem/dgaf016","DOIUrl":"10.1210/clinem/dgaf016","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease is a major cause of increasing morbidity and mortality in type 1 diabetes mellitus (T1DM). Although insulin therapy is the cornerstone of T1DM, its difficult use and narrow therapeutic index make it difficult for patients to reach glycated hemoglobin targets, increasing the risk of cardiovascular events. Therefore, the combination of sodium-glucose transporter 2 inhibitors (SGLT2i) can likely improve or provide more cardiovascular benefits to patients with T1DM.</p><p><strong>Methods: </strong>This study conducted a systematic review and meta-analysis of randomized controlled trials published in PubMed, Scopus, Cochrane Library, Web of Science, and Embase up to June 30, 2024. The data from eligible trials were summarized as mean difference (MD) and SD for continuous methods and 95% CI and risk ratio (RR) for dichotomous approaches.</p><p><strong>Results: </strong>There were 16 articles that met the inclusion criteria. Compared with placebo, SGLT2i significantly reduced glycated hemoglobin levels (MD: -0.40%, 95% CI, -0.44 to -0.36; P < .00001, I2 = 37%), and body weight (MD: -3.31 kg, 95% CI, -3.67 to -2.96; P < .00001, I2 = 70%) in insulin-using patients with T1DM, and did not significantly increase the risk of hypoglycemia and severe hypoglycemia. It should be noted that SGLT2i significantly increased the risk of diabetic ketoacidosis acidosis (RR: 4.45, 95% CI, 2.81-7.05, P < .00001, I2 = 0%).</p><p><strong>Conclusion: </strong>SGLT2i not only significantly improved glycated hemoglobin and body weight in patients with T1DM but also significantly increased the risk of diabetic ketoacidosis acidosis.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2071-2081"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Lipid Dysregulation in Tangier Disease: A Case Series and Metabolic Characterization.","authors":"","doi":"10.1210/clinem/dgaf235","DOIUrl":"10.1210/clinem/dgaf235","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2431"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: \"Testosterone Treatment and Sexual Function in Men: Secondary Analysis of the T4DM (Testosterone for Diabetes) Trial\".","authors":"","doi":"10.1210/clinem/dgaf205","DOIUrl":"10.1210/clinem/dgaf205","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2433"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor From Zhang et al: \"Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer\".","authors":"Yaoyu Zhang, Yingying Zhao, Tao Deng, Wenjun Meng","doi":"10.1210/clinem/dgaf220","DOIUrl":"10.1210/clinem/dgaf220","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2422"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Level Mosaic GCK Mutations in Children With Diazoxide-Unresponsive Congenital Hyperinsulinism.","authors":"Kara E Boodhansingh, Katherine Lord, N Scott Adzick, Tricia Bhatti, Arupa Ganguly, Charles A Stanley, Diva D De Leon","doi":"10.1210/clinem/dgae713","DOIUrl":"10.1210/clinem/dgae713","url":null,"abstract":"<p><strong>Context: </strong>Some children with diazoxide-unresponsive congenital hyperinsulinism (HI) lack any detectable disease-causing mutation in peripheral-blood DNA.</p><p><strong>Objective: </strong>This work aimed to examine whether somatic postzygotic mutations of known HI genes are responsible for disease in children with diazoxide-unresponsive HI requiring surgery with histology not classified as focal or localized islet nuclear enlargement (LINE), and without detectable mutations by standard genetic testing of peripheral blood DNA.</p><p><strong>Methods: </strong>Next-generation sequencing (NGS) was performed on specimens of pancreas from 10 children with diazoxide-unresponsive HI.</p><p><strong>Results: </strong>Four unique GCK mutations were identified at low levels of mosaicism ranging from 4.4% to 10.1% in pancreatic DNA from 5 of these 10 children. The GCK mutations were not detectable in peripheral-blood DNA by NGS in 3 cases from which peripheral-blood DNA was available for testing. All 4 GCK mutations have been previously published as activating HI mutations. The histology was consistent with diffuse HI in 4 of the 5 cases with mosaic GCK mutations. In one of these, hypomethylation of IC2 on chromosome 11p was identified in pancreatic and peripheral-blood DNA. Histology of the fifth case revealed minor islet abnormalities suggestive of Beckwith-Wiedemann spectrum although molecular analysis for 11pUPD was negative in pancreas.</p><p><strong>Conclusion: </strong>These results indicate that postzygotic somatic GCK mutations are responsible for some cases of nonfocal diazoxide-unresponsive HI.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1923-1928"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of AMH in Midreproductive Years with Bone Mineral Density and Turnover Markers in Midlife.","authors":"Siwen Wang, Elaine W Yu, Marie-France Hivert, Sheryl L Rifas-Shiman, Jan L Shifren, Maryam Kazemi, Emily Oken, Jorge E Chavarro","doi":"10.1210/clinem/dgae694","DOIUrl":"10.1210/clinem/dgae694","url":null,"abstract":"<p><strong>Context: </strong>The concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during midreproductive years predicts bone health over a decade later is unknown.</p><p><strong>Objective: </strong>To study the association of AMH levels in midreproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up.</p><p><strong>Methods: </strong>We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and type I collagen cross-linked C telopeptide (CTX-I).</p><p><strong>Results: </strong>In linear regression models adjusted for demographics and lifestyle, compared with women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI] spine: -.06 [-0.10, -0.02]; hip: -.05 [-0.08, -0.02]; femoral neck: -.03 [-0.06, 0.00]) and higher bone turnover markers (beta [95% CI] PINP: .36 SD [0.10, 0.63]; CTX-I: .34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among postmenopausal women in contrast to associations with bone turnover markers, which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up.</p><p><strong>Conclusion: </strong>Lower AMH during midreproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during midreproductive years may be a valuable predictor of long-term bone health.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1836-1845"},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}