Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"New insights on the environment of sex steroids in adipose tissue of postmenopausal women at hormone therapy.","authors":"Poli Mara Spritzer, Betânia Rodrigues Dos Santos","doi":"10.1210/clinem/dgae758","DOIUrl":"https://doi.org/10.1210/clinem/dgae758","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512187","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":"Investigation of Fibrillar Aggregates Formed by Pathogenic Pre-Pro-Vasopressin Mutants that Cause ADNDI.","authors":"Refika Dilara Vaizoglu, Beril Erdem, Mehmet Gul, Ceren Acar, Huseyin Ozgur Ozdemirel, Emel Saglar Ozer, Hatice Mergen","doi":"10.1210/clinem/dgae749","DOIUrl":"https://doi.org/10.1210/clinem/dgae749","url":null,"abstract":"<p><strong>Context: </strong>Aggregations of unfolded or misfolded proteins, both inside and outside cells, are implicated in numerous diseases, collectively known as amyloidosis. Particularly, Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare disease caused by mutations in the AVP-NPII gene, leading to the inability to secrete arginine vasopressin (AVP). These misfolded proteins accumulate within the endoplasmic reticulum (ER), causing cellular dysfunction.</p><p><strong>Objective: </strong>This study aimed to investigate the formation of amyloid-like aggregates within the cell resulting from misfolded mutant precursor proteins, which induce disulfide-linked oligomers due to the G45C, 207_209delGGC, G88V, C98X, C104F, E108D-1, E108D-2 and R122H mutations identified by our group in the AVP-NPII gene of ADNDI patients.</p><p><strong>Methods: </strong>De-glycosylation studies were performed to analyze the glycosylation patterns of mutant protein precursors. The involvement of these precursors in the ER-related degradation pathway was studied by conducting protease inhibition experiments. Disulfide-linked oligomer analysis determined the oligomerization status of the mutant precursors. Immunofluorescence and electron microscopy studies provided evidence of aggregate structures in the ER lumen. In vitro studies involving bacterial expression and fibril formation in E. coli.</p><p><strong>Results: </strong>Our findings demonstrated that the N-glycan structure of mutant precursors remains intact within the ER. Protease inhibition experiments indicated the involvement of these precursors in the ER-related degradation pathway. Disulfide-linked oligomer analysis revealed homo-oligomer structures in mutations. Immunofluorescence and electron microscopy studies confirmed the presence of aggregate structures in the ER lumen. In vitro studies showed that mutant precursors could form fibril structures in E. coli.</p><p><strong>Conclusion: </strong>Our study may support the idea that ADNDI belongs to the group of neurodegenerative diseases due to the formation of fibrillar amyloid aggregates in the cell.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512186","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":"Gestational exposure to PFAS, the \"Forever Chemicals,\" May Have \"Forever\" Health Impacts.","authors":"Erin LeBlanc","doi":"10.1210/clinem/dgae743","DOIUrl":"https://doi.org/10.1210/clinem/dgae743","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512184","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":"Ascertainment, awareness and intersection: PA meets PTC.","authors":"Peter J Fuller, Michael Mond, Jun Yang","doi":"10.1210/clinem/dgae755","DOIUrl":"https://doi.org/10.1210/clinem/dgae755","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512178","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":"Safety, Growth and Development After Dapagliflozin or Saxagliptin in Children With Type 2 Diabetes (T2NOW Follow-Up).","authors":"Naim Shehadeh, Pietro Galassetti, Nayyar Iqbal, Cecilia Karlsson, John Monyak, Jennifer Ostridge, Marie Bolin, Timothy Barrett","doi":"10.1210/clinem/dgae723","DOIUrl":"https://doi.org/10.1210/clinem/dgae723","url":null,"abstract":"<p><strong>Context: </strong>The T2NOW trial of dapagliflozin or saxagliptin versus placebo in pediatric patients with type 2 diabetes (T2D) demonstrated promising efficacy data for dapagliflozin and did not raise any safety concerns over 52 weeks.</p><p><strong>Objective: </strong>Assess long-term effects of prior dapagliflozin/saxagliptin administration on safety, growth and development.</p><p><strong>Design: </strong>Multicenter, randomized, double-blind phase 3 trial (T2NOW).</p><p><strong>Patients: </strong>210 children with T2D aged 10-17 years, followed for up to one year after treatment.</p><p><strong>Interventions: </strong>Previous treatment with once-daily dapagliflozin (5, 10 mg), saxagliptin (2.5, 5 mg) or placebo as add-on to diet, exercise, metformin and/or insulin for 52 weeks, plus a 52-week non-treatment follow-up period.</p><p><strong>Main outcome measures: </strong>Change in height, weight, body mass index (BMI), Tanner staging, growth and maturation markers, bone biomarkers and adverse events (AEs) from baseline to Week 104.</p><p><strong>Results: </strong>As expected in a pediatric population, mean height and weight slightly increased from baseline to Week 104. BMI remained generally stable; Changes were similar across treatment groups. Sexual maturation progressed normally to Week 104, with similar shifts between Tanner stages and changes in growth and maturation markers and bone biomarkers across groups. The proportion of patients reporting ≥1 AE during the non-treatment follow-up period was similar across groups previously treated with dapagliflozin (18.5%) or saxagliptin (15.9%) compared to placebo (21.1%). No deaths occurred.</p><p><strong>Conclusion: </strong>Prior treatment with dapagliflozin or saxagliptin for 52 weeks did not raise any safety concerns relating to height, weight, BMI, Tanner staging, growth and maturation markers, bone biomarkers or AEs for up to 52 weeks following treatment discontinuation, in pediatric patients with T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512198","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":"Heterogeneity of gestational diabetes and risk for adverse pregnancy outcome: a cohort study.","authors":"Yixin Gong, Qunhua Wang, Suyu Chen, Yujie Liu, Chenghua Li, Rong Kang, Jing Wang, Tian Wei, Qin Wang, Xianming Li, Sihui Luo, Jianping Weng, Xueying Zheng, Yu Ding","doi":"10.1210/clinem/dgae754","DOIUrl":"https://doi.org/10.1210/clinem/dgae754","url":null,"abstract":"<p><strong>Context: </strong>Diabetes has increasingly been recognized as a heterogeneous disease, with clinical characteristics and outcomes risk varying across different phenotypes. Evidence on heterogeneity of gestational diabetes (GDM) is yet to be provided.</p><p><strong>Objective: </strong>To investigate the insulin physiology and pregnancy outcomes of GDM phenotypes characterized by fasting hyperglycemia or postload hyperglycemia.</p><p><strong>Methods: </strong>A total of 2050 women who underwent a 75-g oral glucose tolerance test were prospectively recruited and followed up until delivery. Women were categorized into normoglycemia (NGT, n = 936), isolated impaired fasting glucose (gestational-IFG, n = 378), and isolated impaired postload glucose tolerance (gestational-IGT, n = 736) groups. Fasting blood sample at mid-pregnancy were collected to measure C-peptide and insulin concentrations. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate insulin physiology. Maternal and neonatal outcomes were recorded.</p><p><strong>Results: </strong>Gestational-IFG had greater insulin resistance (HOMA-IR 3.11 vs. 2.25, QUICKI-CP 0.94 vs. 1.03, both P < 0.01), and gestational-IGT had worse β-cell function (C-peptide 2.00 vs. 2.26 ng/ml, P < 0.05) when compared to one another. Gestational-IFG was more strongly associated with excessive gestational weight gain (RR 1.62, 95% CI 1.18-2.23) and large-for-gestational-age infants (RR 1.45, 95% CI 1.03-2.03) than gestational-IGT. The risk for neonatal brain injury was increased in gestational-IGT (RR 2.03, 95% CI 1.04-4.09), but not in gestational-IFG (P = 0.439). Gestational-IGT showed a stronger association with the risk of preterm birth compared to gestational-IFG (RR 1.80, 95% CI 1.02-3.36).</p><p><strong>Conclusion: </strong>GDM exhibits distinct insulin physiology profiles. Pregnancy outcome varies between each phenotype. These findings provide evidence on risk stratification and diverse strategies for the treatment of GDM.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512185","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":"Cost-Effectiveness Analysis Comparing Conventional and Digital Software Supported Management for Hypothyroidism.","authors":"Junghyun Kim, Jaeyong Shin, Man S Kim, Jae Hoon Moon","doi":"10.1210/clinem/dgae751","DOIUrl":"https://doi.org/10.1210/clinem/dgae751","url":null,"abstract":"<p><strong>Background: </strong>Wearable devices can now leverage the established correlation between thyroid function and heart rate to monitor thyroid function alongside exercise levels and heart rate. The objective was to assess the cost-effectiveness of introducing a wearable/mobile-based thyroid function digital monitoring solution for the management of hypothyroidism compared to the conventional management approach.</p><p><strong>Methods: </strong>A decision-analytic Markov state-transition simulation model employed for utilizing a simulated cohort of 10,000 40-year-old patients with hypothyroidism to estimate costs and health outcomes. Cost-effectiveness from the healthcare sector perspective was evaluated using a 4.5% annual discount rate and the costs adjusted to 2022 levels, and lifetime outcomes were presented through incremental cost-effectiveness 49 ratios (ICERs). Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results.</p><p><strong>Results: </strong>The digital monitoring solution supported group yielded an additional 0.65 QALYs with an incremental cost of $11700.87, resulting in an ICER value of $17988.97 per QALY gained. Digital-powered software could be an optimal strategy in 99% of iterations against willingness-to-pay thresholds of $32,255/QALY gained. The ICER was most sensitive to the annual cost of a digital monitoring solution for hypothyroidism.</p><p><strong>Conclusion: </strong>The incorporation of the digital monitoring solution has demonstrated positive cost-effectiveness in hypothyroidism management when compared to the standard care. The cost of the digital monitoring solution and its sensitivity are key factors in determining cost-effectiveness. Striking a balance among the cost of digital monitoring support, the precision of hormonal level monitoring, and its effectiveness for the specific group of hypothyroid patients in real-world clinical practice is essential.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512181","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":"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":"https://doi.org/10.1210/clinem/dgae748","url":null,"abstract":"<p><strong>Context: </strong>1-hour post-load glucose (1h-PG) detects dysglycemia-related disorders more effectively than traditional glycemic parameters. Hyperglycemia accelerates aging, 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 non-diabetic and diabetic populations.</p><p><strong>Results: </strong>The cross-sectional study included 715 participants. Only 1h-PG was significantly negatively associated with RTL in both non-diabetic (β = -0.106, 95%CI -0.068 to -0.007, P = 0.017) (odds ratio [OR] = 1.151, 95% CI 1.069 to 1.239, P = 0.005) and diabetic (β = -0.222, 95%CI -0.032 to -0.007, P = 0.002) (OR = 1.144, 95% CI 1.041 to 1.258, P = 0.035) populations. The longitudinal study recruited 437 populations and 112 remained in 7-years follow-up. 1h-PG was associated with telomere shortening in the non-diabetic group (β = -0.314, 95%CI -0.276 to -0.032, P = 0.016) (OR = 2.659, 95% CI 1.158 to 6.274, P = 0.021). 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>Conclusions: </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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.","authors":"Yu Lei, Anna Wiik, Margery A Connelly, Linnea Lindberg, Daniel P Andersson, Stefan Arver, Thomas Gustafsson, Uwe J F Tietge","doi":"10.1210/clinem/dgae745","DOIUrl":"https://doi.org/10.1210/clinem/dgae745","url":null,"abstract":"<p><strong>Background: </strong>While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.</p><p><strong>Methods: </strong>17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness (cIMT) and arterial stiffness, lipoproteins and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and HDL-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the impact of sex hormones, comparisons of genetic XX and XY individuals at T1 the impact of sex chromosomes.</p><p><strong>Results: </strong>Vascular function was comparable at T12 and T0; systolic blood pressure increased in transmen (p=0.002). Transmen developed a pro-atherogenic lipoprotein profile, estrogen treatment in transwomen tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transmen (p=0.025), with opposite changes in transwomen (p=0.002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (p=0.002). CEC decreased in transwomen (p<0.01), while remaining unchanged in transmen. However, in both groups the strong positive association of apoA-I with cholesterol efflux observed at T0 was lost at T12.</p><p><strong>Conclusions: </strong>The results are consistent with increased cardiometabolic risk in transmen, while transwomen show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have less intrinsic effects. XY individuals and transmen display an increased apparent diabetes risk. Further research of cardiometabolic risk is needed for transgender individuals.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512179","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":"Effects of a Carbohydrate-Restricted Diet on β-Cell Response in Adults With Type 2 Diabetes.","authors":"Barbara A Gower, Amy M Goss, Marian L Yurchishin, Sarah E Deemer, Bhuvana Sunil, William T Garvey","doi":"10.1210/clinem/dgae670","DOIUrl":"https://doi.org/10.1210/clinem/dgae670","url":null,"abstract":"<p><strong>Context: </strong>β-Cell response to glucose is compromised in individuals with type 2 diabetes (T2D), possibly due in part to excessive carbohydrate consumption.</p><p><strong>Objective: </strong>This study was conducted to determine if a eucaloric carbohydrate-restricted (CR) diet (∼9% energy from carbohydrate, 65% energy from fat), compared to a eucaloric higher carbohydrate (HC) diet (∼55% energy from carbohydrate, 20% energy from fat), would improve β-cell response to glucose in participants with T2D.</p><p><strong>Methods: </strong>Participants were 57 African American and European American adults with T2D not using insulin. Medications were discontinued 1 to 2 weeks prior to baseline testing. A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide response to glucose at baseline and after 12 weeks of controlled diet therapy (all food provided). An oral glucose tolerance test (OGTT) was used to assess the disposition index (DI).</p><p><strong>Results: </strong>At 12 weeks, a statistically significant effect of diet was observed on acute C-peptide response (2-fold greater with the CR diet; P < .01). For maximal C-peptide, a significant effect of diet was observed (22% greater with the CR diet; P < .05), as was a significant diet-by-race interaction (P < .05), indicating that the diet effect was specific to European Americans (48% greater with the CR diet; P < .01). OGTT results showed a significant effect of diet on DI at 12 weeks (32% greater with the CR diet; P < .05).</p><p><strong>Conclusion: </strong>These results suggest that a eucaloric CR diet has beneficial effects on β-cell function in patients with mild T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512182","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}