Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Machine Learning: A Multicenter Study on Predicting Lateral Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma.","authors":"Jing Zhou, Daxue Li, Jiahui Ren, Chun Huang, Shiying Yang, Mingyao Chen, Zhaoyu Wan, Jinhang He, Yuchen Zhuang, Song Xue, Lin Chun, Xinliang Su","doi":"10.1210/clinem/dgaf070","DOIUrl":"10.1210/clinem/dgaf070","url":null,"abstract":"<p><strong>Background: </strong>The necessity of prophylactic lateral neck dissection for cN0 papillary thyroid carcinoma (PTC) remains debated. This study aimed to compare traditional nomograms with machine learning (ML) models for predicting ipsilateral lateral and level II, III, and IV lymph node metastasis (LNM).</p><p><strong>Methods: </strong>Data from 1616 PTC patients diagnosed via fine-needle aspiration biopsy from hospital A were split into training and testing sets (7:3). Two hundred forty-three patients from hospital B served as a validation set. Four dependent variables-ipsilateral lateral and level II, III, and IV LNM-were analyzed. Eight ML models [logistic regression, decision tree, random forest (RF), gradient boosting, support vector machine, K-nearest neighbor, Gaussian naive Bayes, neural networks] were developed and validated using 10-fold cross-validation and grid search hyperparameter tuning. Models were assessed using 11 metrics including accuracy, area under the curve (AUC), specificity, and sensitivity. The best was compared with nomograms using the probability-based ranking model approach (PMRA).</p><p><strong>Results: </strong>RF outperformed other approaches achieving accuracy, AUC, specificity, and sensitivity of 0.773/0.728, 0.858/0.799, 0.984/0.935, 0.757/0.807 in the testing/validation sets, respectively, for ipsilateral LLNM. A streamlined model based on the top 10 contributing features that includes ipsilateral central lymph node metastasis rate, extrathyroidal extension, and ipsilateral central lymph node metastasis number retained strong performance and clearly surpassed a traditional nomogram approach based on multiple metrics and PMRA analysis. Similar results were obtained for the other dependent variables, with the RF models relying on distinct but overlapping sets of features. Clinical tool implementation is facilitated via a web-based calculator for each of the 4 dependent variables.</p><p><strong>Conclusion: </strong>ML, especially RF, reliably predicts lateral LNM in cN0 PTC patients, outperforming traditional nomograms.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2762-2776"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374811","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":"Dysbetalipoproteinemia: Focus on a Neglected Lipid Disorder.","authors":"Amanda J Berberich, Robert A Hegele","doi":"10.1210/clinem/dgae804","DOIUrl":"10.1210/clinem/dgae804","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3528-e3529"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631747","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":"Sex Differences in the Association Between Thyroid Hormone Sensitivity and Cardiovascular-Kidney-Metabolic Syndrome.","authors":"Lanxuan Jiang, Liyuan Zhou, Jia Liu, Ying Wang, Guang Wang","doi":"10.1210/clinem/dgaf059","DOIUrl":"10.1210/clinem/dgaf059","url":null,"abstract":"<p><strong>Background: </strong>The relationship between thyroid hormone sensitivity and cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. This study aims to investigate the association between thyroid hormone sensitivity and the early-stage of CKM syndrome, with a specific focus on the moderating effects of sex and age.</p><p><strong>Methods: </strong>A total of 8391 euthyroid participants were enrolled in this cross-sectional study. Data on metabolic parameters and thyroid hormone levels were collected. Thyroid hormone sensitivity indices-thyroid feedback quantile index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI), and free T3 to free T4 ratio were calculated. Logistic regression models and restricted cubic spline regression (RCS) were used to analyze the association between thyroid hormone sensitivity and stage 2 of CKM syndrome stratified by sex and age.</p><p><strong>Results: </strong>In men, the higher TFQI, TSHI, and TT4RI values were significantly associated with increased risks of stage 2 of CKM syndrome. In women, these associations were weaker but still present, particularly for TSHI. RCS analysis also showed that the risk of CKM syndrome tended to increase with decreasing thyroid hormone sensitivity in men. However, these associations in women were not as significant as in men. Age-stratified analysis revealed that older men (>50 years) showed a stronger correlation between thyroid hormone sensitivity and CKM syndrome compared to women.</p><p><strong>Conclusion: </strong>This study demonstrated that impaired thyroid hormone sensitivity was significantly associated with the early-stage of CKM syndrome, particularly in older men. These findings provide the evidence of the importance of thyroid hormone sensitivity in CKM syndrome, especially in men over the age of 50.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3303-e3312"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124076","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":"Approach to the Patient: Hirsutism.","authors":"Ricardo Azziz, Mina Amiri, Fernando Bril, Anju E Joham, Fahrettin Kelestimur, Sasha Ottey, Larisa Suturina, Chau Thien Tay, Helena Teede, Bulent O Yildiz, Xiaomiao Zhao","doi":"10.1210/clinem/dgaf226","DOIUrl":"10.1210/clinem/dgaf226","url":null,"abstract":"<p><p>Hirsutism affects approximately 10% of women globally, with substantial economic and quality of life effect. Facial and body terminal hair growth in a male-like pattern is determined by a number of factors, including circulating androgens, and tissue androgen receptor, 5α-reductase, 3α- and 17β-hydroxysteroid dehydrogenase, and ornithine decarboxylase content. The presence of hirsutism is usually determined by the modified Ferriman-Gallwey (mFG) visual scale, assessing the amount of terminal hair at 9 body sites (upper lip, chin, chest, upper and lower back, upper and lower abdomen, upper arms, and thighs). Specific diagnostic cutoffs vary somewhat by ethnicity, although hirsutism is usually defined by an mFG score greater than 4 to 6. Hirsutism is a sign of polycystic ovary syndrome in 80% to 90% of affected women, idiopathic hirsutism in 5% to 10%, and, depending on ethnicity, 21-hydroxylase-deficient nonclassic adrenal hyperplasia in 1% to 10%. Rarer causes include androgen-secreting neoplasms, iatrogenic/drug-induced, acromegaly, Cushing syndrome, syndromes of severe insulin resistance/lipodystrophy, ovarian hyperthecosis, and chronic skin irritation. The choice of treatment for hirsutism depends on the severity of symptoms, the patient's reproductive goals, and the underlying cause. Clinicians should not underestimate the degree of patient distress caused by hirsutism. Further, women who complain of excess unwanted hair growth should be evaluated for underlying causes, regardless of the degree to which hirsutism is observable on examination. Management options include medical therapies, such as combined oral contraceptive pills and antiandrogens, and mechanical methods of hair removal. The most effective therapeutic strategy will involve a combination of these modalities, with shared decision-making a key driver.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3503-e3519"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812825","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":"Longitudinal Association of Statin Treatment With Insulin Sensitivity and Beta-Cell Function in the PROMISE Cohort.","authors":"Kira Zhi Hua Lai, Stewart B Harris, Ravi Retnakaran, Anthony J G Hanley, Ute I Schwarz","doi":"10.1210/clinem/dgaf031","DOIUrl":"10.1210/clinem/dgaf031","url":null,"abstract":"<p><strong>Context: </strong>Statin treatment lowers low-density lipoprotein (LDL) cholesterol, thereby reducing cardiovascular risk. Meta-analyses of clinical trials report a higher risk of new-onset type 2 diabetes with statins. Current clinical evidence regarding effects of statins on insulin sensitivity and beta-cell function is limited.</p><p><strong>Objective: </strong>We examined the effects of statin treatment on longitudinal changes in early-risk phenotypes for type 2 diabetes.</p><p><strong>Methods: </strong>The PROMISE cohort is a longitudinal study of adults at risk for type 2 diabetes. Data from baseline and 3 follow-up visits over 9 years were used to estimate insulin sensitivity (insulin sensitivity index, homeostatic model assessment for insulin sensitivity) and beta-cell function (insulinogenic index/homeostatic model assessment for insulin resistance, insulin secretion sensitivity index-2). Statin use was self-reported. Associations of statins with changes in metabolic markers were determined through generalized estimating equations.</p><p><strong>Results: </strong>Over 9 years, 169 of 498 participants (aged 50 years, 74% female) received a statin, predominantly rosuvastatin and atorvastatin. Compared to those with no statin treatment, statin users had lower insulin sensitivity (5.32%-6.36%) and beta-cell function (4.93%-7.59%) (P < .001), adjusting for metabolic risk factors. Rosuvastatin was associated with decreased insulin sensitivity and beta-cell function, while atorvastatin showed moderate inverse association with beta-cell function and insulin sensitivity. In female participants, statins reduced insulin sensitivity and beta-cell function, while in male participants only beta-cell function was altered.</p><p><strong>Conclusion: </strong>Statin treatment was associated with lowered insulin sensitivity and beta-cell function with potential differential effects among statin agents and the sexes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3442-e3452"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015404","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":"The Role of the Parametric Thyroid Feedback Quantile Index in Cardiovascular Risk Evaluation Among Euthyroid Koreans.","authors":"Hun Jee Choe, Yun Mi Choi, Yeonjung Ha, Jinseob Kim, Minhyuk Kim, Ho Jin Cha, Jiwoo Lee, Mi Kyung Kwak, Eun-Gyoung Hong","doi":"10.1210/clinem/dgaf046","DOIUrl":"10.1210/clinem/dgaf046","url":null,"abstract":"<p><strong>Context: </strong>Thyroid hormones play a crucial role in metabolic regulation and maintaining cardiovascular homeostasis. The Parametric Thyroid Feedback Quantile-based Index (PTFQI) assesses central thyroid hormone sensitivity by standardizing the inverse relationship between free thyroxine (T4) and TSH.</p><p><strong>Objective: </strong>To investigate the relationship between PTFQI and cardiovascular risk in the euthyroid Korean population.</p><p><strong>Methods: </strong>Using data from the 2013 through 2015 Korea National Health and Nutrition Examination Survey, we included 5160 euthyroid adults aged 18 to 80 years who were not previously diagnosed with cardiovascular or thyroid disease. Cardiovascular risk was evaluated using the Predicting Risk of Cardiovascular Disease EVENTs and pooled cohort equations scores.</p><p><strong>Results: </strong>Stratification by PTFQI quartiles revealed an inverse relationship between PTFQI and cardiovascular risk. Higher PTFQI quartiles were associated with lower risks of cardiovascular disease (adjusted odds ratio [aOR], -0.55; 95% CI, -.92 to -.18), atherosclerotic cardiovascular disease (aOR, -0.31; 95% CI, -.53 to -.08), heart failure (aOR, -0.26; 95% CI, -.47 to -.05), coronary heart disease (aOR, -0.15; 95% CI, -.28 to -.02), and ischemic stroke (aOR, -0.18; 95% CI, -.30 to -.06). These associations persisted after adjusting for thyroid peroxidase antibodies, iodine intake, alcohol consumption, physical activity, and income level. The pooled cohort equations score demonstrated a strong correlation with the Predicting Risk of cardiovascular disease EVENTs score.</p><p><strong>Conclusion: </strong>The PTFQI inversely correlated with cardiovascular risk among euthyroid Koreans, indicating that reduced central sensitivity to thyroid hormone is associated with lower cardiovascular risk. These results underscore the importance of considering population-specific thyroid function parameters in cardiovascular risk assessment.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3401-e3409"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025718","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":"Construction of a Simplified Bone Age Assessment Model in Chinese Children Aged 3 to 18 Years.","authors":"Hua-Hong Wu, Ya-Qin Zhang, Cheng-Dong Yu, Yang Li, Wen Shu, Tao Li, Gui-Min Huang, Dong-Qing Hou, Fang-Fang Chen, Jun-Ting Liu, Shao-Li Li, Xin-Nan Zong","doi":"10.1210/clinem/dgaf022","DOIUrl":"10.1210/clinem/dgaf022","url":null,"abstract":"<p><strong>Context: </strong>Bone age assessment (BAA) is critical for pediatric endocrinology. Traditional methods are complex and time-consuming, and current computer-aided systems have made progress but still lacking in robustness.</p><p><strong>Objective: </strong>Develop simplified BAA methods to aid pediatricians in quick clinical assessments.</p><p><strong>Design: </strong>Overall, 5551 left-hand X-ray images were collected from a cross-sectional survey in 2022 and 2023. Bone age (BA) was assessed using the Tanner-Whitehouse 3-China/radius-ulna-short bone method. The linear regression models were constructed with BA as the dependent variable and 13 radius-ulna-short bone bones' grades as independent variables.</p><p><strong>Setting: </strong>A cross-sectional survey in Beijing, China.</p><p><strong>Participants: </strong>A total of 5551 children aged 3 to 18 years.</p><p><strong>Main outcome measures: </strong>Model accuracy was evaluated by R², residuals, and root mean square error, and BA with an error margin ≤0.5 years.</p><p><strong>Results: </strong>When bone grades were consistent, a single or few bones may serve as proxies for BA, such as metacarpals and phalanges reaching grade 6, the BA for boys and girls were 13.0 to 13.5 years and 10.9 to 11.5 years, respectively. When bone grades were inconsistent, regression models were needed. Comparatively, the 3-bone models have advantages and are proposed for clinically simplified BAA. The simplified 3-bone model (radius, ulna, and metacarpal I) yielded an R² > 0.94 and a root mean square error < 0.5 years. When considering puberty stages, specific bone combination models can further improve assessment accuracy.</p><p><strong>Conclusion: </strong>These 3-bone models could be useful for rapid BAA, with improved accuracy when puberty stages is included. Further validation is warranted to test their robustness across populations and scenarios.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2926-2937"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985306","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":"PI3K/AKT/mTOR Activation Is Associated With Malignant Severity and Poorer Prognosis in Parathyroid Carcinomas.","authors":"Jia-Xi Song, Yong-Qiang Dong, Ru-Lai Han, Jing Xie, An-Ying Zhu, Xi Chen, Yu-Ying Yang, Chun-Xiang Sheng, Tao Jiang, Hong-Yan Zhao, Bei Tao, Guang Ning, Wei-Qing Wang, Li-Hao Sun, Lei Ye, Xiu-Bo Lu, Jian-Min Liu","doi":"10.1210/clinem/dgaf042","DOIUrl":"10.1210/clinem/dgaf042","url":null,"abstract":"<p><strong>Context and objective: </strong>Parathyroid carcinoma (PCa) is a rare endocrine neoplasm known for its high recurrence. The specific molecular properties influencing the prognosis of PCa remain largely elusive. The present study was designed to explore the significance of PI3K/AKT/mTOR activation in PCa.</p><p><strong>Methods: </strong>Over a 10-year period, 64 PCa patients were recruited from dual centers. We analyzed mechanistic target of rapamycin complex I (mTORC1) activity in 64 PCa patients and 29 controls, comprising atypical parathyroid tumor (APT), parathyroid adenoma (PAd), and normal parathyroid tissues. A panel of selected genes targeting the PI3K/AKT/mTOR pathway (PIK3CA, PTEN, MTOR, TSC1, and TSC2) and CDC73 was performed in 66 available tumor tissues from 64 patients with PCa. Follow-up lasted up to 117 months.</p><p><strong>Results: </strong>There was intertumoral heterogeneity in mTORC1 activity in parathyroid tumors. Notably, we observed significantly elevated mTORC1 activity in PCa patients compared with controls, as assessed by immunohistochemical staining of tissue sections. Further analysis showed that 48.5% of PCa tumors were classified as \"high mTORC1\" (above the predefined threshold), while only 22.7% of tumors in the PAd/APT group met this criterion. Additionally, we detected PI3K/AKT/mTOR variants in 16/66 (24.2%) PCa samples, with the majority lacking CDC73 variants. Higher mTORC1 activity was noted in PCa with PI3K/AKT/mTOR variants than in those without. Compared with those without any targeted variants, the PI3K/AKT/mTOR-mutated group presented higher levels of serum PTH, alkaline phosphatase, and creatinine and was associated with significantly lower disease-free survival (DFS) and overall survival (OS) (DFS, P < .001; OS, P < .01).</p><p><strong>Conclusion: </strong>Our findings highlight that the activation of the PI3K/AKT/mTOR pathyway in PCa patients suggests their degree of malignancy, possibly leading to poor outcomes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2892-2902"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015441","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":"Predicting Preeclampsia in Gestational Diabetes Mellitus Using the sFlt-1/PlGF Ratio.","authors":"Sarah Brittany Noonan, Shaun Patrick Brennecke, Gabriel Davis Jones","doi":"10.1210/clinem/dgaf069","DOIUrl":"10.1210/clinem/dgaf069","url":null,"abstract":"<p><strong>Context: </strong>The soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio blood test can aid the prediction of preeclampsia (PE) in advance of a clinical diagnosis. Gestational diabetes mellitus (GDM) predisposes to PE, but may influence levels of these biomarkers independently of PE.</p><p><strong>Objective: </strong>To determine whether the sFlt-1/PlGF ratio retains its clinical utility to predict PE in patients with GDM.</p><p><strong>Methods: </strong>Retrospective analysis of sFlt-1/PlGF ratio and associated clinical outcome data acquired between September 2016 and September 2022, at the Royal Women's Hospital, Melbourne, Australia. 1416 sFlt-1/PlGF ratio results from pregnant women with and without GDM, and with and without PE were analysed. The main outcome measures were sFlt-1, PlGF and sFlt-1/PlGF ratio test results in relation to PE and GDM.</p><p><strong>Results: </strong>There were no significant differences in the area under the curve (AUC), specificity, sensitivity, positive predictive value, or negative predictive value (NPV) between the PE + No GDM and PE + GDM groups in both the 0 to 7 and the 8 to 14 days before delivery categories. In the 0- to 7-day category the PE + No GDM group had an AUC of 0.82 (95% CI 0.79-0.87), sensitivity of 85.3% (95% CI 80.8-89.1%) and NPV of 92.7% (95% CI 90.5-94.5%), and the PE + GDM group had an AUC of 0.87 (95% CI 0.82-0.93), sensitivity of 89.4% (95% CI 76.9-96.5%), and NPV of 94.8% (95% CI 88.7-97.7%).</p><p><strong>Conclusion: </strong>The results of this investigation indicate that although GDM may lead to changes in the sFlt-1/PlGF ratio, the sFlt-1/PlGF ratio test retains its clinical utility in predicting PE onset.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3343-e3352"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191138","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":"Role of Hepatic Glycogen on Nocturnal Gluconeogenesis in Type 2 Diabetes Mellitus.","authors":"Uma S Unni, Fernando Bril, John P Mugler, Rickey E Carter, Ananda Basu, Rita Basu","doi":"10.1210/clinem/dgaf044","DOIUrl":"10.1210/clinem/dgaf044","url":null,"abstract":"<p><strong>Context: </strong>Higher gluconeogenesis (GNG) contributes to higher nocturnal endogenous glucose production (EGP) in type 2 diabetes (T2D). Studies using 13C magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects with no diabetes (ND).</p><p><strong>Objective: </strong>We determined the role of glycogen loading (GL) vs nonglycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D.</p><p><strong>Methods: </strong>In total, 14 subjects with T2D and 15 matched subjects with ND were studied on 2 occasions, with GL (60% carbohydrate) vs NGL (40% carbohydrate) isocaloric meals for 3 days, in random order in the overnight state. [6,6-2H2] glucose was infused to measure EGP, deuterium labelled water was used to measure GNG, and 13C MRS scans were performed in fed and fasted states to measure hepatic glycogen content.</p><p><strong>Results: </strong>Hepatic glycogen content and nocturnal EGP were higher (P < .05) in GL vs NGL in both cohorts. The % GNG to EGP averaged ∼50% in subjects with ND throughout the night after both meals. In contrast, % GNG to nocturnal EGP in T2D was lower with GL vs NGL and matched the pattern observed in subjects with ND with GL lowering overnight rates of GNG in subjects with T2D.</p><p><strong>Conclusion: </strong>Selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning fasting hyperglycemia and hepatic insulin resistance in people with T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2790-2799"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191140","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}