Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Progressive Impairment of Prepubertal Growth in Children With APECED.","authors":"Viivi Saari, Venla Alanko, Elina Holopainen, Outi Mäkitie, Saila Laakso","doi":"10.1210/clinem/dgae209","DOIUrl":"10.1210/clinem/dgae209","url":null,"abstract":"<p><strong>Context: </strong>Subjects with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) have subnormal adult height. There are several potential APECED-related risk factors for suboptimal height attainment during childhood.</p><p><strong>Objective: </strong>To determine the growth patterns in children with APECED.</p><p><strong>Methods: </strong>This retrospective longitudinal study included 59 children with APECED from the Finnish national APECED cohort and assessed length/height and weight z-scores from birth to the end of prepuberty.</p><p><strong>Results: </strong>Collectively, 59 children (30 [51%] girls) were included. Their median birth weight z-score (-0.60) was below the population average; 12 (20%) patients were born small for gestational age. Height attainment progressively declined from birth until the end of prepuberty (z-score -1.95), whereas weight-for-height z-score did not (+0.26). Of the 59 patients, 38 (64%) had all height z-scores below 0 during prepuberty, and 7 (12%) had z-scores below -2.0. Age at the end of prepuberty, number of APECED manifestations, duration of glucocorticoid treatment, and growth hormone deficiency correlated negatively with height z-score at the end of prepuberty (P < .0001; P = .041; P = .013; P = .034, respectively).</p><p><strong>Conclusion: </strong>Children with APECED had a progressive growth impairment from birth through prepuberty. Multiple predisposing risk factors were recognized, including disease severity and growth hormone deficiency. Timely interventions are needed to ensure optimal height attainment and new treatment options need to be developed.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e257-e265"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869409","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":"Barriers to the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.","authors":"Kelsey B Eitel, Patricia Y Fechner","doi":"10.1210/clinem/dgae710","DOIUrl":"10.1210/clinem/dgae710","url":null,"abstract":"<p><p>Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare genetic condition that requires lifelong management from birth. Individuals with CAH and their families often face structural barriers to obtaining comprehensive care and treatment, including limited access to appropriate newborn screening, comprehensive care centers, and medications. Social and cultural barriers to care may include stigmatization, discrimination, and adverse medical experiences. At the individual and family level, comprehensive care may be affected by education, finances, health-care coverage, geographic location, and lack of social supports. These barriers are often further magnified for individuals living in underresourced countries. Inadequate access to comprehensive care and medications increases the risk of life-threatening adrenal crisis and disease-related comorbidities. This review article examines the current structural, sociocultural, and individual barriers that individuals with CAH and their families may face when managing their condition throughout their lifetime.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":"110 Supplement_1","pages":"S67-S73"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015494","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":"Altered expression of aromatase and estrogen receptors in adipose tissue from men with obesity or type 2 diabetes.","authors":"Fozia Ahmed, Susanne Hetty, Rutger Laterveer, Ece Busra Surucu, Argyri Mathioudaki, Edvin Hornbrinck, Vagia Patsoukaki, Johan Olausson, Magnus Sundbom, Maria K Svensson, Maria J Pereira, Jan W Eriksson","doi":"10.1210/clinem/dgaf038","DOIUrl":"https://doi.org/10.1210/clinem/dgaf038","url":null,"abstract":"<p><strong>Objective: </strong>Obesity and insulin resistance in men are linked to decreased testosterone and increased estradiol (E2) levels. Aromatase (ARO) converts testosterone into E2, and this occurs mainly in adipose tissue in men. E2 acts through estrogen receptors ESR1 and ESR2, and they potentially affect development of type 2 diabetes (T2D). This study explored alterations in ARO, ESR1 and ESR2 in men with obesity or T2D.</p><p><strong>Methods: </strong>Subcutaneous adipose tissue (SAT) from men with or without obesity or T2D was analyzed for ARO, ESR1, and ESR2 gene and protein expression. Data were compared across groups and correlated with markers of obesity, glycaemia, insulin resistance, and sex hormones. Moreover, SAT was incubated with E2 or testosterone for ex vivo glucose uptake measurements.</p><p><strong>Results: </strong>Aromatase ARO levels were higher in SAT from men with obesity compared to non-obese men, and gene expression correlated positively with adiposity, hyperglycaemia and insulin resistance. No association was found between ARO and circulating E2. Men with obesity had lower levels of ESR1 and ESR1:ESR2 ratio, but not ESR2. ESR1 gene expression in SAT correlated negatively with adiposity and insulin resistance markers as well as with ARO expression, and tended to be lower in men with T2D. E2 reduced insulin-stimulated glucose uptake, while testosterone increased basal glucose uptake in adipocytes.</p><p><strong>Conclusion: </strong>Elevated ARO in SAT was found in obese men, and this was linked to insulin resistance and glycaemia, supporting that local estrogen production contributes to metabolic dysregulation. ESR1 was reduced in men with T2D and was linked to adiposity and insulin resistance. Taken together, high ARO and low ESR1 expression in SAT in obese men may contribute to insulin resistance and T2D development.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015379","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 Bone Mineral Density as a Risk Factor for Liver Cirrhosis.","authors":"Xiaowen Zhang, Ka-Shing Cheung, Lung-Yi Mak, Kathryn C B Tan, Annie W C Kung, Ian Chi-Kei Wong, Ching-Lung Cheung","doi":"10.1210/clinem/dgae223","DOIUrl":"10.1210/clinem/dgae223","url":null,"abstract":"<p><strong>Context: </strong>Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown.</p><p><strong>Objective: </strong>This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS).</p><p><strong>Methods: </strong>BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7752 participants by dual-energy x-ray absorptiometry (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CI.</p><p><strong>Results: </strong>With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip, and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56; 95% CI, 0.39-0.82; total hip: HR 0.60; 95% CI, 0.44-0.82; trochanter: HR 0.63; 95% CI, 0.46-0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results.</p><p><strong>Conclusion: </strong>Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e276-e282"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871625","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":"Adult Height in Transgender Youth Who Receive GnRH Analogues Followed by Gender-Affirming Hormone Therapy.","authors":"Ada S Cheung","doi":"10.1210/clinem/dgae397","DOIUrl":"10.1210/clinem/dgae397","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e538-e539"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307320","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":"Endogenous Estrogens and Brain Activation During Verbal Memory Encoding and Recognition in the Postmenopause.","authors":"Rachel A Schroeder, Rebecca C Thurston, Minjie Wu, Howard J Aizenstein, Carol A Derby, Pauline M Maki","doi":"10.1210/clinem/dgae467","DOIUrl":"10.1210/clinem/dgae467","url":null,"abstract":"<p><strong>Context: </strong>Changes in verbal memory have been reliably reported across the menopause transition. To understand the role of endogenous estrogens in verbal memory performance, this study assessed the associations of endogenous estradiol and estrone with brain network connectivity during a verbal memory fMRI task.</p><p><strong>Objective: </strong>Determine associations of endogenous estrogens with memory systems in the postmenopausal brain and evaluate clinical significance.</p><p><strong>Methods: </strong>In the MsBrain cohort (n = 199, mean age 59.3 ± 3.9 years, 83.9% White), we examined the cross-sectional association of serum estradiol (E2) and estrone (E1), measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), during a functional magnetic resonance imaging (fMRI) task of word encoding and recognition. To characterize the clinical significance of those associations, we examined the magnitude of activation in relation to a neuropsychological measures of memory and affect.</p><p><strong>Results: </strong>Endogenous E2 was positively associated with activation in temporal and frontal cortices during encoding and negatively associated with one prefrontal region during recognition (P < .05). Activation in the left inferior frontal gyrus was associated with memory performance (β [SE] = 0.004 [0.002]; P < .05), and anxiety (β [SE] = -0.100 [0.050]; P < .05). The left middle frontal gyrus was associated with memory performance (β [SE] = 0.006 [0.002]; P < .01), depression, and anxiety. The left superior temporal gyrus (STG) was associated with depression (β [SE] = -0.083 [0.036]; P < .05) and anxiety (β [SE] = -0.134 [0.058]; P < .05). E1 was positively associated with activation in a range of brain areas including bilateral STG and right superior frontal gyrus during encoding (P < .05). Activation of the left insula and precentral gyrus were associated with symptoms of depression and anxiety. None related to memory.</p><p><strong>Conclusion: </strong>The function of brain areas critical to memory performance varies with estrogen levels in the postmenopause, even though those levels are low. Higher levels of E2 may facilitate memory performance through enhanced function of temporal and frontal cortices during encoding of verbal material.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"452-461"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724963","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":"Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (URRAH Project).","authors":"Lanfranco D'Elia, Maria Masulli, Agostino Virdis, Edoardo Casiglia, Valerie Tikhonoff, Fabio Angeli, Carlo Maria Barbagallo, Michele Bombelli, Federica Cappelli, Rosario Cianci, Michele Ciccarelli, Arrigo F G Cicero, Massimo Cirillo, Pietro Cirillo, Raffaella Dell'Oro, Giovambattista Desideri, Claudio Ferri, Loreto Gesualdo, Cristina Giannattasio, Guido Grassi, Guido Iaccarino, Luciano Lippa, Francesca Mallamaci, Alessandro Maloberti, Stefano Masi, Alberto Mazza, Alessandro Mengozzi, Maria Lorenza Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Gianpaolo Reboldi, Giulia Rivasi, Elisa Russo, Massimo Salvetti, Giuliano Tocci, Andrea Ungar, Paolo Verdecchia, Francesca Viazzi, Massimo Volpe, Claudio Borghi, Ferruccio Galletti","doi":"10.1210/clinem/dgae170","DOIUrl":"10.1210/clinem/dgae170","url":null,"abstract":"<p><strong>Purpose: </strong>Recently, a novel index [the triglyceride-glucose (TyG) index]) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk.</p><p><strong>Methods: </strong>The analysis included 16 649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis.</p><p><strong>Results: </strong>During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only 1 of the 2 factors.</p><p><strong>Conclusion: </strong>The results of this study indicate that these TyG (a low-cost and simple, noninvasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e470-e477"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121290","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 Evaluation of Reproductive Endocrine Function in Men With ACTH-Dependent Cushing Syndrome.","authors":"Skand Shekhar, Raven N McGlotten, Gordon B Cutler, Matthew J Crowley, Carl F Pieper, Lynnette K Nieman, Janet E Hall","doi":"10.1210/clinem/dgae497","DOIUrl":"10.1210/clinem/dgae497","url":null,"abstract":"<p><strong>Context: </strong>Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences.</p><p><strong>Objective: </strong>This work aimed to determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause.</p><p><strong>Methods: </strong>Post hoc analyses of prospective cohort studies were conducted at a clinical research center. Study participants were men with adrenocorticotropic hormone (ACTH)-dependent CS: cohort 1 (C1) (n = 8, age 32.5 ± 12 years; studied 1985-1989) and cohort 2 (C2) (n = 44, 42.7 ± 15.1 years; studied 1989-2021). Interventions included the following: C1: every 20-minute blood sampling for 24 hours before and 1 to 40 months after surgical cure. Three individuals underwent gonadotropin-releasing hormone (GnRH) stimulation tests pre and post surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post cure. Main outcome measures included the following: C1: LH, FSH, LH pulse frequency, and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, free thyroxine, 3,5,3'-triiodothyronine, thyrotropin, and urine free cortisol (UFC) levels and frequency of hypogonadism pre and post surgery.</p><p><strong>Results: </strong>C1: mean LH and LH pulse frequency increased after surgery (P < .05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and sex hormone-binding globulin increased at 6 and 12 M post surgery, but hypogonadism persisted in 51% at 6 M and in 26% at 12 M.</p><p><strong>Conclusion: </strong>Hypogonadism in men with CS is widely prevalent but reversible in approximately 75% of patients 1 year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"471-479"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629211","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":"Pleiotropic Effects of an eQTL in the CELSR2/PSRC1/SORT1 Cluster That Associates With LDL-C and Resting Metabolic Rate.","authors":"Khushdeep Bandesh, Kendrick Freeland, Michael Traurig, Robert L Hanson, Clifton Bogardus, Paolo Piaggi, Leslie J Baier","doi":"10.1210/clinem/dgae498","DOIUrl":"10.1210/clinem/dgae498","url":null,"abstract":"<p><strong>Context: </strong>The locus CELSR2-PSRC1-SORT1, a primary genetic signal for lipids, has recently been implicated in different metabolic processes. Our investigation identified its association with energy metabolism.</p><p><strong>Objective: </strong>This work aimed to determine biological mechanisms that govern diverse functions of this locus.</p><p><strong>Methods: </strong>Genotypes for 491 265 variants in 7000 clinically characterized American Indians were previously determined using a custom-designed array specific for this longitudinally studied American Indian population. Among the genotyped individuals, 5205 had measures of fasting lipid levels and 509 had measures of resting metabolic rate (RMR) and substrate oxidation rate assessed through indirect calorimetry. A genome-wide association study (GWAS) for low-density lipoprotein cholesterol (LDL-C) levels identified a variant in CELSR2, and the molecular effect of this variant on gene expression was assessed in skeletal muscle biopsies from 207 participants, followed by functional validation in mouse myoblasts using a luciferase assay.</p><p><strong>Results: </strong>A GWAS in American Indians identified rs12740374 in CELSR2 as the top signal for LDL-C levels (P = 1 × 10-22); further analysis of this variant identified an unexpected correlation with reduced RMR (effect = -44.3 kcal/day/minor-allele) and carbohydrate oxidation rate (effect = -5.21 mg/hour/kg-EMBS). Tagged variants showed a distinct linkage disequilibrium architecture in American Indians, highlighting a potential functional variant, rs6670347 (minor-allele frequency = 0.20). Positioned in the glucocorticoid receptor's core binding motif, rs6670347 is part of a skeletal muscle-specific enhancer. Human skeletal muscle transcriptome analysis showed CELSR2 as the most differentially expressed gene (P = 1.9 × 10-7), with the RMR-lowering minor allele elevating gene expression. Experiments in mouse myoblasts confirmed enhancer-based regulation of CELSR2 expression, dependent on glucocorticoids. Rs6670347 was also associated with increased oxidative phosphorylation gene expression; CELSR2, as a regulator of these genes, suggests a potential influence on energy metabolism through muscle oxidative capacity.</p><p><strong>Conclusion: </strong>Variants in the CELSR2/PSRC1/SORT1 locus exhibit tissue-specific effects on metabolic traits, with an independent role in muscle metabolism through glucocorticoid signaling.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"480-488"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635616","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":"Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings From the 4C Study.","authors":"Xiaojing Jia, Hong Lin, Yilan Ding, Xuejiang Gu, Shuangyuan Wang, Yu Xu, Min Xu, Xinjie Zhao, Lulu Chen, Tianshu Zeng, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Guijun Qin, Qin Wan, Gang Chen, Xulei Tang, Zhengnan Gao, Feixia Shen, Ruying Hu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu","doi":"10.1210/clinem/dgae483","DOIUrl":"10.1210/clinem/dgae483","url":null,"abstract":"<p><strong>Context: </strong>Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies.</p><p><strong>Objective: </strong>This work aimed to investigate associations and genetic susceptibility between serum MCFAs and diabetes risk.</p><p><strong>Methods: </strong>We investigated baseline serum MCFAs (n = 5) in a nested case-control study comprising incident diabetes cases (n = 1707) and matched normoglycemic control individuals (n = 1707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants.</p><p><strong>Results: </strong>In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% CI) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = .042, .034, and .037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Statistically significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = .003).</p><p><strong>Conclusion: </strong>These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"441-451"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731610","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}