Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"A Low-Intensity Nutrition Intervention Targeting Triglycerides in Gestational Diabetes: A Feasibility RCT.","authors":"Kai Liu, Georgia S Clarke, Jessica A Grieger","doi":"10.1210/clinem/dgaf291","DOIUrl":"10.1210/clinem/dgaf291","url":null,"abstract":"<p><strong>Context: </strong>The conventional approach to diet therapy for gestational diabetes mellitus (GDM) is carbohydrate modification to mitigate glucose-mediated fetal macrosomia. Maternal triglyceride concentrations more strongly relate to infant adiposity than maternal glucose.</p><p><strong>Objective: </strong>This work aimed to assess the feasibility of a low-intensity dietary intervention designed to attenuate the rise in triglycerides compared to standard GDM management.</p><p><strong>Methods: </strong>Women with GDM were randomly assigned at approximately 30 weeks' gestation to a standard care group (ie, usual GDM management) or to an intervention group, at an allocation ratio of 1:1. The intervention group received standard care plus individual counseling on reducing intake of ultraprocessed foods, increasing fruits, vegetables, fish and nuts, and changes to healthier fats. The primary outcome is study feasibility; secondary and exploratory outcomes include maternal dietary intakes, plasma triglyceride and glucose levels, and birth weight.</p><p><strong>Results: </strong>Over 10 months of active recruitment, 444 women were invited to participate. Of these, 59 were eligible (13.2%), 38 (8.6%) consented and were randomly assigned (n = 19 intervention, n = 19 standard care), and 34 women completed the study. The recruitment rate was 1 per week, the retention rate was 89.5%, and the feasibility of eligibility criteria was 70.4%. Nearly all women in the intervention group who responded to the questionnaire (n = 15/16) reduced their ultraprocessed food intake, and 11 women increased their intake of nuts. There was no end of study differences in nonfasting plasma triglycerides (mean [95% CI] in intervention, 2.84 [2.22-3.46] mmol/L vs standard care, 3.40 [2.78-4.02] mmol/L). Mean birthweight was higher in the standard care group vs intervention group (mean difference [95% CI], 479.5 [110.7-848.3] g).</p><p><strong>Conclusion: </strong>There was a modest recruitment rate and a high retention rate, indicating a diet aimed at attenuating triglycerides is feasible and highly acceptable in women with GDM. The positive improvements observed in maternal diet and desirable birth weight warrant further investigation in a larger, definitive, randomized controlled trial.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"218-228"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081687","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":"Biomarkers of Insulin Resistance and Their Performance as Predictors of Treatment Response in Overweight Adults.","authors":"Robert J Brogan, Olav Rooyackers, Bethan E Phillips, Brigitte Twelkmeyer, Leanna M Ross, Philip J Atherton, William E Kraus, James A Timmons, Iain J Gallagher","doi":"10.1210/clinem/dgaf285","DOIUrl":"10.1210/clinem/dgaf285","url":null,"abstract":"<p><strong>Context: </strong>Insulin resistance (IR) contributes to the pathogenesis of type 2 diabetes mellitus and is a risk factor for cardiovascular and neurodegenerative diseases. Amino acid and lipid metabolomic biomarkers associate with future type 2 diabetes mellitus risk in several epidemiological cohorts. Whether these biomarkers can accurately monitor changes in IR status following treatment is unclear.</p><p><strong>Objective: </strong>Herein we evaluated the performance of clinical and metabolomic biomarker models to forecast altered IR, following lifestyle-based interventions.</p><p><strong>Design: </strong>We contrasted the performance of two distinct insulin assay types (high-sensitivity ELISA and immunoassay) and built IR diagnostic models using cross-sectional clinical and metabolomic data. These models were used to stratify IR status in preintervention fasting samples, from 3 independent cohorts (META-PREDICT (n = 179), STRRIDE-AT/RT (n = 116), and STRRIDE-PD (n = 149)). Linear and Bayesian projective prediction strategies were used to evaluate models for fasting insulin and homeostatic model assessment 2 for insulin resistance and change in fasting insulin with treatment.</p><p><strong>Results: </strong>Both insulin assays accurately quantified international standard insulin (R2 > 0.99), yet agreement between fasting insulins was less congruent (R2 = 0.65). A mean treatment effect on fasting insulin was only detectable using the ELISA. Clinical-metabolomic models were statistically related to fasting insulin (R2 0.33-0.39) but with modest capacity to classify IR at a clinically relevant homeostatic model assessment 2 for insulin resistance threshold. Furthermore, no model predicted treatment responses in any cohort.</p><p><strong>Conclusion: </strong>We demonstrate that the choice of insulin assay is critical when quantifying the influence of treatment on fasting insulin, whereas none of the clinical-metabolomic biomarkers, identified in cross-sectional studies, are suitable for monitoring longitudinally changes in IR status.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"244-255"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052215","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":"Urine Choline Oxidation Metabolites Predict Chronic Kidney Disease Progression in Patients With Type 2 Diabetes.","authors":"Jian-Jun Liu, Sylvia Liu, Resham L Gurung, Janus Lee, Huili Zheng, Keven Ang, Clara Chan, Lye Siang Lee, Sharon Han, Jean-Paul Kovalik, Jianhong Ching, Pierre-Jean Saulnier, Samy Hadjadj, Thomas M Coffman, Su Chi Lim","doi":"10.1210/clinem/dgaf281","DOIUrl":"10.1210/clinem/dgaf281","url":null,"abstract":"<p><strong>Context: </strong>Choline is metabolized in kidney tubules but the relationship between choline metabolism and kidney disease has not been systematically characterized.</p><p><strong>Objective: </strong>To study whether urine metabolites in the choline oxidation pathway may predict the risk of chronic kidney disease (CKD) progression in individuals with type 2 diabetes.</p><p><strong>Methods: </strong>Outpatients (n = 1894) with type 2 diabetes were recruited from a secondary hospital and a primary care facility. Urine choline, betaine, dimethylglycine, and sarcosine were measured by liquid chromatography-mass spectrometry. CKD progression was defined as a composite of incident end-stage kidney disease (sustained eGFR <15 mL/min/1.73m2, maintenance dialysis, renal death) and doubling of serum creatinine.</p><p><strong>Results: </strong>CKD progression occurred in 263 participants during a median follow-up of 9.2 years. High levels of urine choline and dimethylglycine were associated with an increased risk of CKD progression after adjustment for clinical risk factors (adjusted HR [95% CI], 1.32 [1.16-1.51] and 1.30 [1.14-1.47], respectively, per 1 SD). Urine choline and dimethylglycine were positively correlated with tubulopathy biomarkers, especially dickkopf-related protein 3 (dkk3, Spearman rho 0.55 and 0.53). The association between dkk3 and CKD progression was diminished but the association between choline, dimethylglycine, and CKD progression remained significant after mutual adjustments. Choline and dimethylglycine were also independently associated with risk of all-cause death (adjusted HR 1.20 [1.06-1.37] and 1.17 [1.04-1.33], respectively).</p><p><strong>Conclusion: </strong>Urine choline and dimethylglycine independently predict the risk of CKD progression in individuals with type 2 diabetes. Dysregulation of intrarenal choline metabolism may be involved in tubulopathy leading to progressive loss of kidney function.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e225-e233"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055675","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":"Novel and Ultrarare Heterozygous Missense LMNA Variants Causing Familial Partial Lipodystrophy.","authors":"Anum, Xilong Li, Abhimanyu Garg","doi":"10.1210/clinem/dgaf279","DOIUrl":"10.1210/clinem/dgaf279","url":null,"abstract":"<p><strong>Context: </strong>Familial partial lipodystrophy, type 2 (FPLD2) or the Dunnigan variety, is a rare, autosomal dominant disorder characterized by selective loss of subcutaneous fat from the extremities and is caused by over 50 heterozygous missense LMNA variants. However, some patients with FPLD2 do not harbor the known pathogenic LMNA variants and there are only limited genotype-phenotype segregation data for a few other variants.</p><p><strong>Objective: </strong>To report the genotype-phenotype relationships in 4 families with ultrarare and novel LMNA variants causing FPLD2.</p><p><strong>Methods: </strong>Clinical, anthropometric, and laboratory data of affected and unaffected subjects from 4 families with female probands presenting with FPLD2 phenotype were collected retrospectively. The main parameters were clinical phenotype, skinfold thickness, regional body fat by dual-energy X-ray absorptiometry (DXA), metabolic variables, and prevalence of diabetes mellitus and hypertriglyceridemia.</p><p><strong>Results: </strong>We found 2 ultrarare (p.N466D, and p.K515E) and 2 novel (p.R582S, and p.L241P) LMNA heterozygous variants in 4 unrelated FPLD2 families. All adult affected females had thigh skinfold thickness below the 10th percentile of normal and lower extremity fat below the 1st percentile of normal suggesting \"typical\" FPLD2. None of our patients had any cardiomyopathy, muscular dystrophy, neuropathy, or any progeroid features.</p><p><strong>Conclusion: </strong>Our data provide further supporting evidence for the pathogenicity of 2 previously reported ultrarare heterozygous LMNA variants, p.N466D and p.K515E. We also report 2 novel variants, p.R582S and p.L241P, in patients with FPLD2. Thus, our study broadens the spectrum of pathogenic/likely pathogenic LMNA variants in FPLD2.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e214-e224"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081803","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":"Women With Higher GCT Levels but NGT Have a Similarly High Risk for Glucose Intolerance Postpartum as Women With GDM.","authors":"Lore Raets, Kim Van Hoorenbeeck, Toon Maes, DaHae Lee, Christophe De Block, Eveline Dirinck, Inge Van Pottelbergh, Katrien Wierckx, Annouschka Laenen, Annick Bogaerts, Chantal Mathieu, Katrien Benhalima","doi":"10.1210/clinem/dgaf275","DOIUrl":"10.1210/clinem/dgaf275","url":null,"abstract":"<p><strong>Context: </strong>More data are needed on the long-term postpartum metabolic risk of women with hyperglycemia in pregnancy less than gestational diabetes mellitus (GDM) based on the 2013 World Health Organization criteria.</p><p><strong>Objective: </strong>This work aimed to determine the association of different degrees of gestational glucose intolerance (GI) on the metabolic profile and risk for GI in women and offspring 3 to 7 years postpartum.</p><p><strong>Methods: </strong>This multicentric prospective follow-up study of the Belgian Diabetes in Pregnancy study (BEDIP-N, which was a prospective observational study) included 334 women and 296 children. Groups were stratified according to antenatal glucose challenge test (GCT) and diagnosis of GDM based on the 2013 World Health Organization criteria: normal glucose tolerant women with normal GCT (normal GCT-NGT group), NGT with abnormal GCT (abnormal GCT-NGT group), and a GDM group. Logistic regression was performed to adjust for following confounders: time since participation in BEDIP-N, ethnicity, prepregnancy body mass index (BMI), age, and current BMI.</p><p><strong>Results: </strong>The GCT cutoff with the highest Youden index to predict GI in mothers 5.7 years postpartum was greater than or equal to 8.3 mmol/L (≥150 mg/dL). NGT women with GCT greater than or equal to 8.3 mmol/L (abnormal GCT-NGT group, n = 39) had a similarly increased risk for GI as women with GDM (n = 82) with an adjusted odds ratio of 2.87 (1.47-5.60; P = .0020) compared to the normal GCT-NGT group (n = 213). β-Cell function decreased over the different gestational glucose tolerance groups, with similar β-cell dysfunction in the GDM and abnormal GCT-NGT groups. Offspring of women with hyperglycemia less than GDM did not have an increased risk for an adverse metabolic profile postpartum.</p><p><strong>Conclusion: </strong>NGT women with GCT greater than or equal to 8.3 mmol/L (≥150 mg/dL) in pregnancy have a similarly high risk for GI 5.7 years postpartum as women with GDM. These women also need postpartum follow-up to prevent GI.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e281-e291"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042702","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":"Relationship Between Insulin Sensitivity and Hyperinsulinemia in Early Insulin Resistance is Sex-dependent.","authors":"Sarah J Blackwood, Dominik Tischer, Marjan Pontén, Marcus Moberg, Abram Katz","doi":"10.1210/clinem/dgaf282","DOIUrl":"10.1210/clinem/dgaf282","url":null,"abstract":"<p><strong>Context: </strong>Insulin resistance (IR) is a major risk factor for the development of several diseases that have reached epidemic proportions worldwide, including hypertension, obesity, and type 2 diabetes. In many disease states, IR is associated with fasting hyperinsulinemia/excessive glucose-stimulated insulin secretion. However, it is not known whether hyperinsulinemia precedes/leads to the natural development of IR or vice versa.</p><p><strong>Objective: </strong>Here, we assess the relationship between hyperinsulinemia and insulin sensitivity in a cohort of healthy young lean men and women, where IR is observed in those who exhibit a low expression of type I skeletal muscle fibers and a high resting heart rate.</p><p><strong>Methods: </strong>Biopsies were obtained from the vastus lateralis muscle, followed by an IV glucose tolerance test. Insulin secretion and whole-body insulin sensitivity were calculated.</p><p><strong>Results: </strong>In this young population of normoglycemic, glucose-tolerant individuals, insulin sensitivity was significantly and negatively associated with fasting levels of plasma insulin, as well as insulin secretion in response to glucose infusion. Surprisingly, however, all the correlations became stronger when calculated in women, but became insignificant when calculated in men. In contrast, insulin sensitivity was significantly correlated with expression of type I skeletal muscle fibers and resting heart rate to similar extents in both sexes.</p><p><strong>Conclusion: </strong>In the natural development of IR in men, it appears that hyperinsulinemia is a compensatory adaptation to peripheral IR rather than its cause.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e234-e239"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058977","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":"Does Insulin Work as Good One or Bad One for the Cardiovascular Tissues?","authors":"Yoshihiko Nishio","doi":"10.1210/clinem/dgaf051","DOIUrl":"10.1210/clinem/dgaf051","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e302-e303"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574532","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":"Propionate Induces Energy Expenditure via Browning in Mesenteric Adipose Tissue.","authors":"Baichen Lu, Aylin C Hanyaloglu, Yue Ma, Adam E Frampton, Christopher Limb, Nabeel Merali, Madhava Pai, Rehan Ahmed, Mark Christian, Gary Frost","doi":"10.1210/clinem/dgaf280","DOIUrl":"10.1210/clinem/dgaf280","url":null,"abstract":"<p><strong>Context: </strong>Short-chain fatty acids, such as propionate, are produced from the fermentation of dietary fiber by gut microbiota and modulate adipose tissue (AT) metabolism to influence whole-body metabolic processes. Abdominal AT, critical in glucose and lipid homeostasis, is categorized into mesenteric, omental, and subcutaneous types based on its location. ATs display different metabolic phenotypes due to their distinct adipocyte lineages-white, brown, and beige. Recent evidence points to a significant effect of propionate on abdominal AT.</p><p><strong>Objective: </strong>Our study investigated the actions of propionate on the 3 types of human abdominal AT.</p><p><strong>Methods: </strong>AT from distinct depots (mesenteric, omental, and subcutaneous) were collected from 40 patients who underwent open abdominal surgery for cholecystectomy or explorative laparotomy. Tissue explants and isolated adipocytes were treated with 1 mM propionate to assess AT browning and metabolic homeostasis.</p><p><strong>Results: </strong>Propionate upregulated brown fat markers UCP1 and PGC1α in adipose tissue and mature adipocytes, particularly of mesenteric origin. Propionate exposure led to increased mitochondrial respiration and adenosine triphosphate production, primarily in mesenteric adipocytes, along with improved glucose uptake and reduced lipolysis and inflammation. In addition, propionate increased thermogenesis, glycolysis, and lipogenesis.</p><p><strong>Conclusion: </strong>The pronounced response of mesenteric AT to propionate underscores its potential as a therapeutic target for managing abdominal obesity and metabolic disorders.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"256-267"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042303","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":"Genetic and Epigenetic Contributions to Central Precocious Puberty.","authors":"Ursula B Kaiser","doi":"10.1210/clinem/dgaf130","DOIUrl":"10.1210/clinem/dgaf130","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e306-e307"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558691","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":"Comments on Injectable Estradiol Use in Transgender and Gender-diverse Individuals in the United States.","authors":"Christina Milano, Joanna Harper","doi":"10.1210/clinem/dgaf134","DOIUrl":"10.1210/clinem/dgaf134","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e304-e305"},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558689","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}