Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Consistently Low Serum Levels of MG-H1 Are Associated With a Lower Risk of Diabetic Kidney Disease.","authors":"Tomoka Nakamura, Tetsuro Tsujimoto, Kazuki Yasuda, Hiroshi Kajio, Kohjiro Ueki","doi":"10.1210/clinem/dgaf098","DOIUrl":"10.1210/clinem/dgaf098","url":null,"abstract":"<p><strong>Context: </strong>Diabetic kidney disease (DKD) is associated with an increased risk of cardiovascular events, end-stage renal disease, and mortality. Advanced glycation end products (AGEs) are related to DKD. However, data on the associations between long-term changes in AGEs and DKD are lacking.</p><p><strong>Objective: </strong>We aimed to ascertain whether a long-term shift in serum AGE levels is associated with DKD development and progression in patients with poorly controlled diabetes.</p><p><strong>Methods: </strong>The serum levels of the AGE, methylglyoxal-derived hydroimidazolone-1 (MG-H1) were measured twice in 160 patients with diabetes. We categorized patients whose serum MG-H1 levels were <2.5 µg/mL at both measurements as the consistently low MG-H1 group. The primary endpoints were new or worsening DKD, which was defined as the occurrence of either a 30% decline in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, development of macroalbuminuria, need for renal replacement therapy, or death due to renal disease. Hazard ratios (HRs) for new or worsening DKD, with 95% confidence intervals (CIs), were calculated using Cox proportional hazard models to compare the outcomes between the consistently low MG-H1 group and the other group.</p><p><strong>Results: </strong>Compared to the other group, the consistently low MG-H1 group had a significantly lower risk of new or worsening DKD, after adjusting for possible confounders (HR: 0.48; 95% CI, 0.29-0.81; P = .01). Furthermore, the same relationship was observed in patients without eGFR <30 mL/min/1.73 m2, advanced DKD, or cardiovascular events.</p><p><strong>Conclusion: </strong>Consistently low serum MG-H1 levels are associated with a lower frequency of DKD.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3189-3200"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477196","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":"Common and Rare DUOX Variants in Patients With Congenital Hypothyroidism: Case-control Study and Family-based Analysis.","authors":"Yaning Jia, Xiaoyu Wang, Liqin Zhang, Yanan Duan, Hui Zou, Fengqi Wang, Xiangju Liu, Miaomiao Li, Shiguo Liu","doi":"10.1210/clinem/dgaf109","DOIUrl":"10.1210/clinem/dgaf109","url":null,"abstract":"<p><strong>Context: </strong>Dual oxidases (DUOXs) are essential for thyroid hormone synthesis. Rare DUOX variations have been detected in patients with congenital hypothyroidism (CH); however, their mode of inheritance and genotype-phenotype correlations remain unclear. Additionally, no study has determined whether common DUOX variants confer a risk of CH.</p><p><strong>Objective: </strong>To elucidate the molecular and clinical characteristics of CH caused by rare and common DUOX variants.</p><p><strong>Methods: </strong>Targeted next-generation sequencing was performed on 203 trios (parents and their child with CH) to screen for rare DUOX variants. For common variants, 8 tag single nucleotide polymorphisms (SNPs) were genotyped among 298 trios and 439 healthy controls. The association between these SNPs and CH risk was analyzed using a case-control study and a family-based transmission disequilibrium test.</p><p><strong>Results: </strong>The genetic contribution of rare DUOX variants to CH was 16.3% (DUOX2 14.3% and DUOXA2 2.0%). Familial cosegregation analysis suggested that DUOX variants were transmitted by an autosomal recessive pattern. These patients exhibited dyshormonogenesis and were more likely to develop into transient CH with the lower requirement of levothyroxine dose. Regarding common variants, 5 SNPs distributed across DUOXs were significantly associated with CH in both the case-control and family-based study. DUOX1 rs16939752 C > T and DUOXA1 rs3784576 C > A protected against CH, whereas DUOX2 rs269868 A > G, rs2001616 A > G and DUOXA2 rs2252371 T > C were associated with increased susceptibility to CH.</p><p><strong>Conclusion: </strong>Our research confirmed that DUOX variants are inherited in an autosomal recessive manner. We present a comprehensive spectrum of rare and common DUOX variants that provides more accurate insights into the pathogenesis of CH associated with DUOX.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3179-3188"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484593","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":"Antibodies Are Predictive for Diagnosis of Celiac Disease in Pediatric Type 1 Diabetes.","authors":"Nadja Zoe Müller, Iulia-Maia Muresan, Arnaud Künzi, Zamir-Zoran Borojevic, Barblin Remund, Marie-Anne Burckhardt, Claudia Boettcher, Christiane Sokollik","doi":"10.1210/clinem/dgaf146","DOIUrl":"10.1210/clinem/dgaf146","url":null,"abstract":"<p><strong>Background: </strong>Children and adolescents with type 1 diabetes (T1D) have a higher risk of developing celiac disease (CD) than the general population. However, the main screening antibody, IgA anti-transglutaminase 2 (TGA-IgA), can fluctuate in T1D and there is no threshold for performing diagnostic biopsies.</p><p><strong>Objectives: </strong>The study aims to define an optimal TGA-IgA cutoff for performing diagnostic biopsies for CD confirmation and to assess whether tracking TGA-IgA evolution or adding other antibodies can improve biopsy indications.</p><p><strong>Methods: </strong>Retrospective longitudinal analysis of pediatric T1D individuals diagnosed at 2 centers in Switzerland between 2000 and 2021, from T1D diagnosis to CD diagnosis or the age of 18 years.</p><p><strong>Results: </strong>We included 588 individuals with T1D, comprising 2944 TGA-IgA values. Thirty-four (5.8%) developed CD during follow-up, of whom 50% had CD-associated symptoms at CD diagnosis. Balancing sensitivity and specificity TGA-IgA around 6.1 × upper limit of normal was the best cutoff for performing diagnostic biopsies. The inclusion of IgG antibodies against deamidated gliadin peptides achieved a higher area under the curve of 0.79 (95% CI, 0.6-1) with 80% accuracy compared to each antibody alone. CD diagnosis within 2 years of T1D, representing two thirds of CD, was marked by elevated TGA-IgA at T1D diagnosis. Later CD diagnosis was associated with a more gradual increase of TGA-IgA.</p><p><strong>Conclusion: </strong>Our results suggest an indication for biopsy for CD confirmation at a TGA-IgA cutoff around 6.1 × upper limit of normal. Including IgG antibodies against deamidated gliadin peptides can potentially increase precision. TGA-IgA determination at T1D diagnosis may help to identify individuals at risk of CD early on.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3685-e3693"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582394","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":"Clinical Phenotype of Graves Disease in Autoimmune Polyglandular Syndrome or as Isolated Disease: The GRAPHE Study.","authors":"Elisa Gatta, Ilenia Pirola, Aurora Gotti, Micaela Fredi, Pietro Bellini, Francesco Dondi, Riccardo Morandi, Claudio Casella, Francesco Bertagna, Franco Franceschini, Mario Rotondi, Carlo Cappelli","doi":"10.1210/clinem/dgaf144","DOIUrl":"10.1210/clinem/dgaf144","url":null,"abstract":"<p><strong>Context: </strong>Graves disease (GD) can occur as an isolated condition or as part of an autoimmune polyglandular syndrome; there are no data regarding the differences in phenotype between these 2 forms.</p><p><strong>Objective: </strong>To assess differences in clinical presentation, complications, and outcomes in patients with isolated GD compared to those in whom GD is part of an autoimmune polyglandular syndrome.</p><p><strong>Methods: </strong>The GRAPHE study is a retrospective observational study. The medical records of all patients with GD diagnosed and regularly followed at outpatient clinics for Endocrinology, Nuclear Medicine and Clinical Surgery, from January 1, 2010, to June 30, 2024, were retrieved. All the patients were followed by the same endocrinologists and treated in accordance with existing guidelines.</p><p><strong>Results: </strong>The enrolled patients (n = 567; 77% women) were divided into 3 different groups based on GD phenotypes: subjects affected by isolated GD (isolated GD); patients who developed autoimmune polyglandular syndrome (GD1-APS); and patients with autoimmune polyglandular syndrome who developed GD during follow-up (GD2-APS). The 3 groups were superimposable for gender (P = .086), fT4 (P = .899), fT3 (P = .434), TRAb titers (P = .882), and thyroid volume (P = .840) at disease onset. Isolated GD patients exhibited Graves orbitopathy more frequently (P < .001), a higher rate of definitive therapy (P < .001) and shorter time between disease onset and definitive therapy (P < .001) compared to the GD1-APS and GD2-APS patients.</p><p><strong>Conclusion: </strong>The results of the present study show that, despite similar clinical and biochemical phenotype at presentation, a more severe clinical course characterizes isolated GD patients compared to those whose disease is a feature of autoimmune polyglandular syndrome.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3768-e3773"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558688","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":"Circulating Proteomic Profiles Are Associated With Incident Type 2 Diabetes in Asian Populations.","authors":"Yujian Liang, Charlie G Y Lim, Scott C Ritchie, Nicolas Bertin, Jin-Fang Chai, Jiali Yao, Yun Li, E Shyong Tai, Rob M van Dam, Xueling Sim","doi":"10.1210/clinem/dgaf045","DOIUrl":"10.1210/clinem/dgaf045","url":null,"abstract":"<p><strong>Context: </strong>Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. Previous T2D proteomic association studies primarily focused on European populations.</p><p><strong>Objective: </strong>The aim of this study was to investigate the relationship between plasma proteins and the incidence of T2D in Asian individuals.</p><p><strong>Methods: </strong>We examined the association of 4775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1659 Asian individuals (539 cases and 1120 controls) using logistic regression. We used 2-sample mendelian randomization and colocalization analysis to evaluate the causal relationship between proteins and T2D.</p><p><strong>Results: </strong>Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity, and 17 proteins that remained statistically significantly associated after adjusting for other T2D risk factors such as fasting glucose, waist circumference, and triglycerides. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and 6-year follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample mendelian randomization analysis suggested 3 plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC.</p><p><strong>Conclusion: </strong>Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3391-e3400"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025715","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":"Potential Mechanism Associated with Post-Heart Transplantation Diabetes Mellitus in Chinese Patients.","authors":"Xiao Huang, Qiling Xu, Linhua Chen, Li Liu, Ying Zhou, Hong Zhou, Yu Zhang","doi":"10.1210/clinem/dgaf071","DOIUrl":"10.1210/clinem/dgaf071","url":null,"abstract":"<p><strong>Context: </strong>Posttransplantation diabetes mellitus (PTDM) is a common metabolic complication following heart transplantation (HT), which not only leads to elevated microvascular morbidity, but also seriously affects graft function and recipient survival. However, the specific metabolites and underlying mechanisms are not yet fully understood.</p><p><strong>Objective: </strong>This study aimed to preliminarily screen out differentially expressed metabolites that are associated with PTDM in HT recipients and elucidate its potential pathophysiological mechanisms by using a global metabolomics approach, and provide a basis for the management of PTDM.</p><p><strong>Methods: </strong>A total of 106 adult HT recipients (56 PTDM and 50 non-PTDM) who were followed for more than 1 year were enrolled in the study. Untargeted metabolomics was performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Demographics, clinical data, and drug information were collected at the time of sample collection.</p><p><strong>Results: </strong>PTDM patients were older (P = .003), with higher body mass index scores (P = .010), higher triglyceride levels (P = .007), and a higher prevalence of hypertension (P = .001) than non-PTDM patients. A total of 1174 metabolites were detected, of which 99 metabolites showed significantly differentially abundant (VIP > 1; P < .05; FC > 1.5 or <0.67). KEGG functional enrichment analysis showed these differently expressed metabolites could be further enriched in ABC transporter, carbon metabolism, retrograde endocannabinoid signaling, and phospholipase D signaling pathway. Compared with the non-PTDM group, glutamate, diacylglycerol, and D-sorbitol were significantly changed in PTDM through metabolomics.</p><p><strong>Conclusion: </strong>These findings may provide a novel understanding of the pathological mechanism of PTDM and could be used to predict the development and progression of PTDM.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2800-2809"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076194","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":"Glucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.","authors":"RuoTong Zhou, Ruizhi Jiajue, Xiaolin Ni, Qianqian Pang, Yue Chi, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Lijia Cui, Xiang Li, Yong Liu, Huanwen Wu, Jin Jin, Wei Lv, Yu Xia, Li Huo, Lian Zhou, Wei Yu, XunWu Meng, Weibo Xia","doi":"10.1210/clinem/dgae886","DOIUrl":"10.1210/clinem/dgae886","url":null,"abstract":"<p><strong>Context: </strong>Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated.</p><p><strong>Objectives: </strong>This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis.</p><p><strong>Methods: </strong>20 TIO patients, 20 individuals with normal glucose tolerance, and 20 patients with type 2 diabetes mellitus (DM) were enrolled and underwent an oral glucose tolerance test (OGTT). Serum phosphate and FGF23 concentration were monitored during OGTT.</p><p><strong>Results: </strong>In patients with TIO, 60% (12/20) exhibited impaired glucose tolerance (IGT) and 5% (1/20) had type 2 DM. Those with IGT or type 2 DM experienced more ambulatory difficulties (69.2% vs 42.9%), lower phosphate concentrations (0.43 ± 0.10 vs 0.53 ± 0.10, P = .042), and lower calcium concentrations (2.20 ± 0.08 vs 2.30 ± 0.40, P = .001) compared to TIO patients without these conditions. According to correlation analysis, serum phosphate levels were negatively correlated with plasma glucose levels at 60 minutes (P < .001), fasting plasma insulin levels (P < .05), and homeostasis model assessment for insulin resistance (P < .05). Those with high FGF23 levels had a higher glucose level at 60 minutes (10.5 [9.3, 12.3] vs 7.3 [6.4, 10.1], P = .048) than that of low group. After glucose loading, both FGF23 and phosphate levels exhibited a decreasing trend.</p><p><strong>Conclusion: </strong>The development of diabetes in TIO patients may be predisposed by ambulatory issues, low phosphate, and elevated FGF23 levels. Dysglycemia might further aggravate hypophosphatemia.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2869-2878"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053830","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":"Using a Composite Summary of Daily Sex Hormones to Gauge Time Until Menopause: A Focus on Pregnanediol Glucuronide (PDG).","authors":"J F Winkles, Alicia Colvin, Samar R El Khoudary, Nanette Santoro, Mary Sammel, Sybil Crawford","doi":"10.1210/clinem/dgae895","DOIUrl":"10.1210/clinem/dgae895","url":null,"abstract":"<p><strong>Context: </strong>The timing of a woman's final menstrual period (FMP) in relation to her age is considered a valuable indicator of overall health, being associated with cardiovascular, bone health, reproductive, and general mortality outcomes.</p><p><strong>Objective: </strong>This work aimed to evaluate the relationship between hormones and the \"time to FMP\" when daily hormone trajectories are characterized by their 1) entropy, and 2) deviation from premenopausal/stable cycle patterns (representing a textbook \"gold standard\"; GS).</p><p><strong>Methods: </strong>As part of the Study of Women's Health Across the Nation, urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen conjugates (E1C), and pregnanediol glucuronide (PDG) were measured daily from a multiracial sample of 549 mid-life women for the duration of one menstrual cycle. Hormone trajectories were mapped onto a plane with axes representing Fuzzy entropy (FuzzEn) and the normalized dynamic time warping distance (DTW) from the GS.</p><p><strong>Results: </strong>Viewing FSH, E1C, PDG, and LH through this lens reveals that, contrary to existing wisdom, PDG stands out as a powerful predictor/descriptor of \"time to FMP.\" Using cluster analyses to discretize PDG on the DTW/FuzzEn plane yields statistically different survival curves, and Cox proportional hazards analyses confirm that this separation persists in the presence of known covariates of FSH, antimüllerian hormone, age, body mass index, financial hardship, smoking status, and cycle length.</p><p><strong>Conclusion: </strong>Since PDG is generally not considered a predictor/descriptor of ovarian aging, this work validates the DTW/FuzzEn analytical framework and introduces another metric/hormone to be used in FMP-related preventive care.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2832-2844"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025720","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":"Changes in 90-Day Time in Range Among Youth With Type 1 Diabetes Initiating Different Automated Insulin Delivery Systems.","authors":"Sonia Gera, Andrew Rearson, Greyson Baker, Julia L Douvas, Nicole Alicea-Trelles, Robert J Gallop, Seema Meighan, Brynn E Marks","doi":"10.1210/clinem/dgaf006","DOIUrl":"10.1210/clinem/dgaf006","url":null,"abstract":"<p><strong>Context: </strong>Glycemic outcomes in youth with type 1 diabetes (T1D) in the United States using the 2 most common automated insulin delivery (AID) systems, Insulet Omnipod 5 (OP5) and Tandem Control IQ (CIQ), have not been compared.</p><p><strong>Objective: </strong>We performed the first head-to-head analysis of changes in glycemic metrics among youth initiating AID.</p><p><strong>Methods: </strong>This single-center, retrospective study included youth < 21 years with T1D, who started OP5 or CIQ between January 2020 and December 2023, and had ≥ 70% continuous glucose monitoring (CGM) active time. We obtained 14-day baseline and 90-day CGM and AID data. A multiple linear regression model assessed for changes in 90-day time in range (TIR) according to AID system, adjusting for covariates. Subanalyses were conducted according to baseline TIR categories.</p><p><strong>Results: </strong>Among the 428 included youth, there were 214 (50%) in each AID group. OP5 users had a shorter T1D duration (1.6 vs 5.5 years, P < .001) and were more likely to have transitioned from multiple daily injections (76.1% vs 20.1%, P < .001). Baseline TIR was similar between groups (OP5 51.6% vs CIQ 53.1%, P = .70). 90-day TIR increased in both groups (P < .001), rising by 11.8 percentage points (95% CI [10.4, 13.3]) in OP5 users and 9.8 percentage points (95% CI [8.3, 11.2]) in CIQ users, without any significant between-group differences (P = .08). There were no between-group differences in 90-day TIR according to categorical baseline TIR.</p><p><strong>Conclusion: </strong>There are no clinically significant differences in 90-day TIR among youth with T1D initiating the 2 most commonly used AID systems. Patient preference and shared decision making should continue to guide the selection of AID systems.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3472-e3481"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015390","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":"Searching for Monogenic Autoimmune Etiology in Patients With Type 1 Diabetes Onset Before 30 Months of Age.","authors":"Laura Saso-Jiménez, Inés Urrutia, Begona Calvo, José Ramón Bilbao, Ana Lucía Gómez-Gila, Isabel Leiva-Gea, Andrea Jiménez-Sanchis, Itxaso Rica, Luis Castano, Rosa Martínez","doi":"10.1210/clinem/dgaf049","DOIUrl":"10.1210/clinem/dgaf049","url":null,"abstract":"<p><strong>Introduction: </strong>The most frequent form of diabetes in pediatric patients is polygenic autoimmune diabetes (type 1 diabetes [T1D]), but single-gene variants responsible for autoimmune diabetes have also been described. Both disorders share clinical features, which can lead to monogenic forms being misdiagnosed as T1D. However, correct diagnosis is crucial for therapeutic choice, prognosis, and genetic counseling. The aim of this study was to search for monogenic autoimmune diabetes in Spanish pediatric patients with early-onset T1D.</p><p><strong>Methods: </strong>Among 500 Spanish pediatric patients with T1D, those with disease onset between 9 and 30 months of age were selected for screening for monogenic autoimmune diabetes (n = 44). Genetic testing was performed by next-generation sequencing with a customized panel that included the major causative genes for monogenic autoimmune syndromes, including early-onset diabetes: AIRE, CTLA4, FOXP3, IL2RA, ITCH, LRBA, STAT1, STAT3, STAT5B. RT-PCR and cDNA sequencing of the RNA isolated from whole blood were used to analyze splicing variants.</p><p><strong>Results: </strong>Genetic screening identified, in 2 patients with diabetes onset before 1 year of age, 2 likely pathogenic novel variants affecting canonical splicing sites: c.286-12_290del in STAT5B and c.-22-2delA in FOXP3. RNA analyses demonstrated that both variants modify mRNA splicing. The variant in STAT5B induced exon 4 skipping and the variant in FOXP3 caused a deletion of 16 nucleotides before the transcription start site.</p><p><strong>Conclusion: </strong>T1D onset in the first year of life may indicate monogenic autoimmune diabetes and molecular testing may be recommended.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2853-2860"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054039","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}