Frontiers in Endocrinology最新文献

{"title":"Case report: The success of empagliflozin therapy for glycogen storage disease type 1b","authors":"Ana Klinc, U. Groselj, M. Mlinaric, Matjaz Homan, Gašper Markelj, Ajda Mezek Novak, Andreja Širca Čampa, J. Sikonja, T. Battelino, M. Zerjav Tansek, Ana Drole Torkar","doi":"10.3389/fendo.2024.1365700","DOIUrl":"https://doi.org/10.3389/fendo.2024.1365700","url":null,"abstract":"Glycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date.A retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected.During the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"66 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141358430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Omics approaches to delineate the role of gut microbiota-derived metabolites in obesity and metabolic disorders","authors":"C. Fotakis, Maria Gazouli, Silvia Turroni","doi":"10.3389/fendo.2024.1436678","DOIUrl":"https://doi.org/10.3389/fendo.2024.1436678","url":null,"abstract":"","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"98 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141359364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction model of preeclampsia using machine learning based methods: a population based cohort study in China","authors":"Taishun Li, Mingyang Xu, Yuan Wang, Ya Wang, H. Tang, Honglei Duan, Guangfeng Zhao, M. Zheng, Yali Hu","doi":"10.3389/fendo.2024.1345573","DOIUrl":"https://doi.org/10.3389/fendo.2024.1345573","url":null,"abstract":"Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11–13 + 6 weeks’ gestation, providing an effective tool for early screening and prediction of preeclampsia.This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation.We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively).Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"56 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141358351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of oxidative balance score with chronic kidney disease: NHANES 1999-2018","authors":"Haibin Wen, Xianhua Li, Jiangming Chen, Yi Li, Nailong Yang, Ning Tan","doi":"10.3389/fendo.2024.1396465","DOIUrl":"https://doi.org/10.3389/fendo.2024.1396465","url":null,"abstract":"The Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative stress’s significant role in Chronic Kidney Disease (CKD). This study aims to determine the association between OBS and CKD using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. OBS was constructed from a detailed array of 20 factors, including dietary nutrients and lifestyle behaviors. The relationship between OBS and CKD risk was evaluated using weighted logistic regression models, adjusted for potential confounders, with a generalized additive model (GAM) examining non-linear associations. Subgroup analyses and interaction effects across diverse demographic and clinical groups, along with sensitivity analyses, were performed to validate the findings.Among 32,120 participants analyzed, 4,786 were identified with CKD. Fully adjusted weighted logistic regression analysis revealed that each unit increase in OBS was associated with a 2% reduction in CKD prevalence [OR: 0.98 (0.98–0.99), P < 0.001]. Higher OBS quartiles were significantly correlated with a decreased CKD risk [Q4 vs. Q1: OR: 0.82 (0.68–0.98), P = 0.03; P for trend = 0.01]. The GAM and smoothed curve fit indicated a linear relationship between OBS and the risk of CKD. Stratified and sensitivity analyses further substantiated the inverse relationship between OBS and CKD prevalence.Our findings from the NHANES data affirm a significant inverse association between OBS and CKD risk in the U.S. population, underscoring the role of optimizing dietary and lifestyle factors in managing CKD risk. These results advocate for incorporating OBS considerations into CKD prevention and treatment strategies.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"16 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141356097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of circulating vitamin levels with thyroid diseases: a Mendelian randomization study","authors":"Wenke Zhang, Erhao Liu, Huafa Que","doi":"10.3389/fendo.2024.1360851","DOIUrl":"https://doi.org/10.3389/fendo.2024.1360851","url":null,"abstract":"Previous observational studies have shown conflicting results of vitamins supplementation for thyroid diseases. The causal relationships between vitamins and thyroid diseases are unclear. Therefore, we conducted a two-sample bidirectional Mendelian randomization (MR) study to explore association of circulating vitamin levels with thyroid diseases.We performed a bidirectional MR analysis using genome-wide association study (GWAS) data. Genetic tool variables for circulating vitamin levels include vitamins A, B9, B12, C, D, and E, Genetic tool variables of thyroid diseases include autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid nodules (TNs), and Thyroid cancer (TC). Inverse-variance weighted multiplicative random effects (IVW-RE) was mainly used for MR Analysis, weighted median (WM) and MR Egger were used as supplementary methods to evaluate the relationships between circulating vitamin levels and thyroid diseases. Sensitivity and pluripotency were evaluated by Cochran’s Q test, MR-PRESSO, Radial MR, MR-Egger regression and leave-one-out analysis.Positive MR evidence suggested that circulating vitamin C level is a protective factor in autoimmune hypothyroidism (ORIVW-RE=0.69, 95%CI: 0.58-0.83, p = 1.05E-04). Reverse MR Evidence showed that genetic susceptibility to autoimmune hyperthyroidism is associated with reduced level of circulating vitamin A(ORIVW-RE = 0.97, 95% CI: 0.95–1.00, p = 4.38E-02), genetic susceptibility of TNs was associated with an increased level of circulating vitamin D (ORIVW-RE = 1.02, 95% CI: 1.00–1.03, p = 6.86E-03). No causal and reverse causal relationship was detected between other circulating vitamin levels and thyroid diseases.Our findings provide genetic evidence supporting a bi-directional causal relationship between circulating vitamin levels and thyroid diseases. These findings provide information for the clinical application of vitamins prevention and treatment of thyroid diseases.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"98 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141359264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of risk factors and clinical implications for diabetes in first-degree relatives in the northeastern region of China","authors":"Zhenglin He, H. Yamana, Hideo Yasunaga, Hongjun Li, Xue Wang","doi":"10.3389/fendo.2024.1385583","DOIUrl":"https://doi.org/10.3389/fendo.2024.1385583","url":null,"abstract":"The prevalence of diabetes has risen fast with a considerable weighted prevalence of undiagnosed diabetes or uncontrolled diabetes. Then it becomes more necessary to timely screen out and monitor high-risk populations who are likely to be ignored during the COVID-19 pandemic. To classify and find the common risks of undiagnosed diabetes and uncontrolled diabetes, it’s beneficial to put specific risk control measures into effect for comprehensive primary care. Especially, there is a need for accurate yet accessible prediction models.Based on a cross-sectional study and secondary analysis on the health examination held in Changchun City (2016), we aimed to evaluate the factors associated with hyperglycemia, analyze the management status of T2DM, and determine the best cutoff value of incidence of diabetes in the first-degree relatives to suggest the necessity of early diagnosis of diabetes after first screening.A total of 5658 volunteers were analyzed. Prevalence of T2DM and impaired fasting glucose were 8.4% (n=477) and 11.5% (n=648), respectively. There were 925 participants (16.3%) with a family history of T2DM in their first-degree relatives. Multivariable analysis demonstrated that family history was associated with hyperglycemia. Among the 477 patients with T2DM, 40.9% had not been previously diagnosed. The predictive equation was calculated with the following logistic regression parameters with 0.71 (95% CI: 0.67–0.76) of the area under the ROC curve, 64.0% of sensitivity and 29% of specificity (P < 0.001): P = frac{1}{1 + e^{-z}}, where z = -3.08 + [0.89 (Family history-group) + 0.69 (age-group)+ 0.25 (BMI-group)]. Positive family history was associated with the diagnosis of T2DM, but not glucose level in the diagnosed patients. The best cutoff value of incidence of diabetes in the first-degree relatives was 9.55% (P < 0.001).Family history of diabetes was independently associated with glucose dysfunction. Classification by the first-degree relatives with diabetes is prominent for targeting high-risk population. Meanwhile, positive family history of diabetes was associated with diabetes being diagnosed rather than the glycemic control in patients who had been diagnosed. It’s necessary to emphasize the linkage between early diagnosis and positive family history for high proportions of undiagnosed T2DM.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"23 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141356107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Update on epidemiology, endocrinology and treatment of cryptorchidism","authors":"H. Virtanen, Katharina M. Main, J. Toppari","doi":"10.3389/fendo.2024.1435877","DOIUrl":"https://doi.org/10.3389/fendo.2024.1435877","url":null,"abstract":"","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":" 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141365827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Based on systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for diabetes","authors":"Hu Li, Wei Li, Dongyang Li, Lijuan Yuan, Yucheng Xu, Pengtao Su, Liqiang Wu, Zhiqiang Zhang","doi":"10.3389/fendo.2024.1366290","DOIUrl":"https://doi.org/10.3389/fendo.2024.1366290","url":null,"abstract":"Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic “druggable” genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":"112 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141363000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of β-cell identity and dedifferentiation, not an irreversible process?","authors":"Sumitkumar Patel, M. Remedi","doi":"10.3389/fendo.2024.1414447","DOIUrl":"https://doi.org/10.3389/fendo.2024.1414447","url":null,"abstract":"Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β-cell apoptosis rates are relatively low in diabetes. Instead, β-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to β-cell failure. The underlying mechanisms driving β-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing β-cell dedifferentiation in T2D. This review explores the proposed drivers of β-cell dedifferentiation leading to β-cell failure, and discusses current interventions capable of reversing this process, thus restoring β-cell identity and function.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141365488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative efficacy and safety of mesenchymal stem cells for osteoarthritis: a systematic review and meta-analysis of randomized controlled trials","authors":"Xiaoyuan Tian, Zhenan Qu, Ying Cao, Bocheng Zhang","doi":"10.3389/fendo.2024.1366297","DOIUrl":"https://doi.org/10.3389/fendo.2024.1366297","url":null,"abstract":"The aim of this meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA). The PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science databases were searched from inception to May 6, 2024 to identify randomized controlled trials that compared MSCs and placebo or other nonsurgical approaches for treating OA. Two investigators independently searched the literature and extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes included pain relief, functional improvement, and risk of adverse events (AEs).A total of 18 articles were included. Overall, MSCs were superior to placebo in terms of relieving pain and improving function at the 12-month follow-up. However, the differences in treatment-related AEs were not significant.MSCs may relieving pain and improving function of OA. The limitations of this study include the high heterogeneity of the included studies. Additionally, the follow-up time in the included studies was relatively short, so more clinical trials are needed to predict the long-term efficacy and safety of MSCs.https://doi.org/10.17605/OSF.IO/5BT6E, identifier CRD42022354824.","PeriodicalId":505784,"journal":{"name":"Frontiers in Endocrinology","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141365958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}