Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1365700
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
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.
{"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}
Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1436678
C. Fotakis, Maria Gazouli, Silvia Turroni
{"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}
Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1345573
Taishun Li, Mingyang Xu, Yuan Wang, Ya Wang, H. Tang, Honglei Duan, Guangfeng Zhao, M. Zheng, Yali Hu
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.
子痫前期是一种发病机制不明的疾病，也是孕产妇和围产期发病率的主要原因之一。目前，早期识别子痫前期的高危人群并及时使用阿司匹林进行干预是预防子痫前期的有效方法。本研究旨在通过机器学习算法，基于孕 11-13+6 周时的母体特征、生物物理和生物化学标志物，建立一个稳健有效、性能良好的子痫前期预测模型，为子痫前期的早期筛查和预测提供有效工具。研究收集了母体特征（如母体年龄、身高、孕前体重）、既往病史、平均动脉压、子宫动脉搏动指数、妊娠相关血浆蛋白 A 和胎盘生长因子作为子痫前期预测模型的协变量。预测模型的开发采用了五种分类算法，包括逻辑回归、额外树分类器、投票分类器、高斯过程分类器和堆叠分类器。最终，我们从 4644 名孕妇的数据中筛选出 49 例子痫前期和 161 例子痫前期。与其他预测算法相比，投票分类器算法的AUC和10%FPR时的检出率在预测早产子痫前期时表现更好（AUC=0.884，10%FPR时的DR=0.625）。然而，在所有子痫前期和子痫期预测中，其表现与其他模型算法相似。在预测所有子痫前期时，PLGF 的贡献率高于 PAPP-A（11.9% VS 8.7%），而在预测早产子痫前期时，情况正好相反（7.2% VS 16.5%）。在相同的预测因素下，使用机器学习算法预测子痫前期或先兆子痫的效果与胎儿医学基金会竞争风险模型的效果相似（PE和先兆子痫的AUC分别为0.797和0.856）。
{"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}
Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1396465
Haibin Wen, Xianhua Li, Jiangming Chen, Yi Li, Nailong Yang, Ning Tan
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.
氧化平衡评分（OBS）可量化受饮食和生活方式影响的抗氧化剂和促氧化剂之间的平衡，鉴于氧化应激在慢性肾脏病（CKD）中的重要作用，该评分至关重要。本研究旨在利用美国国家健康与营养调查（NHANES）1999-2018 年的数据，确定 OBS 与 CKD 之间的关联。OBS由20个因素组成，包括膳食营养素和生活方式行为。采用加权逻辑回归模型评估了OBS与CKD风险之间的关系，并对潜在的混杂因素进行了调整，用广义加法模型（GAM）检验了非线性关联。在分析的32120名参与者中，有4786人被确认患有慢性肾脏病。完全调整加权逻辑回归分析显示，OBS 每增加一个单位，CKD 患病率就会降低 2% [OR: 0.98 (0.98-0.99)，P < 0.001]。OBS 四分位数越高，患慢性肾脏病的风险越低 [Q4 vs. Q1: OR: 0.82 (0.68-0.98), P = 0.03; P for trend = 0.01]。GAM和平滑曲线拟合表明，OBS与CKD风险之间存在线性关系。我们从 NHANES 数据中得出的研究结果证实，在美国人群中，OBS 与 CKD 风险之间存在显著的反比关系，强调了优化饮食和生活方式因素在控制 CKD 风险中的作用。这些结果主张将 OBS 纳入 CKD 预防和治疗策略中。
{"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}
Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1360851
Wenke Zhang, Erhao Liu, Huafa Que
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.
{"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}
Pub Date : 2024-06-11DOI: 10.3389/fendo.2024.1385583
Zhenglin He, H. Yamana, Hideo Yasunaga, Hongjun Li, Xue Wang
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.
{"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}
Pub Date : 2024-06-10DOI: 10.3389/fendo.2024.1435877
H. Virtanen, Katharina M. Main, J. Toppari
{"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}
Pub Date : 2024-06-10DOI: 10.3389/fendo.2024.1366290
Hu Li, Wei Li, Dongyang Li, Lijuan Yuan, Yucheng Xu, Pengtao Su, Liqiang Wu, Zhiqiang Zhang
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.
{"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}
Pub Date : 2024-06-10DOI: 10.3389/fendo.2024.1414447
Sumitkumar Patel, M. Remedi
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.
{"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}
Pub Date : 2024-06-10DOI: 10.3389/fendo.2024.1366297
Xiaoyuan Tian, Zhenan Qu, Ying Cao, Bocheng Zhang
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.
这项荟萃分析旨在评估间充质干细胞（MSCs）治疗膝骨关节炎（OA）的有效性和安全性。研究人员检索了PubMed、Embase、Cochrane Central Register of Controlled Trials、Scopus和Web of Science等数据库，时间跨度从开始到2024年5月6日，以确定比较间充质干细胞和安慰剂或其他非手术疗法治疗OA的随机对照试验。两名研究人员独立检索文献并提取数据，使用Review Manager 5.3进行常规荟萃分析。结果包括疼痛缓解、功能改善和不良事件（AEs）风险。总体而言，在12个月的随访中，间充质干细胞在缓解疼痛和改善功能方面优于安慰剂。然而，治疗相关的AEs差异并不显著。本研究的局限性包括所纳入研究的高度异质性。此外，纳入研究的随访时间相对较短，因此需要更多的临床试验来预测间充质干细胞的长期疗效和安全性。https://doi.org/10.17605/OSF.IO/5BT6E，标识符为CRD42022354824。
{"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}
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