Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

{"title":"Nomogram for Predicting Early AVF Failure in Elderly Diabetic Patients: Methodological and Clinical Considerations [Letter].","authors":"Shi-Cheng Liu, Kun Tian, Yu-Ting Zhang","doi":"10.2147/DMSO.S521525","DOIUrl":"https://doi.org/10.2147/DMSO.S521525","url":null,"abstract":"","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"677-678"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary-Thyroid Hormones and Related Indices in Euthyroid Type 2 Diabetes: Association With Thyroid Nodules.","authors":"Baolan Ji, Shuwei Shi, Hongyan Zhao, Xuan Ma, Jie Sheng, Bo Ban, Guanqi Gao","doi":"10.2147/DMSO.S503444","DOIUrl":"10.2147/DMSO.S503444","url":null,"abstract":"<p><strong>Aim: </strong>Diabetes is an independent risk factor for thyroid nodules (TNs), however, the influencing factors of TNs have not been fully clarified under the condition of diabetes. Previous studies have shown a connection between pituitary-thyroid hormone (TH) functions and TNs in different populations. However, the potential link in euthyroid patients with diabetes is unclear. We aimed to explore the correlates of TNs in euthyroid type 2 diabetes (T2D) patients.</p><p><strong>Methods: </strong>This cross-sectional study included 1965 euthyroid adults with T2D. Clinical and biochemical data, including TH and relevant covariates were collected. TNs were evaluated using ultrasound. Univariate and multivariate logistic regression analyses were performed to identify factors associated with TNs, with analyses stratified by sex.</p><p><strong>Results: </strong>The overall prevalence of TNs was 51.9%. The prevalence of TNs was higher in females. Stratified by sex, the results from univariate and further logistic regression analyses showed that free triiodothyronine (FT3) (OR: 1.381; 95% CI: 1.066-1.790) and thyroid-stimulating hormone index (TSHI) (OR: 0.740; 95% CI: 0.584-0.937) were independently correlated with TNs only in females, while no TH-related indicators entered the regression model in males.</p><p><strong>Conclusion: </strong>The relationship between TH and related indices with TNs exhibited sex differences. Specifically, FT3 and TSHI were independently associated with TNs in females. These findings underscore the importance of evaluating TH and related indices for early monitoring and management of TNs, particularly in euthyroid female T2D patients.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"627-636"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finerenone Ameliorates High Glucose-Induced Podocytes Epithelial-Mesenchymal Transition Through the Regulation of Krüppel-Like Factor 5 in Diabetic Nephropathy.","authors":"Jianqiang Shu, Dandan Chen, Wenzhen Chen, Xinyu Zhang, Simeng Wang, Nannan Chong, Zhikang Sun, Qinglian Wang, Jingshu Sun, Ying Xu","doi":"10.2147/DMSO.S503133","DOIUrl":"10.2147/DMSO.S503133","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy (DN) could impair the function of the glomerular filtration barrier by damaging the podocytes. Extant research has demonstrated that aldosterone plays a crucial role in this progression. Finerenone is a novel, high-selective mineralocorticoid receptor antagonist that has been demonstrated to be efficacious in renal protection in DN patients, albeit with an unclear underlying mechanism.</p><p><strong>Methods: </strong>Podocytes were stimulated with RPMI 1640 medium containing different concentrations of glucose and treated with finerenone to evaluate the protective effect of finerenone on podocytes in high glucose environment. Intraperitoneal injection of STZ was used to induce diabetic nephropathy rats and intragastric administration with finerenone or vehicles, and the changes of renal function, renal pathological changes and renal tissue protein expression were assayed.</p><p><strong>Results: </strong>Cell experiment showed that high glucose could induce epithelial-mesenchymal transition (EMT). After finerenone treatment, we accessed the EMT-related protein and found EMT was reversed. Besides, the cell migration capacity and cytoskeleton were also ameliorated. To further explore the mechanism, we found that finerenone could upregulate the expression of Krüppel-like factor 5 (KLF5) which was downregulated in a high glucose environment. After the silence of KLF5 in the presence of finerenone, the rescue experiment showed the protective function of finerenone is counteracted by KLF5. In animal experiment, after the treatment of finerenone, the level of blood creatinine decreased compared with the DN group while blood urea nitrogen (BUN) and potassium showed no significant difference. The pathological alterations of the treatment group also got ameliorated. Finerenone could normalize the level of EMT-related protein, nephrin, and KLF5 of kidney tissue in DN rats.</p><p><strong>Conclusion: </strong>Our results suggest that finerenone could alleviate high glucose-induced podocyte EMT via regulating KLF5. Further investigation is warranted to elucidate the precise underlying mechanism.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"637-651"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of <i>KCNJ11</i> E23K/rs5219 Gene Polymorphism with Type 2 Diabetes and Diabetes-Related Cardiovascular Disease.","authors":"Monika Buraczynska, Sylwia Boczkowska, Wojciech Zaluska","doi":"10.2147/DMSO.S506639","DOIUrl":"10.2147/DMSO.S506639","url":null,"abstract":"<p><strong>Objective: </strong>A potassium voltage-gated channel subfamily J member 11 (<i>KCNJ11</i>) is a candidate gene for diabetes and cardiovascular disease. We investigated the relationship of <i>KCNJ11</i> E23K gene polymorphism with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease (CVD).</p><p><strong>Methods: </strong>In this case-control study, the <i>KCNJ11</i> E23K (rs5219) single nucleotide polymorphism was evaluated using the PCR-RFLP method in 780 patients with T2DM and 425 healthy controls. The genotype distribution was compared between subgroups of patients with CVD (524) and without CVD (256).</p><p><strong>Results: </strong>The genotyping results showed that the T allele and TT genotype were associated with the risk of T2DM (OR 1.26, p = 0.008 and OR 1.55, p = 0.0019, respectively). The T2DM group was analyzed according to the presence or absence of CVD. The T allele frequency was significantly higher in CVD+ than CVD- patients (49% vs 28%, p = 0.0001). The frequency of TT genotype in CVD+ subgroup was 20% compared to 8.5% in CVD-. This shows the significant correlation of the T allele with CVD in T2DM patients in all genetic association models. The OR for T allele was 2.44, p < 0.0001 representing 2.5-fold higher odds of CVD. For TT genotype, the OR 5.61, p < 0.0001 represents almost 6-fold higher risk of CVD development. The multiple logistic regression analysis showed that <i>KCNJ11</i> E23K polymorphism was a significant risk predictor for CVD development (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong>This is the first study of the relationship between <i>KCNJ11</i> gene polymorphism and cardiovascular risk in T2DM patients in Polish population. The E23K (rs5219) polymorphism is associated with T2DM. It also increases the risk of cardiovascular disease in T2DM patients. If confirmed in other studies, it can be considered a potential marker for predicting the risk of CVD in T2DM patients.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"653-661"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Effect of Acute Elevated Intraocular Pressure on Retinal and Choroidal Microvasculature in Diabetic Rats.","authors":"Yao Yao, Yanni Yan, Wenbin Wei, Qian Wang","doi":"10.2147/DMSO.S493984","DOIUrl":"10.2147/DMSO.S493984","url":null,"abstract":"<p><strong>Purpose: </strong>Understanding the dynamics of blood flow regulation in diabetic conditions is crucial for developing targeted interventions. This study aimed to investigate the impact of acute intraocular pressure (IOP) elevation on retinal and choroidal microvasculature in diabetic and control rats.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were divided into two groups: diabetic and control. Acute IOP elevation was achieved through controlled perfusion pressure. Retinal and choroidal blood flow was measured using Swept-Source Optical Coherence Tomography Angiography (SS-OCT/OCTA).</p><p><strong>Results: </strong>At baseline IOP levels, there were no statistically significant differences in perfusion area (PA) between the two groups in all regions of the retina and choroid. During acute IOP elevation, both diabetic and control rats experienced a significant reduction in retinal and choroidal blood flow perfusion. Diabetic rats manifested significantly higher (P<0.05) alterations in PA across nearly all retinal regions compared to the control group, barring specific sub-regions of the outer ring. Concerning choroidal PA, the diabetic group exhibited a more pronounced alteration than the control group across the entire 6-mm region and certain sub-regions of the outer ring.</p><p><strong>Conclusion: </strong>Our results demonstrate a clear association between diabetes and impaired choroidal vascular autoregulation during acute IOP elevation. The observed reduction in retinal and choroidal microvasculature in diabetic rats points towards a compromised ability to maintain blood flow homeostasis under stress conditions.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"615-625"},"PeriodicalIF":2.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of MR Spectroscopy, 2-Point Dixon, and Multi-Echo T2* Sequences in Assessing Hepatic Fat Fraction Across a Diverse Range of Body Mass Index (BMI) and Waist Circumference Ratio (WCR) Values.","authors":"Beata Brzeska, Agnieszka Sabisz, Oliwia Kozak, Edyta Szurowska, Joanna Pieńkowska","doi":"10.2147/DMSO.S481062","DOIUrl":"10.2147/DMSO.S481062","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to compare and evaluate the accuracy of three magnetic resonance imaging (MRI) sequences-MR liver spectroscopy, 2-point Dixon, and multi-echo T2*-in assessing hepatic fat fraction in patients with various body mass indexes (BMIs).</p><p><strong>Methods: </strong>167 participants were recruited, including 110 healthy subjects with diverse BMIs and 57 bariatric surgery candidates. The MRI protocol involved three sequences: multi-echo single voxel STEAM 1H spectroscopy, 2-point mDixon, and multi-echo T2* sequence. Hepatic fat fraction was measured using these sequences and analyzed statistically to determine correlations and agreement between the methods.</p><p><strong>Results: </strong>A strong positive correlation was observed between BMI and waist circumference ratio (WCR) (r_s(165) = 0.910, p<0.001). MRS obtained hepatic fat fraction numerical values in 13.33% of the normal BMI group, 48.48% of the overweight group, and 72.97% of the obese group. Strong correlations were found between all methods, with significant agreement, particularly between MRS and multi-echo T2*.</p><p><strong>Conclusion: </strong>Robust correlations were observed between MR spectroscopy, 2-point Dixon, and multi-echo T2* methods for liver fat fraction measurement, especially in patients with higher BMI and WCR. These findings highlight the importance of BMI and WCR in interpreting fat fraction measurements, as method performance can vary across body composition profiles.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"601-614"},"PeriodicalIF":2.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of the Effects of Shenzhu Tiaopi Granules on Model Rats with Type 2 Diabetes Mellitus.","authors":"Jin-Dong Zhao, Zhao-Hui Fang","doi":"10.2147/DMSO.S493036","DOIUrl":"https://doi.org/10.2147/DMSO.S493036","url":null,"abstract":"<p><strong>Background: </strong>Shenzhu Tiaopi granule (STG) has antidiabetic functions. Data-independent acquisition proteomic technology is an integral part of systems biology. Herein, proteomics was used to analyse the effects of STG on type 2 diabetes mellitus (T2DM) and the mechanism by which STG normalizes glucose metabolism.</p><p><strong>Methods: </strong>Goto-Kakizaki (GK) T2DM model (Mod) rats, aged 15-16 weeks and with a fasting blood glucose (FBG) level of ≥11.1 mmol/L, were treated with metformin or STG for 12 weeks. Wistar rats aged 15-16 weeks were included in the control (Con) group. Body weight, FBG, total cholesterol (TC), total triglyceride (TG) levels and low-density lipoprotein (LDL-C) levels were measured, and pathological observation, Western blot analysis and data-independent acquisition proteomics of the liver were performed.</p><p><strong>Results: </strong>Significant differences in FBG, TC, TG, LDL-C (p < 0.01) and pathological liver morphology were observed between the Mod group and Con group, whereas both metformin and STG normalized the glucose and lipid metabolism indicators (p < 0.05 or p < 0.01). In total, 5856 proteins were identified via proteomic analysis, 97 of which were significantly differentially expressed in the liver and affected fatty acid metabolism, unsaturated fatty acid biosynthesis, the peroxisome proliferator-activated receptor (PPAR) signalling pathway, pyruvate metabolism, and terpenoid backbone biosynthesis. Screening identified 10 target proteins, including perilipin-2 (Plin2), pyruvate dehydrogenase kinase 4, farnesyl diphosphate synthase (Fdps) and farnesyl-diphosphate farnesyltransferase 1. Among these proteins, the key proteins were Plin2 and Fdps, which were found to be associated with the PPAR signalling pathway and terpenoid backbone biosynthesis via relationship networks. Plin2 and Fdps are closely related to hyperglycaemia. STG can downregulate Plin2 and upregulate Fdps (p < 0.01).</p><p><strong>Conclusion: </strong>STG ameliorated hyperglycaemia by significantly altering the expression of different proteins, especially Fdps and Plin2, in the livers of GK rats. These findings may reveal the potential of traditional Chinese medicine for treating T2DM.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"583-599"},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors for Gestational Diabetes Mellitus in Mainland China: A Systematic Review and Meta-Analysis.","authors":"Linjuan Xia, Zehua Yang, Qincai Mu, Yulin Ji, Juncheng Lyu","doi":"10.2147/DMSO.S502043","DOIUrl":"10.2147/DMSO.S502043","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify and evaluate risk factors associated with gestational diabetes mellitus (GDM) in mainland China.</p><p><strong>Methods: </strong>Eight electronic databases were searched for literature published from January 2010 until December 2023. Heterogeneity was quantified using I². Data were pooled by fixed or random effects models and expressed as odds ratio and 95% confidence intervals.</p><p><strong>Results: </strong>A total of 69 observational studies with an overall sample size of 2,138,032 Chinese women and 219,303 patients with GDM were included in the analysis. After adjusting confounders, older maternal age (OR = 1.12, 95% CI: 1.09-1.15), maternal age ≥35 years (OR = 1.96, 95% CI: 1.74-2.21), higher pre-pregnancy body mass index (OR = 1.24, 95% CI: 1.17-1.32), pre-pregnancy overweight (OR = 1.78, 95% CI: 1.64-1.92) or obesity (OR 2.52, 95% CI: 2.06-3.08), family history of diabetes (OR = 1.85, 95% CI: 1.58-2.17), history of GDM (OR = 4.09, 95% CI: 2.13-7.82), and elevated levels of fasting plasma glucose (OR = 2.54, 95% CI: 2.13-3.01), hemoglobin (OR = 1.47, 95% CI: 1.14-1.89) and serum triglycerides (OR = 1.69, 95% CI: 1.31-2.16) in early pregnancy were associated with an increased risk of GDM in mainland China. But gravidity ≥2 (OR = 1.06, 95% CI: 0.89-1.27), conception by assisted reproductive technology analyses (OR = 1.54, 95% CI: 0.95-2.51) were not associated with GDM, and parity ≥1 (OR = 0.88, 95% CI: 0.82-0.94) was related to lower risk of GDM. In available unadjusted studies, history of abortion (OR = 1.34, 95% CI: 1.31-1.37) increased risk of GDM, non-Han ethnicity (OR = 0.78, 95% CI: 0.59-1.03) and high school or lower education level (OR1.09, 95% CI: 0.94-1.26) showed no correlation with GDM.</p><p><strong>Conclusion: </strong>The key risk factors for GDM in mainland China included older maternal age, maternal age ≥35 years, pre-pregnancy overweight or obesity, family history of diabetes, history of GDM, elevated levels of FPG, Hb, and serum TG in early pregnancy. Early identification and intervention for women at high risk should be performed to prevent the development of GDM.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"565-581"},"PeriodicalIF":2.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Body Mass Index and Glycemic Control in Type 2 Diabetes Mellitus: A Cross-Sectional Study.","authors":"Li Deng, Long Jia, Xiao-Li Wu, Ming Cheng","doi":"10.2147/DMSO.S508365","DOIUrl":"10.2147/DMSO.S508365","url":null,"abstract":"<p><strong>Background: </strong>Body mass index (BMI) is a known risk factor for poor glycemic control in patients with Type 2 diabetes mellitus (T2DM). However, the extent to which BMI correlates with glycated hemoglobin (HbA1c) levels and its clinical implications require further investigation.</p><p><strong>Objective: </strong>This study aimed to assess the relationship between BMI and HbA1c levels in T2DM patients and to explore the clinical significance of BMI management in optimizing glycemic control.</p><p><strong>Methods: </strong>A cross-sectional study was conducted on 200 T2DM patients from Jinniu District Hospital between 2024/04/01 and 2024/10/03. BMI and HbA1c levels were recorded, and patients were categorized into normal weight (BMI < 25 kg/m²), overweight (25 ≤ BMI < 30 kg/m²), and obese (BMI ≥ 30 kg/m²). Pearson correlation analysis was used to assess the relationship between BMI and HbA1c. One-way ANOVA was employed to compare HbA1c levels across BMI categories.</p><p><strong>Results: </strong>A significant positive correlation between BMI and HbA1c was observed (r = 0.45, P < 0.001). Obese patients had significantly higher HbA1c levels (8.5 [7.8-9.0]%) compared to overweight (7.7 [7.2-8.1]%, P < 0.01) and normal-weight patients (6.9 [6.4-7.5]%, P < 0.001). The graded relationship indicated worsening glycemic control with increasing BMI.</p><p><strong>Conclusion: </strong>Higher BMI is associated with poorer glycemic control in T2DM patients. Obese patients, in particular, may benefit from more intensive weight management strategies to reduce HbA1c levels and prevent diabetes-related complications. These findings underscore the importance of integrating BMI reduction into diabetes management plans to improve clinical outcomes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"555-563"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Placental MFF-Mediated Mitochondrial Fission in Gestational Diabetes Mellitus.","authors":"Lijie Wei, Chenyun Fang, Yi Jiang, Huiting Zhang, Peng Gao, Xuan Zhou, Shenglan Zhu, Yuanyuan Du, Rui Su, Lili Guo, Mengzhou He, Shaoshuai Wang, Ling Feng, Jun Yu","doi":"10.2147/DMSO.S484002","DOIUrl":"10.2147/DMSO.S484002","url":null,"abstract":"<p><strong>Introduction: </strong>Gestational diabetes mellitus (GDM) refers to hyperglycemia first recognized during pregnancy, characterized by decreased insulin sensitivity and impaired glucose metabolism. Dynamic fusion and fission processes within mitochondria play critical roles in maintaining glucose metabolism homeostasis. Given the fundamental role of mitochondrial fission factor (MFF) in mitochondrial fission, the intention of this study was to investigate mitochondrial dynamics in the placentae of GDM patients and explore the role of MFF in the etiopathogenesis and progression of GDM through the modulation of glucose metabolism and insulin resistance.</p><p><strong>Methods: </strong>40 Placental tissues were obtained from pregnant women undergoing cesarean section with GDM (n=20) and those with normoglycemia (n=20). To mimic the intrauterine high glucose environment, immortalized human-derived first-trimester extravillous trophoblast cells HTR8/SVneo were used and treated in a high glucose environment. Immunofluorescence was utilized to analyze MFF expression in placental tissues and mitochondrial length in HTR8/SVneo cells. The expression levels of glucose transporters (GLUTs) and other pivotal proteins involved in mitochondrial dynamics and the insulin signaling pathway, were assessed by Western blotting. Additionally, cellular glucose uptake capacity was determined using a glucose assay kit.</p><p><strong>Results: </strong>MFF expression was greater in the GDM group than in the normoglycemic group. In a high-glucose environment, the expression of fusion-related proteins OPA1, MFN1 and MFN2 decreased while the expression of DRP1 and MFF increased, indicating that the mitochondrial dynamics of trophoblast cells shift toward fission. Elevated mitochondrial fission hinders the insulin signaling pathway, resulting in a reduction in glucose uptake by HTR8/SVneo cells and a concurrent decrease in GLUT4 expression.</p><p><strong>Discussion: </strong>Our study demonstrates that MFF-mediated mitochondrial fission inhibits insulin sensitivity and upregulates glucose transport in GDM, which is related to offspring exposure to a hyperglycemic intrauterine environment. These results provide a novel therapeutic target for addressing GDM that may mitigate unfavorable pregnancy outcomes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"541-554"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}