{"title":"Exploring the impact of glycemic variability on clinical outcomes in critically ill cerebral infarction patients.","authors":"Hui Yang, Hongcai Wang, Yan Jiang","doi":"10.1186/s13098-025-01676-x","DOIUrl":"10.1186/s13098-025-01676-x","url":null,"abstract":"<p><strong>Background: </strong>Glycemic variability (GV) is a key determinant of outcomes in critically ill patients, yet its impact on cerebral infarction patients in intensive care units (ICUs) remains underexplored. This study evaluates the association between GV and clinical outcomes, including discharge outcomes, 90-day and 1-year mortality, and ICU/hospital length of stay (LOS).</p><p><strong>Methods: </strong>This retrospective study of 778 cerebral infarction patients from the MIMIC-IV database assessed GV, calculated as the glucose standard deviation-to-mean ratio during ICU stays. Regression models evaluated GV's impact on discharge outcomes, mortality, and ICU/hospital LOS, with adjustments for confounders. Restricted cubic spline analyses identified risk thresholds, while sensitivity and subgroup analyses validated findings. Predictive performance was assessed using AUC, NRI, and IDI, and multiple imputation methods addressed missing data.</p><p><strong>Results: </strong>Higher GV was significantly linked to adverse outcomes. Patients in the highest GV quartile had increased risks of poor discharge outcomes (adjusted OR: 1.83; 95% CI: 1.03-3.32; P = 0.042), 90-day mortality (adjusted HR: 1.51; 95% CI: 1.03-2.22; P = 0.036), and 1-year mortality (adjusted HR: 1.53; 95% CI: 1.07-2.18; P = 0.018). RCS analysis identified critical GV thresholds (≥ 11% for 90-day and ≥ 10% for 1-year mortality). Subgroup analysis revealed stronger associations between GV and poor outcomes in non-diabetic patients (adjusted OR: 1.89; 95% CI: 1.24-2.88; P = 0.003) compared to diabetic patients (adjusted OR: 0.81; 95% CI: 0.53-1.25; P = 0.337). Sensitivity analyses confirmed the robustness of findings across imputation methods.</p><p><strong>Conclusions: </strong>GV independently predicts poor outcomes in ICU cerebral infarction patients. Integrating GV metrics into clinical workflows may improve risk stratification and guide interventions. Future research should validate these findings and explore strategies to reduce GV.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"100"},"PeriodicalIF":3.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699793","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 the interaction between interleukin-1β gene polymorphism and smoking status with the diabetic nephropathy risk in a Chinese Han population.","authors":"Tianyue Xie, Zhuqi Tang","doi":"10.1186/s13098-025-01667-y","DOIUrl":"10.1186/s13098-025-01667-y","url":null,"abstract":"<p><strong>Objectives: </strong>we aimed to evaluate the association of interleukin-1β (IL-1β) gene single nucleotide polymorphisms (SNPs) and its interaction with smoking status on diabetic nephropathy (DN) risk in a Chinese Han population.</p><p><strong>Methods: </strong>The Hardy-Weinberg equilibrium (HWE) was tested by using SNPStats ( https://www.snpstats.net/start.htm ), which was also used for testing the relationship between four SNPs and DN risk and haplotype analysis. The SNP- SNP and gene- smoking interaction were verified by using generalized multifactor dimensionality reduction (GMDR) model.</p><p><strong>Results: </strong>Logistic regression suggested that the DN risks of participants with rs16944- G allele were significantly higher than those with AA genotype, adjusted OR (95%CI) = 1.62 (1.24-2.01) for AG versus AA, 1.41 (0.75-2.12) for GG versus AA. Additionally, we also found that participants with rs3917356- T allele had an obviously higher DN risk than those with CC genotype, adjusted OR (95%CI) = 1.75 (1.34-2.19) for CT versus CC, 1.87 (1.23-2.54) for TT versus CC. GMDR model found a significant two-locus model (P = 0.011) including rs16944 and smoking. Compared with non- smokers with rs16944- AA genotype, smokers with rs1225404 AG or GG genotype had the highest DN risk after covariates adjustment, OR (95%CI) was 3.04 (1.98-4.12). We also found a haplotype containing rs1143634- T and rs3917356- T was associated with higher DN risk.</p><p><strong>Conclusions: </strong>we found that the rs16944- G and rs3917356- T allele, interaction between rs16944 and smoking, haplotype containing rs1143634- T and rs3917356- T were all associated with increased DN risk.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"101"},"PeriodicalIF":3.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699632","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}
Zikai Jin, Liming Zheng, Chuanrui Sun, Bo Xu, Xiangyun Guo, Yili Zhang, Linghui Li, Xu Wei
{"title":"More comprehensive relationship between eGDR and sarcopenia in China: a nationwide cohort study with national representation.","authors":"Zikai Jin, Liming Zheng, Chuanrui Sun, Bo Xu, Xiangyun Guo, Yili Zhang, Linghui Li, Xu Wei","doi":"10.1186/s13098-025-01657-0","DOIUrl":"10.1186/s13098-025-01657-0","url":null,"abstract":"<p><strong>Introduction: </strong>Although studies had shown that Insulin resistance (IR) was correlated with the occurrence of sarcopenia, there were still many controversial conclusions. Therefore, we conducted a more comprehensive study on the relationship between the estimated glucose disposal rate (eGDR), an alternative indicator of IR, and the risk of sarcopenia, muscle mass, and muscle strength to clarify their interactions.</p><p><strong>Methods: </strong>The Study included individuals from The China Health and Retirement Longitudinal Study (CHARLS) who had complete eGDR data at baseline and did not develop low muscle mass and low muscle strength. The individuals were divided into four subgroups based on the quartile (Q) of the eGDR. The lowest quartile (Q1) of the eGDR was used as a reference. Logistic regression and linear regression were used to evaluate the relationship between eGDR and sarcopenia (low muscle mass, low muscle strength, possible sarcopenia, and sarcopenia) and sarcopenia related features (ASM/Ht2, grip, and RMS), respectively. In addition, we further evaluated the nonlinear relationship using smooth curve fitting and threshold effect analysis.</p><p><strong>Results: </strong>The results showed that after adjusting for confounders, eGDR was negatively associated with the risk of sarcopenia and positively associated with sarcopenia related characteristics. In addition, men showed a more significant reduction in the likelihood of low muscle mass compared to women. But as eGDR levels rise, women gain more ASM/Ht<sup>2</sup>. Further nonlinear analysis revealed an inverse correlation between eGDR and ASM/Ht<sup>2</sup> at the inflection point of 15.3893. Besides that, eGDR was positively correlated with grip (7.1862) and RMS (11.1042) before the inflection point.</p><p><strong>Conclusions: </strong>The study found that higher levels of eGDR were associated with a lower risk of developing sarcopenia. However, the effects of eGDR on muscle mass and muscle strength need to be considered comprehensively. For muscle mass, it is recommended to maintain eGDR below 15.3893, and for muscle strength, it is recommended to maintain eGDR below 7.1862, with more potential benefits for early warning of sarcopenia.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"97"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691146","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 association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the risk of ischemic heart disease in type 2 diabetes mellitus participants: a large-scale cohort study from the UK Biobank.","authors":"Sikun Zhang, Zhaowei Zhu","doi":"10.1186/s13098-025-01646-3","DOIUrl":"10.1186/s13098-025-01646-3","url":null,"abstract":"<p><strong>Background: </strong>The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid indicator used for assessing the risk of cardiovascular diseases. This study was performed to explore the association between NHHR and the risk of ischemic heart disease (IHD) in type 2 diabetes mellitus (T2DM) patients.</p><p><strong>Methods: </strong>This large-scale prospective cohort study included 19,925 participants from the UK Biobank. Cox proportional hazards regression models were used to assess the association between the NHHR and the risk of IHD in T2DM participants and restricted cubic spline (RCS) analysis was conducted to assess the dose-response association. Subgroup analysis and several sensitivity analyses were carried out to examine the robustness of our findings.</p><p><strong>Results: </strong>During the follow-up (median 12.7 years), 3,600 T2DM participants developed IHD. The association between the NHHR and the risk of IHD in T2DM participants was significant in the highest NHHR quartile (quartile 4), whereas this association was not stable in quartile 2 or quartile 3. Four sensitivity analyses showed similar results. RCS analysis did not reveal a significant nonlinear relationship between the NHHR indicator and the risk of IHD in T2DM participants (P for nonlinearity = 0.9490). In the subgroup analysis, drinking status was found to have a joint effect with the NHHR on the incidence of IHD in T2DM patients (P for interaction = 0.038).</p><p><strong>Conclusions: </strong>A high level of NHHR is associated with a high risk of IHD in T2DM patients, indicating the great importance of using NHHR in the lipid management of T2DM patients.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"99"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699800","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}
Xiaowan Li, Liyan Zhang, Yingying Du, Yiru Shen, Yuanzhi Gong, Junjie Wang, Juan Zhou, Sheng Wang
{"title":"Association between monocyte-to-lymphocyte ratio and cardiovascular diseases: insights from NHANES data.","authors":"Xiaowan Li, Liyan Zhang, Yingying Du, Yiru Shen, Yuanzhi Gong, Junjie Wang, Juan Zhou, Sheng Wang","doi":"10.1186/s13098-025-01640-9","DOIUrl":"10.1186/s13098-025-01640-9","url":null,"abstract":"<p><strong>Background: </strong>This study intends to examine any possible correlation between monocyte-to-lymphocyte ratio (MLR) and cardiovascular diseases (CVD).</p><p><strong>Methods: </strong>Data from the 1999-2020 National Health and Nutrition Examination Survey (NHANES) in the USA were analyzed. Heart attacks, angina pectoris, congestive heart failure (CHF), coronary heart disease (CHD), and stroke were all covered by CVD. The independent relationships between these cardiovascular events and MLR levels, as well as other inflammatory indices (system inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), and C-reactive protein-to-albumin ratio (CAR)), were investigated. Furthermore, interaction tests and subgroup analysis were performed. Diagnostic capacities were also predicted and compared using receiver operating characteristic (ROC) curves.</p><p><strong>Results: </strong>Males made up 49.63% of the 46,289 people who were recruited in this study. The prevalence of CVD and its events were as follows: CHF at 2.99%, CHD at 3.72%, angina pectoris at 2.57%, heart attacks at 3.94%, and stroke at 3.48%, with CVD itself at 7.98%. MLR and CVD were positively correlated. Specifically, smooth curve fittings also found a non-linear relationship between MLR and CVD. Moreover, higher MLR levels were linked to increased rates of CHF, CHD, and strokes. SIRI was also found to have a positive correlation with CVD. MLR outperformed other inflammatory indices (SIRI, AISI, and CAR) in terms of discriminative capacity and accuracy in predicting CVD, CHF, CHD, angina pectoris, heart attack, and stroke, according to ROC analysis.</p><p><strong>Conclusions: </strong>Compared with other inflammatory indicators (SIRI, AISI, and CAR), MLR appears to be a better inflammatory index for predicting CVD, CHF, CHD, angina pectoris, heart attack, and stroke. American adults with elevated MLR and SIRI should be aware of the possible harm caused by CVD. Causal inference is, however, limited by the cross-sectional design and dependence on self-reported data. Further longitudinal studies are needed to validate these findings.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"98"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699539","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 renal function and diabetic retinopathy: a mediation analysis of geriatric nutritional risk index.","authors":"Youran Cai, Wanlu Qiu, Xiao Ma, Yuanting Yang, Ting Tang, Yuying Dong, Jian Chen, Qing Zhou","doi":"10.1186/s13098-025-01658-z","DOIUrl":"10.1186/s13098-025-01658-z","url":null,"abstract":"<p><strong>Background: </strong>Diabetes retinopathy (DR) is a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). This study investigated the correlation between renal function and DR, as well as the potential mediating role of the geriatric nutritional risk index (GNRI).</p><p><strong>Method: </strong>We classified 1122 adults with T2DM aged ≥ 40 years from the National Health and Nutrition Examination Survey database (2005-2008) into 2 groups: those with DR and those without DR. We used multivariate logistic regression analysis and restricted cubic spline (RCS) model to explore the relationship between renal function indicators and DR. Additionally, we analyzed the mediating impact of GNRI on renal function and DR.</p><p><strong>Result: </strong>After accounting for all covariates, the weighted multivariate analysis revealed significant associations between renal function markers and DR. Specifically, creatinine, albumin, blood urea nitrogen, and serum uric acid to creatinine ratio (SUACr) were significantly correlated with DR in serum examination, while creatinine was the only marker correlated with DR in urine. GNRI was negatively correlated with DR (odds ratio 0.94, 95% CI 0.92-0.99). Weighted linear regression showed a negative association between SUACr and GNRI (β = 0.37; 95% CI 0.12-0.62). The RCS analysis showed a nonlinear association between serum creatinine and DR (P<sub>non-linear</sub> = 0.013). GNRI mediated 14.4% of the relationship between SUACr and DR.</p><p><strong>Conclusion: </strong>Our study adds to previous research by analyzing the associations between renal function indicators and DR. Furthermore, we highlight the mediating effect of GNRI, suggesting its potential utility as a predictive and treatment index for assessing renal function and DR.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"95"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676773","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}
Janet M Wojcicki, Elissa Epel, Jue Lin, Viva Tai, Jean-Marc Schwarz, Susan M Noworolski, Ayca Erkin-Cakmak, Kathleen Mulligan, Alejandro Gugliucci, Rob H Lustig
{"title":"Leukocyte telomere length change in children with obesity in the context of an isocaloric fructose restriction intervention.","authors":"Janet M Wojcicki, Elissa Epel, Jue Lin, Viva Tai, Jean-Marc Schwarz, Susan M Noworolski, Ayca Erkin-Cakmak, Kathleen Mulligan, Alejandro Gugliucci, Rob H Lustig","doi":"10.1186/s13098-025-01611-0","DOIUrl":"10.1186/s13098-025-01611-0","url":null,"abstract":"<p><strong>Background: </strong>Few studies have evaluated changes in leukocyte telomere length (LTL) over a short time period (e.g. 1 week). LTL shortening is accelerated by exposure to inflammation and reactive oxygen species (ROS) damage.</p><p><strong>Methods: </strong>In the context of an isocaloric fructose restriction study that was conducted with 43 Black and Latinx children over a 9-day period, we evaluated the relationship between metabolic health at baseline and metabolic changes and LTL at baseline and %LTL change over the follow-up period. Linear regression models were used to assess associations between metabolic correlates and LTL at baseline and LTL changes over 9 days.</p><p><strong>Results: </strong>Overall children lost - 0.05 ± 0.14 T/S units or - 2.98 ± 8.74% total change over the follow-up period. Higher concentrations of HDL-C, APO-AI and a greater % of large HDL-C at baseline were associated with reduced LTL attrition rates at day 10 (p < 0.01; p < 0.01 and p = 0.02 respectively). Increases in APO-AI over the follow-up period were associated with increased LTL attrition over the follow-up period (p = 0.03).</p><p><strong>Conclusions: </strong>In this short term isocaloric fructose restriction study, LTL at baseline and changes in LTL over 9 days were associated with HDL-C and APO-AI and not with any other non-HDL-C lipids. Additional, larger studies are necessary to better understand the interplay between short term fructose restriction, LTL changes and HDL-C/APO-AI.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"94"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676766","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 the Triglyceride-glucose index and fragility fractures among US adults: insights from NHANES.","authors":"Yuan Lou, Huan Chen, Fuli Man, Lina Zhang, Qi Pan","doi":"10.1186/s13098-025-01669-w","DOIUrl":"10.1186/s13098-025-01669-w","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index, a recognized marker for insulin resistance, holds potential implications for skeletal health. However, its relationship with fragility fractures remains uncertain. We aimed to elucidate the association between the TyG index and fragility fractures in the general US population.</p><p><strong>Methods: </strong>Cross-sectional data of 25,082 participants were obtained from the National Health and Nutrition Examination Survey. The association between the TyG index and fragility fractures was investigated using univariate and weighted multivariate logistic regression as well as restricted cubic spline (RCS) regression models. The least absolute shrinkage and selection operator regression with ten-fold cross-validation was employed to identify key variables, leading to the development of a nomogram model. Calibration and receiver operating characteristic curves were utilized to evaluate the model's validity.</p><p><strong>Results: </strong>The overall prevalence of fragility fractures among participants was 1.10%. After adjusting for confounders, the TyG index exhibited a robust association with the risk of fragility fractures (odds ratio, 1.94; 95% confidence interval, 1.31-2.88; P < 0.001). RCS regression demonstrated a positive linear relationship between the TyG index and fragility fractures. The predictive nomogram, incorporating the TyG index and other clinical factors, demonstrated favorable predictive performance (consistency index = 0.901).</p><p><strong>Conclusions: </strong>Elevated TyG index levels were significantly correlated with the risk of fragility fractures in the general US population. These findings suggest that the TyG index may serve as a predictive marker for fragility fractures, underscoring the importance of early intervention and improved fracture risk assessment tools in clinical practice.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"96"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676777","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}
Hui Song, Jiarui Li, Haohao Yang, Bin Kong, Yu Xu, Xiong Li, Hui Li
{"title":"Enhancement of functional insulin-producing cell differentiation from embryonic stem cells through MST1-silencing.","authors":"Hui Song, Jiarui Li, Haohao Yang, Bin Kong, Yu Xu, Xiong Li, Hui Li","doi":"10.1186/s13098-025-01666-z","DOIUrl":"10.1186/s13098-025-01666-z","url":null,"abstract":"<p><strong>Background: </strong>Islet β-cell transplantation offers a promising treatment for repairing pancreatic damage in diabetes, with the transcription factor pancreatic duodenal homeobox-1 (PDX1) being crucial for β-cell function and insulin secretion. Mammalian threonine protein kinase (MST1) is recognized for its role in regulating PDX1 during cell apoptosis, yet its function in embryonic stem cell (ESC) differentiation into insulin-producing cells (IPCs) remain underexplored. This study investigated the effect of MST1-silencing on the differentiation of ESC into IPCs.</p><p><strong>Methods: </strong>ESCs were transfected utilizing a recombinant MST1-silencing lentiviral vector (shMST1). qRT-PCR, immunofluorescence, flow cytometry, western blot and ELISA assays were performed to examine function of IPCs in vitro. Furthermore, these IPCs were transplanted into type 1 diabetic mellitus (T1DM) rats. Measuring the changes in blood glucose concentration of animals before and after IPCs transplantation. Intraperitoneal glucose tolerance test (IPGT) was used to determine the regulatory effect of IPCs transplantation on blood glucose stimulation and immunohistochemistry was used to detect the expression of pancreatic Insulin protein in T1DM rats.</p><p><strong>Results: </strong>It was observed that IPCs from the shMST1 group exhibited notably improvement in insulin secretion and glucose responsiveness, suggesting MST1 suppression may enhance IPC maturity. The rats demonstrated significant normalization of blood sugar levels and increased insulin levels, akin to non-diabetic controls. This implies that MST1-silencing not only augments IPC function in vitro but also their therapeutic efficacy in vivo.</p><p><strong>Conclusions: </strong>The findings indicate that targeting MST1 offers a novel approach for deriving functionally mature IPCs from ESCs, potentially advancing cell replacement therapies for diabetes. This research underscores the importance of developing IPCs with competent insulin secretion for diabetes treatment in vitro.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"93"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662989","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}
Hiba S Al-Amodi, Nazik Altayeb Abdelbasit, Sameer H Fatani, Mohiuddin M Taher, Maowia Mohamed Mukhtar, Ayman S Mohamed, Abdallah M Gameel, Hala F M Kamel, Shimaa Abdelsattar
{"title":"Identification of variants in exon 4 of the LDLR gene and assessment of their effects on the produced proteins in saudi women with metabolic syndrome.","authors":"Hiba S Al-Amodi, Nazik Altayeb Abdelbasit, Sameer H Fatani, Mohiuddin M Taher, Maowia Mohamed Mukhtar, Ayman S Mohamed, Abdallah M Gameel, Hala F M Kamel, Shimaa Abdelsattar","doi":"10.1186/s13098-025-01650-7","DOIUrl":"10.1186/s13098-025-01650-7","url":null,"abstract":"<p><strong>Background: </strong>Genetic factors might influence metabolic syndrome (MetS) or any of its components. It was postulated that low density lipoprotein receptor (LDLR) gene variants could play a role in cholesterol hemostasis and the development of MetS. However, the causal-effect relationship between such variants and the development of MetS is not clearly identified or even studied before in Saudi Arabian women. This study aims to identify the variants of LDLR exon-4 in Saudi Arabian women with MetS in comparison to healthy women and to assess the expected effect of amino acids alterations on the structure and functions of the LDLR proteins. A total of 208 female Saudi patients with MetS and 104 controls were included in the study. The exon 4 of LDLR gene was studied by DNA sequencing (Sanger) and structural analysis was performed using Project HOPE software.</p><p><strong>Results: </strong>Four variants were identified; 2 were missense variants (2.4%; 5/208): (p.D172N and p.D178N) and 2 were nonsense variants (stop gained) (1.44%; 3/208): (p.E140* and p.L135*). Structural analysis of the expected effects of such variants revealed that they might disrupt their interactions with other proteins or biomolecules, additionally, the nonsense variants via expressing a stop codon, these will produce a truncated protein resulting in a defective function of LDL receptor.</p><p><strong>Conclusions: </strong>Four variants in the LDLR gene, exon 4 (2 missense and 2 nonsense variants) have been identified and their expected structural effects were assessed in Saudi Arabian women with MetS in Makkah region.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"91"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662990","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}