{"title":"Metformin and the risk of malignant tumors of digestive system: a mendelian randomization study.","authors":"Ping Liu, Junqi Xiao, Jinghuang Xiao, Jumei Zhou","doi":"10.1186/s13098-024-01573-9","DOIUrl":"https://doi.org/10.1186/s13098-024-01573-9","url":null,"abstract":"<p><strong>Background: </strong>Observational studies suggest that metformin may reduce the risk of malignant tumors of the digestive system (MTDS), but these findings are often confounded by bias and unmeasured variables. Recent meta-analyses have questioned these associations, emphasizing the need for robust causal inference.</p><p><strong>Methods: </strong>Mendelian randomization (MR) was used to evaluate the causal relationship between metformin and MTDS. Genetic variants associated with metformin's molecular targets were selected from GTEx, eQTLGen, and UK Biobank and validated using genetic colocalization to ensure instrument validity. GWAS summary statistics for MTDS, encompassing up to 314,193 controls and 6,847 colorectal cancer cases, were obtained from FinnGen and EBI. The primary analysis employed the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode analyses. Bonferroni correction was applied to adjust for multiple testing across 14 cancer types.</p><p><strong>Results: </strong>Genetically proxied metformin use was associated with an increased risk of colorectal cancer (OR = 2.38, 95%CI = 1.38-4.09, P = 0.0018) and related subtypes. No causal relationship was found for hepatocellular carcinoma, gastric cancer, pancreatic cancer, or other digestive system cancers. The robustness of these findings was supported by sensitivity analyses, which indicated no significant pleiotropy, and leave-one-out tests.</p><p><strong>Conclusion: </strong>This study provides robust genetic evidence that metformin use increases the risk of colorectal cancer, challenging its role as a preventive agent for digestive cancers. These findings emphasize the need for clinicians to carefully evaluate the risks and benefits of metformin, particularly in populations at higher risk for colorectal cancer. Future research should focus on delineating the mechanisms underlying this association to optimize the use of metformin in clinical practice.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"6"},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946236","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}
Mohamed A Abu Elainein, Mohamad Mahmoud Whdan, Mahmoud Samir, Nada G Hamam, Mohamed Mansour, Mohamed Abdel Mohsen Mohamed, Mahmoud Mostafa Snosy, Mahmoud Ayman Othman, Ahmed Sayed Sobieh, Mahmoud Gamal Saad, Mohamed A Labna, Salma Allam
{"title":"Therapeutic potential of adipose-derived stem cells for diabetic foot ulcers: a systematic review and meta-analysis.","authors":"Mohamed A Abu Elainein, Mohamad Mahmoud Whdan, Mahmoud Samir, Nada G Hamam, Mohamed Mansour, Mohamed Abdel Mohsen Mohamed, Mahmoud Mostafa Snosy, Mahmoud Ayman Othman, Ahmed Sayed Sobieh, Mahmoud Gamal Saad, Mohamed A Labna, Salma Allam","doi":"10.1186/s13098-024-01523-5","DOIUrl":"https://doi.org/10.1186/s13098-024-01523-5","url":null,"abstract":"<p><strong>Background: </strong>As the global prevalence of diabetes mellitus increases, the incidence of non-healing wounds in diabetic patients is expected to rise significantly, according to the International Diabetes Federation (IDF), around 537 million adults currently suffer from diabetes mellitus worldwide and 20% to 30% of individuals with diabetes are hospitalized due to diabetic foot ulcers. Conventional treatments such as traditional dressings often fall short in ensuring satisfactory wound healing, this Meta-analysis investigates the therapeutic potential of Adipose-derived Stem Cells (ADSCs) as a promising strategy for addressing this challenge.</p><p><strong>Aims: </strong>To Assess the Therapeutic Potential of Adipose-Derived Stem Cells for Managing Diabetic Foot Ulcers compared to conventional lines of treatments.</p><p><strong>Methods: </strong>The PubMed, SCOPUS, Web of Science Core Collection, Cochrane Library, and ClinicalTrials.gov. databases were searched from January 2000 and December 2023, articles were primarily evaluated regarding their titles and abstracts, then full-text screening was assessed against the inclusion and exclusion criteria by utilizing Rayyan software. The Cochrane risk of bias (RoB 2) assessment tool was used to identify the risk of bias in our included studies. A statistical analysis was performed using Review Manager (RevMan) Version 5 software. Dichotomous data was subjected to risk ratio analysis, while continuous data underwent Mean Difference (MD) evaluation, all was reported with 95% confidence intervals, P value is considered statistically significant if less than 0.05.</p><p><strong>Results: </strong>Regarding the total healing state, five studies reported that more participants healed completely at the end of the follow-up period in the ADSCs group (Risk ratio = 1.56, 95% CI [1.32, 1.86], P < 0.00001), for the healing rate the overall effect estimate favors the ADSCs group (pooled effect estimate = 1.84, 95% CI [1.51, 2.89], P < 0.00001), and regarding the healing time the pooled mean difference of the studies demonstrated that the ADSCs group required fewer days to heal than the standard care group. (pooled mean difference = -19.33, 95% CI [-37.36, -1.29], P = 0.04).</p><p><strong>Conclusion: </strong>ADSCs provide favorable healing results and safety compared to standard care for diabetic foot ulcers.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"9"},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946248","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":"Insulin resistance as a mediator in the association between nickel exposure and metabolic dysfunction-associated steatotic liver disease.","authors":"Zhou Liu, Liang Zhang, Yanrui Wu, Zongbiao Tan, Guang Li, Zhenwen Li, Liying Zhan, Weiguo Dong","doi":"10.1186/s13098-024-01567-7","DOIUrl":"https://doi.org/10.1186/s13098-024-01567-7","url":null,"abstract":"<p><strong>Background: </strong>The myriad implications of heavy metal pollution on human health have garnered substantial attention within the academic domain. Nevertheless, a notable research gap persists, as there is currently insufficient direct investigation elucidating the intricate interplay between nickel exposure and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>The data utilized in this study was sourced from the National Health and Nutrition Examination Survey 2017-2020. Hepatic steatosis was evaluated utilizing controlled attenuation parameters (CAP), and nickel exposure level was reflected by urinary nickel concentration. To analyze the association between nickel exposure and MASLD, three multiple logistic regression models with weights were developed. Furthermore, a mediation analysis was performed to examine insulin resistance's potential mediating role.</p><p><strong>Results: </strong>There were a total of 1,187 participants in the study, of which 548 (46.17%) had MASLD. MASLD individuals had a significantly higher urinary nickel concentration than non-MASLD individuals (P = 0.008). After accounting for demographic factors, biochemical indicators, and metabolic conditions, the odds ratio (OR) and 95% confidence interval (CI) for MASLD were 2.10 (1.09-4.05) per onefold increase in urinary nickel concentration and 2.61 (1.22-5.55) for the highest tertile versus the lowest tertile. Insulin resistance was found to mediate approximately 73.69% of the total association between nickel exposure and MASLD (P = 0.004).</p><p><strong>Conclusions: </strong>Nickel exposure was independently associated with the prevalence of MASLD. Excessive exposure to nickel may promote the occurrence of MASLD by enhancing insulin resistance.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"8"},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946225","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":"Interaction between dipeptidyl-peptidase-4 inhibitors and drugs acting on renin angiotensin aldosterone system for the risk of angioedema: a pharmacovigilance assessment using disproportionality and interaction analyses.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.1186/s13098-024-01570-y","DOIUrl":"https://doi.org/10.1186/s13098-024-01570-y","url":null,"abstract":"<p><strong>Background: </strong>Dipeptidyl peptidase-4 inhibitors (DPP-4is) and drugs interfering with the renin-angiotensin-aldosterone system (RAAS) are frequently co-prescribed in type 2 diabetes management. Both drug classes have been independently associated with angioedema, raising concerns about potential interaction risks. This study aimed to evaluate the safety signals and interaction patterns for angioedema associated with DPP-4is alone and in combination with RAAS-interfering drugs.</p><p><strong>Methods: </strong>We conducted a comprehensive pharmacovigilance analysis using the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) database. Disproportionality analyses employing both frequentist (Reporting Odds Ratio, Proportional Reporting Ratio) and Bayesian approaches were performed. Drug-drug interactions were assessed using multiplicative drug-drug interaction model. Additionally, we reviewed published case reports of DPP-4i-associated angioedema.</p><p><strong>Results: </strong>Analysis of 29,163,222 reports identified 588 cases of DPP-4i-associated angioedema. Significant safety signals were detected for DPP-4i monotherapies, while combinations with RAAS-interfering drugs demonstrated stronger signals through both frequentist and Bayesian analyses. Significant interaction signals were observed for sitagliptin/irbesartan, sitagliptin/valsartan, linagliptin/valsartan and alogliptin/lisinopril combinations. Alogliptin/lisinopril and sitagliptin/irbesartan combinations showed the highest risk profiles. Angioedema occurred predominantly in elderly patients (> 65 years) and females. Sixteen case reports corroborated the findings from the database assessment. Clinical outcomes were comparable between monotherapy and combination therapy groups.</p><p><strong>Conclusion: </strong>This pharmacovigilance analysis reveals significant safety signals for angioedema with specific DPP-4i combinations with RAAS-interfering drugs, suggesting potential drug-drug interactions. These findings emphasize the need for careful patient monitoring, particularly in vulnerable populations, when prescribing these combinations. Further prospective studies are warranted to validate these findings and establish definitive causal relationships.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"7"},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946228","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":"Effects of exercise intensity and diet on cardiac tissue structure and FGF21/β-Klotho signaling in type 2 diabetic mice: a comparative study of HFD and HFD + STZ induced type 2 diabetes models in mice.","authors":"Sevda Moharamzadeh, Majid Kashef, Mojtaba Salehpour, Meysam Torabi, Samira Vesali, Zakieh Samsonchi, Ensiyeh Hajizadeh-Saffar","doi":"10.1186/s13098-024-01541-3","DOIUrl":"https://doi.org/10.1186/s13098-024-01541-3","url":null,"abstract":"<p><strong>Background: </strong>Structural heart disease is one of the leading causes of death in people with type 2 diabetes (T2D), which is not known to have an effect on exercise training. The aim of this study was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on heart tissue structure, the serum level of FGF21 and the heart tissue level of β-Klotho, an FGF21 coreceptor, in HFD and HFD + STZ-induced diabetic mice.</p><p><strong>Methods: </strong>Thirty-six male C57BL/6J mice were divided into high-fat diet (HFD) and normal chow diet (ND) groups. After 20 weeks of diet, the HFD mice were divided into HFD and HFD + STZ groups, and the latter group was injected with STZ. Then, the mice in the ND, HFD and HFD + STZ groups were divided into three subgroups of control (C), HIIT and MICT, and mice were placed in one of nine groups ND-C, ND-HIIT, ND-MICT, HFD-C, HFD-HIIT, HFD-MICT, HFD + STZ-C, HFD + STZ-HIIT, and HFD + STZ-MICT. The mice in the exercise training (ET) groups were run on a treadmill for eight weeks. Finally, the tissue and serum samples were collected and analyzed by two-way ANOVA.</p><p><strong>Results: </strong>Statistical analyses showed that the main effect of diabetes inducing model (DIM) was significant for all variables (p < 0.05), except vascular density (p = 0.055); the main effect of ET type on fasting blood glucose and FGF21 was significant (p < 0.001); and the interaction was significant for fasting blood glucose, heart weight and FGF21 (p < 0.001). Post hoc and subgroup analysis showed a superior effect of MICT over HIIT in decreasing fasting blood glucose and serum level of FGF21 (p < 0.001). Additionally, the results of the myocardial tissue qualitative analyses differed between the diabetic mouse models and the ET groups.</p><p><strong>Conclusions: </strong>In a mouse model, type 2 diabetes can negatively affect heart tissue structure and FGF21 signaling in cardiac tissue, and both HIIT and MICT can prevent this effect. However, MICT likely more effective that HIIT in reducing circulating FGF21.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"4"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min-Jia Cao, Ting-Ting Liang, Li Xu, Fang-Hong Shi
{"title":"Evaluating the overall renal outcomes of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD).","authors":"Min-Jia Cao, Ting-Ting Liang, Li Xu, Fang-Hong Shi","doi":"10.1186/s13098-024-01547-x","DOIUrl":"https://doi.org/10.1186/s13098-024-01547-x","url":null,"abstract":"<p><strong>Background: </strong>Our meta-analysis fills gaps by assessing sodium-glucose cotransporter-2 (SGLT2) inhibitors' renal outcomes in chronic kidney disease (CKD) patients including long-term effects and the subgroup analyses of estimated glomerular filtration rate (eGFR) values and follow-up times.</p><p><strong>Methods: </strong>The literature search of relevant randomized controlled trials (RCTs) was conducted in Medline, Embase, and the Cochrane Central from the inception to 8 June 2023 on patients with CKD treated with SGLT2 inhibitors. We selected medical subject heading (MeSH) terms and free text terms associated with gliflozin and RCT. We calculated odds ratio (OR) or harzard ratio with 95% confidence intervals (CIs) for composite outcomes and dichotomous data, and weighted mean differences (WMD) for changes in eGFR.</p><p><strong>Results: </strong>16 RCTs enrolling 52,306 patients were in the final population, with 26,910 being treated with SGLT2 inhibitors and 25,396 serving as controls were identified. We found that there was no decline in the rate of change in eGFR after 13 weeks and SGLT2 inhibitors treatment significantly improved the rate of change in eGFR after 64 weeks (64-104 weeks: WMD, 1.024 mL/min/1.73m<sup>2</sup>/per year, 95% CI 0.643-1.406; 104 weeks: 0.978, 0.163-1.794).SGLT2 inhibitors reduced the risk of acute kidney injury (AKI) (OR 0.836; 95% CI 0.747-0.936; I<sup>2</sup> = 0%), mainly derived from empagliflozin (P = 0.001) and increased the incidence of volume-related adverse events (AEs) by 23%.However, no statically differences were observed in death due to kidney disease (P = 0.182) or events of eGFR < 15 mL/min/1.73 m<sup>2</sup> (P = 0.202).</p><p><strong>Conclusions: </strong>The results of our meta-analysis showed that after 64 weeks of treatment, SGLT2 inhibitors showed a significant benefit on eGFR rate with no further decline after 13 weeks and the improvement was slighter in lower eGFR values. Additionally, SGLT2 inhibitors reduce AKI when using empagliflozin, while there is an increased risk of volume-related AEs exclusively in stage 2 CKD. Trial registration CRD42023437061.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"5"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eram Albajri, Arwa S Almasaudi, Hala H Mosli, Noor A Hakim, Reem O Basaqr, Manal Naseeb
{"title":"Assessing the impact of magnesium-based nutritional education on lipid profiles in individuals with type 2 diabetes mellitus: a quasi-experimental study.","authors":"Eram Albajri, Arwa S Almasaudi, Hala H Mosli, Noor A Hakim, Reem O Basaqr, Manal Naseeb","doi":"10.1186/s13098-024-01566-8","DOIUrl":"10.1186/s13098-024-01566-8","url":null,"abstract":"<p><strong>Background: </strong>The potential therapeutic role of magnesium (Mg) in type 2 diabetes mellitus (T2DM) remains insufficiently studied despite its known involvement in critical processes like lipid metabolism and insulin sensitivity. This study examines the impact of Mg-focused nutritional education on lipid profile parameters, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in T2DM patients.</p><p><strong>Methods: </strong>Thirty participants with T2DM were recruited for this within-subject experimental study. Participants underwent a three-month dietary intervention focused on increasing the intake of Mg-rich foods through nutritional education. Anthropometric measurements and lipids were assessed at baseline and after the intervention period, with the primary outcome variables including changes in lipid parameters.</p><p><strong>Results: </strong>The findings showed a significant inverse association between dietary Mg intake and total cholesterol levels (r = - 0.36, p = 0.05). However, other parameters, TG, LDL-C, and HDL-C, were not found to be associated with Mg intake.</p><p><strong>Conclusion: </strong>The study demonstrated an inverse association between Mg intake and cholesterol level. Providing nutritional education and guidance on incorporating Mg-rich foods into the diet may be a crucial strategy for improving the health and well-being of T2DM patients in Saudi Arabia. The feasibility and practicality of focused nutritional education as an intervention make it a low-cost, scalable, and sustainable approach that can be readily implemented in clinical and community settings. Further studies are needed to explore the long-term impact of dietary Mg interventions on a larger sample with longer education periods.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"3"},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926909","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}
Vanessa Estato, Nathalie Obadia, Paulo Henrique Chateaubriand, Vivian Figueiredo, Marcela Curty, Mariana Costa Silva, Renata Gabriela Lustosa Ferreira, Juliane Santa-Ritta, Marcela Campos Baroni, Alessandra Aragão, João Oliveira Góes Neno, Clara Avelar Mendes Vasconcellos, Joana Costa D'Avila, Marcelo Gomes Granja, Hugo Caire de Castro Faria-Neto
{"title":"Semaglutide restores astrocyte-vascular interactions and blood-brain barrier integrity in a model of diet-induced metabolic syndrome.","authors":"Vanessa Estato, Nathalie Obadia, Paulo Henrique Chateaubriand, Vivian Figueiredo, Marcela Curty, Mariana Costa Silva, Renata Gabriela Lustosa Ferreira, Juliane Santa-Ritta, Marcela Campos Baroni, Alessandra Aragão, João Oliveira Góes Neno, Clara Avelar Mendes Vasconcellos, Joana Costa D'Avila, Marcelo Gomes Granja, Hugo Caire de Castro Faria-Neto","doi":"10.1186/s13098-024-01528-0","DOIUrl":"10.1186/s13098-024-01528-0","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic syndrome (MetS) is a metabolic disorder related to obesity and insulin resistance and is the primary determinant of the development of low-intensity chronic inflammation. This continuous inflammatory response culminates in neuroimmune-endocrine dysregulation responsible for the metabolic abnormalities and morbidities observed in individuals with MetS. Events such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in individuals with MetS may contribute to the activation of the innate immune response, which compromises cerebral microcirculation and the neurovascular unit, leading to the onset or progression of neurodegenerative diseases.</p><p><strong>Objective: </strong>This study aimed to evaluate the effects of chronic treatment with a GLP-1 receptor agonist (semaglutide) on cerebral microcirculation and neurovascular unit (NVU) integrity.</p><p><strong>Methods: </strong>C57BL/6 mice were fed a standard normolipidic diet or a high-fat diet (HFD) for 24 weeks and then treated for 4 weeks with semaglutide (HFD SEMA) or saline solution (HFD SAL). At the end of pharmacological treatment, biochemical analyses, immunohistochemistry analysis, and intravital microscopy of the brain microcirculation were carried out to quantify leukocyte-endothelium interactions and to assess structural capillary density, astrocyte coverage on cerebral vessels and microglial activation.</p><p><strong>Results: </strong>We observed that SEMA attenuates high-fat diet-induced metabolic alterations in mice fed with HFD for 24 weeks. SEMA also reversed cerebral microcirculation effects of HFD by reducing capillary rarefaction and the interaction of leukocytes in postcapillary brain venules. The HFD-SEMA group exhibited improved astrocyte coverage on vessels. However, SEMA did not reverse microglial activation.</p><p><strong>Conclusions: </strong>Semaglutide can reverse microvascular rarefaction in metabolic syndrome by restoring the integrity of the neurovascular unit. Adverse dietary stimuli can compromise microglial homeostasis that is not reversed by semaglutide.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"2"},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926930","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":"Relationship between BMI, indicators of lipid metabolism and diabetic neuropathy: a Mendelian randomization study.","authors":"Yuanyuan Jia, Guanying Liu, Xuesong Li, Lijun Duan, Lifeng Zhao","doi":"10.1186/s13098-024-01543-1","DOIUrl":"https://doi.org/10.1186/s13098-024-01543-1","url":null,"abstract":"<p><strong>Background: </strong>To identify the relationship between BMI or lipid metabolism and diabetic neuropathy using a Mendelian randomization (MR) study.</p><p><strong>Methods: </strong>Body constitution-related phenotypes, namely BMI (kg/m<sup>2</sup>), total cholesterol (TC), and triglyceride (TG), were investigated in this study. Despite the disparate origins of these data, all were accessible through the IEU OPEN GWAS database ( https://gwas.mrcieu.ac.uk/ ). Instrumental variables and F-statistics for each exposure-outcome pair were determined in weighted mode, weighted median, MR-Egger and Inverse-Variance Weighted (IVW) MR analyses. The p-value threshold was consistently set at 5.00E-08, following established methodology. The preliminary analysis utilized the IVW method to explore potential causal relationships between body constitution-related phenotypes and diabetic neuropathy. Inverse variance weighting, a technique amalgamating random variables, assigns weights inversely proportional to each variable's variance, commonly used for merging findings from independent studies. The weighted median method provides a causal estimate even when up to 50% of the instruments are invalid, enhancing robustness. The weighted mode method identifies the most common causal effect, reducing bias when some instruments exhibit horizontal pleiotropy. The Wald ratio method was utilized to calculate exposure-outcome effects, employing a range of methodologies to ensure result accuracy across different scenarios. This study addresses the critical gap in understanding the causal relationship between BMI, lipid metabolism, and diabetic neuropathy (DN). Employing a MR approach, it highlights BMI as a predictive factor for DN progression, providing insights into potential risk management strategies.</p><p><strong>Results: </strong>IVW analysis showed that BMI (P = 0.033, OR = 2.53, 95% CI 1.08-5.96) and triglycerides level (P = 0.593, OR = 1.11, 95% CI 0.77-1.60) were positively associated with the initiation of DN, indicating that the values of BMI and triglycerides are potentially the risk factors in DN development. Additionally, TC was negatively associated with the DN (P = 0.069, OR = 0.72, 95% CI = 0.50-1.03).The forest plot of advanced analysis between BMI and DN relationship indicated a positive correlation between increasing BMI and the risk of DN. In addition, it is evident that with the increase in BMI, the risk of diabetic polyneuropathy also rises. This research demonstrates a positive association between BMI and DN risk (P = 0.033, OR = 2.53, 95% CI = 1.08-5.96). However, no significant correlation was observed between triglycerides (P = 0.593) or total cholesterol (P = 0.069) and DN development, underscoring the complex interplay between lipid metabolism and DN.</p><p><strong>Conclusion: </strong>This research demonstrates a positive association between the risk of DN and BMI, while no significant correlation exists between TG or TC and the dev","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926929","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":"Effects of stress hyperglycemia ratio upon long-lasting prognosis in coronary artery disease patients with or lacking chronic renal impairment: findings from a Chinese multi-center observational study.","authors":"Jielan Wu, Jin Liu, Ziyao Yuan, Shangyi Tang, Weipeng Zhang, Yulong Xiang, Jinming Chen, Qiqiang Lin, Wei Guo, Yibo He, Haozhang Huang, Xiaozhao Lu, Jingru Deng, Huangtao Ruan, Rengui Jiang, Shiqun Chen, Yong Liu","doi":"10.1186/s13098-024-01521-7","DOIUrl":"10.1186/s13098-024-01521-7","url":null,"abstract":"<p><strong>Background: </strong>Lately, numerous researches have portrayed stress hyperglycemia ratio (SHR) is predominantly connected with short-term adverse prognosis among individuals who have acute coronary syndrome. Nevertheless, the relation of SHR with prolonged effects and the value of SHR in predicting in coronary artery disease (CAD) patients with or lacking chronic kidney disease (CKD) remain unclear. The present study was designed to elucidate the relation of SHR with prolonged prognosis and the value of SHR in predicting the long-term all-cause and cardiovascular death of CAD patients with CKD or non-CKD.</p><p><strong>Methods: </strong>We assessed 45,780 adults with CAD from a Chinese multi-center registry. SHR was computed via a formula [SHR = (admission glucose) (mmol/L) / (1.59 * HbA1c [%] - 2.59)]. Based on the presence or absence of CKD and SHR levels, patients were categorized into four groups. Long-term all-cause and cardiovascular mortality were the primary endpoints. The Kaplan-Meier method, restricted cubic spline (RCS), cox regression analysis, subgroups analysis, and sensitivity analysis were employed to estimate the connection between SHR and all-cause as well as cardiovascular mortality.</p><p><strong>Results: </strong>During a median follow-up of 5.2 years ( IQR 3.0-8.0), among 45,780 CAD patients (mean age [SD]: 62.8 ± 10.6 years; 23.9% female), the number of all-cause deaths was 7144(15.6%), and cardiovascular-related deaths was 3255 (7.1%). In cohorts with CKD, patients with high SHR had higher all-cause mortality (30.2% vs. 27.6%; adjusted hazard ratio HR 1.13, 95% CI 1.04-1.22; P = 0.003) and cardiovascular mortality (18.2% vs. 15.6%; HR adjusted 1.17, 95% CI 1.06-1.30; P = 0.002) compared to the individuals in low SHR. However, this was not the case in CAD cohorts without CKD [all-cause mortality (12.9% vs. 11.9%; HR adjusted 1.04, 95%CI 0.98-1.10, P = 0.206); cardiovascular mortality (5.1% vs. 4.4%; HR adjusted 1.09, 95%CI 0.99-1.20, P = 0.084)]. KM analysis revealed that high SHR is linked with all-cause mortality [CKD (log-rank P < 0.001); no-CKD (log-rank P = 0.024)] and cardiovascular mortality [CKD (log-rank P < 0.001); no-CKD (log-rank P = 0.01)] in CAD patients with or without CKD. RCS demonstrated that the relation between SHR and all-cause mortality was U-shaped after full modification, which was shown for CKD patients (P for non-linearity = 0.003) and also for patients without CKD (P for non-linearity = 0.001). Analogous effects were discovered for cardiovascular mortality, which was the case for CKD patients (P for non-linearity < 0.001) and also for patients without CKD (P for non-linearity = 0.001).</p><p><strong>Conclusions: </strong>Among patients with CAD, an elevated stress hyperglycemia ratio (SHR) is implicated in a heightened risk of long-term outcomes, particularly in those with CKD. This signifies that SHR might have a latent function in the cardiovascular risk categorization of the CAD po","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"316"},"PeriodicalIF":3.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11689691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909495","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}