Diabetology & Metabolic Syndrome最新文献

{"title":"Causal relationships between GLP1 receptor agonists, blood lipids, and heart failure: a drug-target mendelian randomization and mediation analysis.","authors":"Tianshi Mao, Jie Chen, Tong Su, Long Xie, Xinyan Qu, Ruli Feng, Yi Pan, Jie Wan, Xiaoyun Cui, Wenhao Jia, Qun Gao, Qian Lin","doi":"10.1186/s13098-024-01448-z","DOIUrl":"10.1186/s13098-024-01448-z","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF.</p><p><strong>Methods: </strong>The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator.</p><p><strong>Results: </strong>A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75-0.85, p < 0.0001) and decreased BMI (OR = 0.95, 95% CI = 0.93-0.96, p < 0.0001), ensuring the effectiveness of selected IVs. We found favorable evidence to support the protective effect of GLP1R agonism on HF (OR = 0.75, 95% CI = 0.71-0.79, p < 0.0001), but there was no obvious correlation with increased LVEF (OR = 1.01, 95% CI = 0.95-1.06, p = 0.8332). Among the six blood lipids, only low-density lipoprotein cholesterol (LDL-C) was both associated with GLP1R agonism and HF. The causal effect of GLP1R agonism on HF was partially mediated through LDL-C by 4.23% of the total effect (95% CI = 1.04-7.42%, p = 0.0093).</p><p><strong>Conclusions: </strong>This study supported the causal relationships of GLP1R agonists with a reduced risk of HF. LDL-C might be the mediator in this association, highlighting the cardiometabolic benefit of GLP1R agonists on HF.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"208"},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092519","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":"C-peptide: an essential ally in microvascular complications of type 2 diabetes mellitus and obesity.","authors":"Regina Esze, Sándor Barna, Péter Fülöp, Péter Kempler, Márton Mikó, Dénes Páll, György Paragh, Sándor Somodi, Miklós Emri, Zita Képes, Ildikó Garai, Miklós Káplár","doi":"10.1186/s13098-024-01454-1","DOIUrl":"10.1186/s13098-024-01454-1","url":null,"abstract":"<p><strong>Background: </strong>In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity.</p><p><strong>Methods: </strong>Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups.</p><p><strong>Results: </strong>Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05).</p><p><strong>Conclusions: </strong>Establishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"211"},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105164","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":"Effect of a carbohydrate-restricted diet on weight loss in overweight and obese pediatric population: a meta-analysis of randomized controlled trials.","authors":"Pejman Rohani, Zahra Rasoulizadeh, Sogand Tavakoli, Hosein Alimadadi, Koroush Vahidshahi, Somaye Fatahi, Mohammad Hassan Sohouli, Nathalia Sernizon Guimarães","doi":"10.1186/s13098-024-01458-x","DOIUrl":"10.1186/s13098-024-01458-x","url":null,"abstract":"<p><strong>Background: </strong>There are conflicting findings regarding the effect of low-carbohydrate diets on obesity-related factors. This study aimed to investigate the effect of a carbohydrate-restricted (CR) diet on changes in anthropometric indicators of adiposity and fat distribution in pediatrics populations.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Embase electronic databases using predefined keywords to identify all randomized controlled trials examining the effects of CR on obesity-related factors. The pooled weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using a random-effects model.</p><p><strong>Results: </strong>Findings from 11 studies demonstrated significant reductions in weight (WMD: -2.31 kg; 95% CI: -4.44, -0.18), BMI (WMD:-1.08 kg/m²; 95% CI: -1.91, -0.26), and fat mass (WMD: -1.43%; 95% CI: -2.43 to -0.43) as well as a significant increase in adiponectin levels (WMD: 0.74 ng/ml; 95% CI: 0.02, 1.47) in the CR diet group compared to the control group. However, no significant effect was observed on BMI z-score (WMD:-0.10; 95% CI: -0.21, 0.01), waist circumference (WMD:-3.03 cm; 95% CI: -6.57, 0.51) or leptin levels (WMD: -0.82 ng/ml; 95% CI: -2.26, 0.61). Stratified analysis rrevealed a greater effect of CR on weight and BMI reduction in interventions ≤ 12 weeks and in very low-carbohydrate diets.</p><p><strong>Conclusions: </strong>In conclusion, it appears that CR diet, along with other lifestyle factors, can lead to significant improvements in weight loss on pediatrics with obesity/overweight.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"210"},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105228","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":"Advancing healthcare with artificial intelligence: diagnostic accuracy of machine learning algorithm in diagnosis of diabetic retinopathy in the Brazilian population.","authors":"Mateus A Dos Reis, Cristiano A Künas, Thiago da Silva Araújo, Josiane Schneiders, Pietro B de Azevedo, Luis F Nakayama, Dimitris R V Rados, Roberto N Umpierre, Otávio Berwanger, Daniel Lavinsky, Fernando K Malerbi, Philippe O A Navaux, Beatriz D Schaan","doi":"10.1186/s13098-024-01447-0","DOIUrl":"10.1186/s13098-024-01447-0","url":null,"abstract":"<p><strong>Background: </strong>In healthcare systems in general, access to diabetic retinopathy (DR) screening is limited. Artificial intelligence has the potential to increase care delivery. Therefore, we trained and evaluated the diagnostic accuracy of a machine learning algorithm for automated detection of DR.</p><p><strong>Methods: </strong>We included color fundus photographs from individuals from 4 databases (primary and specialized care settings), excluding uninterpretable images. The datasets consist of images from Brazilian patients, which differs from previous work. This modification allows for a more tailored application of the model to Brazilian patients, ensuring that the nuances and characteristics of this specific population are adequately captured. The sample was fractionated in training (70%) and testing (30%) samples. A convolutional neural network was trained for image classification. The reference test was the combined decision from three ophthalmologists. The sensitivity, specificity, and area under the ROC curve of the algorithm for detecting referable DR (moderate non-proliferative DR; severe non-proliferative DR; proliferative DR and/or clinically significant macular edema) were estimated.</p><p><strong>Results: </strong>A total of 15,816 images (4590 patients) were included. The overall prevalence of any degree of DR was 26.5%. Compared with human evaluators (manual method of diagnosing DR performed by an ophthalmologist), the deep learning algorithm achieved an area under the ROC curve of 0.98 (95% CI 0.97-0.98), with a specificity of 94.6% (95% CI 93.8-95.3) and a sensitivity of 93.5% (95% CI 92.2-94.9) at the point of greatest efficiency to detect referable DR.</p><p><strong>Conclusions: </strong>A large database showed that this deep learning algorithm was accurate in detecting referable DR. This finding aids to universal healthcare systems like Brazil, optimizing screening processes and can serve as a tool for improving DR screening, making it more agile and expanding care access.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"209"},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105162","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":"Effect of SGLT-2 inhibitors on acute kidney injury in patients with heart failure: a systematic review and meta-analysis.","authors":"Xianghong Wang, Meihong He, Donghua Jin, Chuanchuan Sun, Hongyun Lu","doi":"10.1186/s13098-024-01446-1","DOIUrl":"10.1186/s13098-024-01446-1","url":null,"abstract":"<p><strong>Background: </strong>Sodium glucose cotransporter-2 (SGLT-2) inhibitors are known to reduce hospitalization and cardiovascular mortality in various heart failure (HF) populations, potentially through enhanced excretion of water and sodium. However, there are concerns regarding the risk of acute kidney injury (AKI) associated with their use. This meta-analysis aimed to unravel the effects of SGLT-2 inhibitors on risk of AKI in a variety of patients with HF.</p><p><strong>Methods: </strong>This study conducted a comprehensive literature search using PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov for studies published up to January 1, 2024. Data were analyzed using both random-effects or fixed-effects models to estimate the overall relative risk (RR) with a 95% confidence interval (CI).</p><p><strong>Results: </strong>Our analysis included 25,172 patients with HF from 16 randomized controlled trials. Treatment with SGLT-2 inhibitors led to a 28% reduction in the risk of AKI progression compared to placebo (RR 0.72, 95% CI 0.61-0.85, p<0.0001), without an increased risk of hypotension (RR 1.21, 95% CI 0.87-1.70, p = 0.26) and hypovolemia (RR 2.26, 95% CI: 0.70-7.33, p = 0.17). Notably, SGLT-2 inhibitors significantly decreased AKI in specific subgroups, including patients with HF with reduced ejection fraction (RR 0.59, 95% CI 0.43-0.80, p = 0.0007), those treated with empagliflozin (RR 0.70, 95% CI 0.57-0.88, p = 0.002) or dapagliflozin (RR 0.74, 95% CI 0.57-0.98, p = 0.04), in studies with a follow-up of at least 1 year (RR 0.67, 95% CI 0.55-0.82, p = 0.0001), and in patients aged 65 years or older (RR 0.72, 95% CI 0.61-0.85, p < 0.0001).</p><p><strong>Conclusion: </strong>Use of SGLT-2 inhibitors did not increase the incidence of AKI regardless of the ejection fraction environment (chronic and acute), type of SGLT-2 inhibitors, or patient age.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"207"},"PeriodicalIF":3.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079586","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":"Investigating CR1 as an indicated Gene for mild cognitive impairment in type 2 diabetes mellitus.","authors":"Xueling Zhou, Shaohua Wang, Dandan Yu, Tong Niu","doi":"10.1186/s13098-024-01449-y","DOIUrl":"10.1186/s13098-024-01449-y","url":null,"abstract":"<p><strong>Objective: </strong>Type 2 diabetes mellitus (T2DM) has beenis known as an important risk factor for cognitive impairment. Meanwhile, the liver plays a central role in the development of T2DM and insulin resistance. The present study attempted to identify and validate marker genes for mild cognitive impairment (MCI) in patients with T2DM.</p><p><strong>Methods: </strong>In this study, insulin resistance-related differentially expressed genes were identified from the liver tissues of individuals with T2DM and those with normal glucose tolerance using the Gene Expression Omnibus database and MCI-associated genes were identified using the GeneCards database. Next, enrichment analysis was performed with overlapping T2DM and MCI genes, followed by the identification of specific genes using the LASSO logistic regression and SVM-RFE algorithms. An important experiment involved the implementation of clinical and in vitro validation using real-time quantitative polymerase chain reaction (RT-qPCR). Finally, multiple linear regression, binary logistic regression, and receiver operating characteristic curve analyses were performed to investigate the relationship between the key gene and cognitive function in these patients.</p><p><strong>Result: </strong>The present study identified 40 overlapping genes between MCI and T2DM, with subsequent enrichment analysis revealing their significant association with the roles of neuronal and glial projections. The marker gene complement receptor 1(CR1) was identified for both diseases using two regression algorithms. Based on RT-qPCR validation in 65 T2DM patients with MCI (MCI group) and 65 T2DM patients without MCI (NC group), a significant upregulation of CR1 mRNA in peripheral blood mononuclear cells was observed in the MCI group (P < 0.001). Furthermore, the CR1 gene level was significantly negatively associated with MoCA and MMSE scores, which reflect the overall cognitive function, and positively correlated with TMTB scores, which indicate the executive function. Finally, elevated CR1 mRNA levels were identified as an independent risk factor for MCI (OR = 1.481, P < 0.001).</p><p><strong>Conclusion: </strong>These findings suggest that CR1 is an important predictor of MCI in patients with T2DM. Thus, CR1 has potential clinical significance, which may offer new ideas and directions for the management and treatment of T2DM. The identification and clinical validation of dysregulated marker genes in both T2DM and MCI can offer valuable insights into the intrinsic association between these two conditions. The current study insights may inspire the development of novel strategies for addressing the complicated issues related to cognitive impairment associated with diabetes.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"206"},"PeriodicalIF":3.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055210","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 variables of heart failure among patients in China: grey relational approach based multi-dimensional assessment study.","authors":"Xue Wang, Chao Deng, Xiantong Cao, Heng Gao","doi":"10.1186/s13098-024-01445-2","DOIUrl":"10.1186/s13098-024-01445-2","url":null,"abstract":"<p><strong>Background: </strong>Understanding the potential risk factors of heart diseases is key to effectively managing cardiac diseases. The present study quantifies the association of identified risk factors. In addition, the study has compared the association of mortality with hypertension, uncontrolled diabetes, and uncontrolled hyperlipidemia using Grey Relational Approach (GRA) for stroke, lung diseases, smoking, stress, obesity, and lack of exercise.</p><p><strong>Method: </strong>Data on risk factors of heart failure were collected from the Global Burden of Disease (GBD) study (2001-2017). From the GBD database, variables have selected the top leading risk factors responsible for mortality from cardiac diseases. Data on risk factors was analyzed using the GRA procedure (utilizing Grey [8.0] software). In the GRA method, the correlation was categorized into three components: GRA - Deng (assesses the effect of one variable specified by data on the other variables), GRA- absolute (assesses the association between variables measured), and GRA-SS (assessed the overall association between the variables measured). Stroke, lung diseases, smoking, stress, obesity, and lack of exercise were taken as dependent variables and their impact was assessed. Hypertension (high grade) uncontrolled diabetes, and uncontrolled hyperlipidemia were considered as independent variables. The relationship between dependent and independent variables was assessed.</p><p><strong>Results: </strong>Overall correlational analysis showed that type 2 diabetes (T2DM) is the risk factor that has a strong relationship with causing heart failure and thereby increases morbidity and mortality among Chinese patients. After T2DM, the second highest risk factor associated was severe dyslipidemia which is responsible for causing heart failure. High-grade hypertension is one-third most common risk factor in causing heart failure. GRA - Deng analysis showed that T2DM is the top risk factor associated with heart failure, followed by high-grade hypertension and severe dyslipidemia (uncontrolled). GRA-absolute analysis showed that severe dyslipidemia is the top risk factor associated with heart failure, followed by high-grade hypertension and T2DM (uncontrolled). GRA-SS analysis showed that high-grade hypertension is the top risk factor associated with heart failure, followed by severe dyslipidemia and T2DM (uncontrolled).</p><p><strong>Conclusions: </strong>The study reported that T2DM, severe dyslipidemia, and high-grade hypertension as strongly correlated with the development of heart failure after considering other several key risk factors (stroke, lung diseases, smoking, stress, obesity, and lack of exercise).</p><p><strong>Level of evidence: </strong>IV.</p><p><strong>Technical efficacy: </strong>Stage 5.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"205"},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035516","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":"Vildagliptin promotes diabetic foot ulcer healing through autophagy modulation.","authors":"Erik Biros, Venkat Vangaveti, Usman Malabu","doi":"10.1186/s13098-024-01444-3","DOIUrl":"10.1186/s13098-024-01444-3","url":null,"abstract":"<p><p>The study aimed to investigate the molecular mechanisms underlying the effects of Vildagliptin on the healing of diabetic foot ulcers (DFUs). The research compared patients who received 12 weeks of Vildagliptin treatment to those who did not. Various molecular markers associated with wound healing were measured. Wound fluid samples were collected from DFUs using a filter paper absorption technique, and total RNA was extracted for quantitative real-time PCR (qPCR). The results showed that the autophagy marker NUP62 was significantly downregulated in the Vildagliptin group at week 12 compared to baseline (median expression 0.57 vs. 1.28; P = 0.0234). No significant change was observed in the placebo group (median expression 1.61 vs. 1.48; P = 0.9102). Both groups showed substantial downregulation of RIPK3, a necroptosis marker, at week 12 compared to their respective baselines. In addition to its effects on blood sugar levels, Vildagliptin may promote DFU healing by reducing autophagy in patients with diabetes.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"204"},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035517","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":"Causal relationship between gut microbiota and diabetic complications: a two-sample Mendelian randomization study.","authors":"Jinya Liu, Yuanyuan Chen, Cheng Peng","doi":"10.1186/s13098-024-01424-7","DOIUrl":"10.1186/s13098-024-01424-7","url":null,"abstract":"<p><strong>Background: </strong>Imbalances in gut microbiota (GM) have been proposed as a potential contributing factor to diabetic complications; however, the causal relationship remains incompletely understood.</p><p><strong>Methods: </strong>Summary statistics were obtained from genome-wide association studies (GWAS) of 196 gut microbial taxa, including 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera. These data were then analyzed using mediation Mendelian randomization (MR) analyses to explore the potential mediating effect of diabetes complications risk factors on the relationship between gut microbiota and specific diabetic complications such as diabetic kidney disease (DKD), ketoacidosis, and diabetic retinopathy (DR).</p><p><strong>Results: </strong>In our Mendelian analysis, we observed negative associations between Bifidobacterial order and Actinomycete phylum with DKD in type 1 diabetes (T1D) as well as early DKD in T1D. Conversely, these taxa showed positive associations with ketoacidosis in type 2 diabetes (T2D). In reverse Mendelian analysis, we found that DR in both T1D and T2D as well as ketoacidosis in T2D affected the abundance of Eubacterium fissicaten genus and LachnospiraceaeUCG010 family within the gut microbiota.</p><p><strong>Conclusions: </strong>Our findings provide compelling evidence for causal relationships between specific GM taxa and various diabetes complications. These insights contribute valuable knowledge for developing treatments targeting diabetes-related complications.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"202"},"PeriodicalIF":3.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008467","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":"Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes.","authors":"Angelica Giuliani, Deborah Ramini, Matilde Sbriscia, Paolina Crocco, Luca Tiano, Maria Rita Rippo, Anna Rita Bonfigli, Giuseppina Rose, Maria De Luca, Fabiola Olivieri, Jacopo Sabbatinelli","doi":"10.1186/s13098-024-01431-8","DOIUrl":"10.1186/s13098-024-01431-8","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cellular senescence is emerging as a key mechanism of age-related vascular dysfunction. Disruption of the endothelium glycocalyx and shedding of the syndecan (SDC) ectodomains have been associated with several age-related diseases. Although SDC4 is highly expressed in endothelial cells, its levels and shedding in senescent endothelial cells and vascular endothelial dysfunction associated with aging are still unknown.</p><p><strong>Methods: </strong>To assess whether SDC4 expression was affected by inflammatory conditions, we evaluated its levels in young human umbilical vein endothelial cells (HUVECs) treated with TNF-α at a concentration of 50 ng/mL for 24 h and in cells undergoing replicative senescence. Plasma levels of SDC4 were evaluated in two previously recruited cohorts of (i) subjects with type 2 diabetes (T2D, n = 110) followed for a median of 16.8 years and age- and gender-matched healthy subjects (n = 100), and (ii) middle-aged subjects with mild-to-moderate dyslipidemia. Binomial logistic regression was used to assess whether SDC4 levels could be prognostic for major adverse cardiovascular events (MACE).</p><p><strong>Results: </strong>In the in vitro study, we showed that HUVECs, when exposed to TNF-α or undergoing replicative senescence, exhibited elevated expression levels of SDC4 and matrix metallopeptidase 9 (MMP-9), as well as increased shedding of SDC4 into the extracellular microenvironment, in comparison to actively proliferating young HUVECs. Analysis of human samples revealed that patients with T2D without complications exhibited higher SDC4 levels compared to healthy controls and those with T2D vascular complications. In particular, patients with a history of major adverse cardiovascular events (MACE) had lower SDC4 levels. The longitudinal evaluation revealed that higher SDC4 levels predict the onset of new MACE during a 16.8-year follow-up. In the second cohort, no significant association was observed between SDC4 and endothelial dysfunction, assessed by flow-mediated dilation (FMD) or nitric oxide metabolites. SDC4 levels correlated positively with C-reactive protein (CRP) in both cohorts and with PAI-1 in the cohort of patients with T2D.</p><p><strong>Conclusion: </strong>Overall, we conclude that the shedding of SDC4 from endothelial cells increases under acute (TNF-α treatment) and chronic (senescence) inflammatory conditions and that increased circulating SDC4 levels are associated with systemic inflammation in pathological aging.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"16 1","pages":"203"},"PeriodicalIF":3.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008416","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}