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Purpose: This study was designed to analyze correlations between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and peripheral nerve conduction velocity (NCV) among type 2 diabetes mellitus (T2DM) patients. Patients and Methods: This was a single-center cross-sectional analysis of 324 T2DM patients. All patients were separated into a group with normal NCV (NCVN) and a group with abnormal NCV (NCVA). Patients were also classified into groups with low and high UHR values based on the median UHR in this study cohort. Neurophysiological data including motor and sensory conduction velocity (MCV and SCV, respectively) were measured for all patients. Results: Relative to patients with low UHR values, those in the high UHR group presented with greater NCVA prevalence (P = 0.002). UHR remained negatively correlated with bilateral superficial peroneal nerve SCV, bilateral common peroneal nerve MCV, bilateral ulnar nerve SCV, and bilateral right median nerve MCV even after adjustment for confounding factors. UHR was identified as an NCVA-related risk factor, with a 1.370-fold increase in NCVA prevalence for every unit rise in UHR (P < 0.001). Conclusion: These results identify UHR as a risk factor associated with NCVA that was independently negatively associated with NCV among T2DM patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN).Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV).Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94± 1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P< 0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c.Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients. [ABSTRACT FROM AUTHOR]

Objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM).Patients and Methods: This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups.Results: NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P< 0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P< 0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference.Conclusion: For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM. [ABSTRACT FROM AUTHOR]

Purpose: Among chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) is one of the commonest. Although empagliflozin has several therapeutic uses in treating cardiovascular and renal disorders, its impacts and mechanisms on NAFLD are poorly understood. This research aimed to examine the metabolic regulatory mechanism through which empagliflozin protects against NAFLD.Methods: Equal grouping of twenty-seven male C57BL/6J mice into those fed a normal diet (NCD), those fed a high-fat diet (HFD), and those fed an HFD with empagliflozin (Empa) was approached. HE, oil red O staining, and Masson staining were utilized for evaluating the pathological damage to the liver and the mice's liver and body weights. Lipids, blood glucose, and inflammation index were compared across the three groups. Liquid chromatography/mass spectrometry (LC-MS) has been employed for identifying liver metabolomics.Results: The findings suggested that empagliflozin mitigated the inflammatory and oxidative stress response associated with the buildup of lipids caused by HFD. Differentially expressed metabolites (DEMs) were identified by metabonomics analysis as present in both the HFD/NCD and Empa/HFD groups. These DEMs were primarily found in lipids and organic acids like lysophosphatidylcholine (lysoPC), lecithin (PC), triglyceride (TG), palmitic acid, and L-isoleucine. Among the enriched pathways that were shown to be important were those involved in the metabolism of histidine, arachidonic acid, the control of lipolysis in adipocytes, and insulin resistance. There was a strong correlation between inflammation and oxidative stress in most of the metabolites. The inflammation and oxidative stress unbalance were ameliorated by empagliflozin.Conclusion: NAFLD mice model showed considerable improvement in metabolic abnormalities and liver protection after treatment with empagliflozin. The process may include the overexpression of L-isoleucine and the downregulation of lysoPC, PC, TG, and palmitic acid to reduce liver harm caused by lipotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms. Methods: In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins. Results: We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues. Conclusion: The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role. [ABSTRACT FROM AUTHOR]

Purpose: To study the correlation between estimated glucose disposition rate (eGDR) and coagulation parameters in type 2 diabetes patients (T2DM). Materials and Methods: A total of 948 patients suffering from T2DM were enrolled for this research. Various blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were assessed. Body mass index (BMI), hypertension, and the levels of glycated hemoglobin (HbA1c) were used to calculate the patients' eGDRs. All patients were sorted into two groups: those with high eGDRs (eGDR≥ 7.5) and those with low eGDRs (eGDR< 7.5). The patients were then separated into groups of men and women. The connection between eGDR and coagulation indexes was examined using Spearman correlation, Pearson correlation, and multiple linear regression analysis. Results: In comparison to the high-eGDR group, reduced PT and APTT levels with increased FIB levels were observed in the low-eGDR group (P =0.006, P < 0.001, and P = 0.035, respectively). The eGDR showed a positive relation with APTT (r = 0.142, P < 0.001), a negative relation with FIB (r = − 0.082, P = 0.012), and no correlation with PT (r =0.064, P =0.050) in the all patients. As well as, the eGDR demonstrated a positive relation with APTT (r = 0.173, P < 0.001), a negative relation with FIB (r = − 0.093, P = 0.03), and no relation with PT (r = 0.045, P = 0.300) in the male subgroups. Additionally, this correlation persisted following the adjustment of other factors in multilinear regression analysis. However, the female subgroup demonstrated no correlation among eGDR and PT, APTT or FIB (r = 0.086, P = 0.083, r = 0.097, P = 0.05;r = − 0.058, P = 0.240, respectively). Conclusion: Our study is the first to prove that eGDR demonstrates a correlation with coagulation indexes in T2DM patients. And, this correlation is gender-specific. [ABSTRACT FROM AUTHOR]

Background. This study is aimed at exploring the key genes and the possible mechanism of heart damage caused by obesity. Methods. We analyzed the GSE98226 dataset. Firstly, differentially expressed genes (DEGs) were identified in heart tissues of obese and normal mice. Then, we analyzed DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Thirdly, we constructed a protein-protein interaction (PPI) network and key modules and searched hub genes. Finally, we observed the pathological changes associated with obesity through histopathology. Results. A total of 763 DEGs were discovered, including 629 upregulated and 134 downregulated genes. GO enrichment analysis showed that these DEGs were mainly related to the regulation of transcription, DNA-templated, nucleic acid binding, and metal ion binding. KEGG pathway analysis revealed that the DEGs were enriched in long-term depression, gap junction, and sphingolipid signaling pathways. Finally, we identified UTP14A, DKC1, DDX10, PinX1, and ESF1 as the hub genes. Histopathologic analysis showed that obesity increased the number of collagen fibers and decreased the number of microvessels and proliferation of the endothelium and increased endothelial cell damage which further leads to dysfunction of cardiac microcirculation. Conclusion. UTP14A, DKC1, DDX10, PinX1, and ESF1 have been identified as hub genes in obesity-induced pathological changes in the heart and may be involved in obesity-induced cardiac injury by affecting cardiac microcirculatory function. [ABSTRACT FROM AUTHOR]

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect. • Obesity can significantly increase cardiac collagen content and ventricular wall thickness. • Semaglutide affects the expression of several genes in non-cardiomyocytes of obese mice. • Obesity is involved in cardiac fibrosis by affecting the expression of Serpinh1 and Pcolce in cardiac fibroblasts. • Semaglutide alleviates cardiac fibrosis by inhibiting the expression of fibroblasts Serpinh1 and Pcolce. [ABSTRACT FROM AUTHOR]

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease. • A metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. • For the first time, metabolites, such as Adenosine, Uric acid, and Biliverdin were identified. • The molecular pathways were related to Phospholipids, Biliverdin and Purine metabolism. • Empagliflozin improved the oxidative stress and inflammation imbalance. • New insights into the renoprotective mechanisms of empagliflozin in targets for therapy. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for cardiovascular disease, leading to ventricular dysfunction and cardiac fibrosis, in which non-cardiomyocytes (nonCMs) play an important role. Early detection and treatment of heart illness may help to limit its progression. We screened for key markers of obesity-induced cardiac fibrosis using single-cell transcriptomics techniques. To begin, an obese mouse model was constructed using a high-fat diet. From a pathogenic perspective, pathological alterations in the obesity-induced heart were found. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. Then, to look for hub genes, key modules of DEGs were built. Finally, the cellular location of the hub genes was investigated. In mice, a high-fat diet raised body weight, messed up myocardial shape, and increased cardiac collagen content. NonCMs transcriptome data revealed 15 different cell types, including fibroblasts, immunological cells, and endothelial cells. There were a total of 33 DEGs found, with 22 up-regulated genes and 11 down-regulated genes. DEGs have a high connection with collagen and extracellular matrix (ECM), according to functional enrichment analysis. Col1a1 and Col1a2 scored well in module analysis and hub gene screening, and were chosen as hub genes. Col1a1 and Col1a2 were shown to be mostly expressed by fibroblasts after localization study. As a result, we believe Col1a1 and Col1a2 may be important markers of obesity-induced cardiac fibrosis, in which fibroblasts play a critical role. • Obesity can significantly increase cardiac collagen content and damage myocardial structure. • Obesity affects the expression of multiple genes in non-cardiomyocytes. • Obesity is involved in cardiac fibrosis by affecting the expression of Col1a1 and Col1a2 in cardiac fibroblasts. [ABSTRACT FROM AUTHOR]