Diabetes & vascular disease research最新文献

BackgroundTo evaluate the diagnostic value of lncRNA SNHG14 and miR-493-5p in gestational diabetes mellitus (GDM).MethodsThis study consisted of 128 GDM patients and 125 healthy controls. Dual luciferase reporter assay detected binding of lncRNA SNHG14 and miR-493-5p. ROC was applied to evaluate the diagnostic value of lncRNA SNHG14 and miR-493-5p for GDM. Independent factors affecting GDM were evaluated using logistic regression analysis. The role of lncRNA SNHG14, miR-493-5p in pregnancy outcome in GDM patients was assessed by chi-square tests.ResultsLncRNA SNHG14 has a target-binding relationship with miR-493-5p. LncRNA SNHG14 was significantly higher in GDM patients, while miR-493-5p was significantly lower; both were independent risk factors for GDM development. Blood glucose indices (fasting, 1 h and 2 h postprandial) were positively correlated with lncRNA SNHG14 and negatively correlated with miR-493-5p in GDM patients. LncRNA SNHG14 in combination with miR-493-5p increased the diagnostic efficiency for GDM. LncRNA SNHG14 was significantly associated with neonatal weight and neonatal jaundice. MiR-493-5p was significantly associated with neonatal jaundice.ConclusionLncRNA SNHG14 in combination with miR-493-5p may be an early diagnostic marker of GDM. LncRNA SNHG14 and miR-493-5p are associated with adverse pregnancy outcomes (macrosomia, neonatal jaundice) in patients with GDM.

ObjectivePatients with diabetes are 3-5 times higher at risk for cardiovascular diseases and myocardial infarction (MI). There is a need to find miRNAs and other target genes to reduce mortality rates. The current study aims to find potential miRNAs and target genes among MI patients, MI patients with pre-diabetes (metformin non-users), and MI patients with diabetes (metformin users).MethodThe candidate miRNAs were identified by microarray profiling, and their differential expression was evaluated through real-time polymerase chain reaction (RT-PCR) in control and patient groups. The potential targets for miR-1 and miR-133a were retrieved from the TargetScan, miRWalk, and miRDB databases. The sensitivity and specificity of miRNAs were assessed using receiver operating characteristic (ROC) curve analyses.ResultsMicroarray profiling identified 16 miRNAs with significantly altered expression in all MI patient groups compared with healthy controls. According to this data, two miR-1 and miR-133a (with a high ratio) were selected for further verification. All patient groups exhibited a significant increase in the expression levels of miR-1 and miR-133a. Also, miR-1 and miR-133a levels were lower in metformin-user patients than in non-user patients (p < 0.05). Moreover, interleukins, growth factors, and other related genes were identified as potential targets for miR-1 and miR-133a. The ROC area under the curve (AUC) was 0.973 (95% CI: 0.718-0.884) for circulating miR-1, and 0.969 (95% CI: 0.723-0.876) for miR-133a in patients with diabetes (p < 0.001).ConclusionPrediction of miRNA profiles and network of target genes are valuable in the early diagnosis of MI in individuals without and with diabetes. Metformin treatment is associated with lower expression of MI-related miRNAs, suggesting a potential mechanism for cardiac protection by this agent.

Introduction & ObjectiveLatent autoimmune diabetes mellitus (LADA), a heterogeneous disease, is much more common in society than thought. Although it has been claimed that LADA is similar to type 2 diabetes mellitus (T2DM) from a cardiovascular perspective, there is no clear consensus. In this context, the objective of this study is to assess subclinical dysfunction in the left and right ventricles in patients with LADA using novel tissue Doppler imaging (TDI) parameters.Materials &MethodsThe sample of this observational case-control study consisted of 57 consecutive patients aged between 30 and 70 years who applied to the endocrinology and metabolism outpatient clinics, were diagnosed with LADA, and were referred to the cardiology clinic for echocardiographic (ECHO) evaluation. The control group consisted of 60 healthy volunteers. Participants' demographic and clinical characteristics and laboratory findings were recorded. All participants underwent ECHO using conventional ECHO and TDI. Subclinical left ventricular dysfunction was assessed using the myocardial performance index (MPI) and isovolumic myocardial acceleration (IVA).ResultsThere were no significant differences between the patient and control groups in terms of conventional ECHO parameters. The left ventricular (LV) MPI was significantly higher in the patient group than in the control group (0.54 ± 0.11 vs 0.47 ± 0.07, p = 0.008). There was no significant difference between the groups in right ventricular (RV) MPI (0.49 ± 0.10 vs 0.46 ± 0.70, p = 0.217). IVA was decreased in both ventricles (IVA mitral: 3.03 ± 1.44 vs 3.78 ± 1.66, p = 0.008 and IVA tricuspid: 2.67 ± 0.88 vs 3.42 ± 0.97, p = 0.034). Both LV IVA and RV IVA were found to be significantly correlated with glutamic acid decarboxylase antibodies' (GADA) levels in the negative direction (R = -0.290, p = 0.005 and R = -0.340, p = 0.001).ConclusionsIt was observed that LADA negatively affected the systolic and diastolic functions of both ventricles, with its effect being more pronounced in the left ventricle. Glycemic control and autoantibody titers were found to be correlated with TDI parameters, emphasizing their relevance in assessing cardiac dysfunction.

ObjectiveImpairment of pancreatic β cells is a pathophysiological feature of type 2 diabetes mellitus (T2DM). However, whether abnormally dysregulated miR-454-3p in T2DM is related to the dysfunction of pancreatic β cell remains to be further investigated.MethodsFirst, T2DM patients and healthy subjects were recruited to measure miR-454-3p. Subsequently, pancreatic β cells were cultured with high glucose. The role of miR-454-3p in insulin synthesis, secretion, cell proliferation, and apoptosis were investigated by RT-qPCR, Glucose-stimulated insulin secretion determination, cell counting kit-8, and flow cytometry assays. The target mRNA of miR-454-3p was predicted using bioinformatics software. Then, the targeted binding relationships between the above two factors were verified through RNA Immunoprecipitation and Dual-Luciferase Reporter assays.ResultsThe expression of miR-454-3p was increased in T2DM patients and pancreatic β cells cultured with high glucose. Moreover, miR-454-3p was positively correlated with FPG and HbA1c levels in patients. In cell experiments, miR-454-3p inhibitors significantly improved the function of pancreatic β cells, including increased insulin synthesis and secretion, and promoted proliferation. Moreover, silencing Yy1 reversed the protective effect of miR-454-3p inhibitors on pancreatic β cells.ConclusionmiR-454-3p, which is dysregulated in T2DM, promotes the damage of pancreatic β cells by regulating Yy1, thus aggravating T2DM.

Background: Diabetic retinopathy (DR) is a microangiopathy resulting from diabetes mellitus. Studies on vitreous samples have shed insights into the etiology of DR and highlighted the role of molecular targets in DR treatment. The present study probed into the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in DR by examining its influence on inflammation, angiogenesis, matrix metalloproteinases (MMPs), and blood-retina barrier injury.Methods: After the induction of diabetes in rats through streptozotocin injection, SP-8356 (an inhibitor for EMMPRIN) was administered to rats for silencing EMMPRIN in vivo. Serum and vitreous EMMPRIN levels were assessed by ELISA and western blotting. The concentration and mRNA expression of proinflammatory cytokines in rat vitreous samples were quantified through ELISA or RT-qPCR. Western blotting or RT-qPCR was performed to measure protein or mRNA levels of MMPs, tight junction factors, and angiogenic factors.Results: High EMMPRIN levels were found in both serum and vitreous samples of DR rats. Inhibition of EMMPRIN using SP-8356 ameliorated DR-induced high levels of inflammatory cytokines, MMPs, and angiogenic factors and rescued DR-induced low expression levels of tight junction factors in rat vitreous samples.Conclusions: EMMPRIN accelerates inflammation, angiogenesis and blood-retina barrier injury in DR by regulating MMPs.

Objectives: This study aims to assess the association between the estimated glucose disposal rate (eGDR) and the risk of diabetic microvascular complications in patients with T1DM.Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted up to August 2024, including studies that examined the relationship between eGDR and diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN) in patients with T1DM. A meta-analysis was performed to compare the eGDR values in patients with and without microvascular complications and assess the risk of these complications.Results: 22 studies were included. Lower eGDR values were significantly associated with a higher risk of microvascular complications. Specifically, a one-unit increase in eGDR was associated with a 18% reduction in the risk of DKD (ES: 0.82, 95% CI: 0.74-0.92), a 21% reduction in the risk of DR (OR: 0.79, 95% CI: 0.73-0.85). Patients with DKD, DR, and DN had eGDR values significantly lower by 1.29, 0.75, and 0.64 units, respectively, compared to those without complications.Conclusion: This meta-analysis highlights the potential role of eGDR as a non-invasive marker for the early detection of microvascular complications, highlighting the importance of regular eGDR monitoring to facilitate timely interventions.

Background/Objective: Diabetes mellitus (DM) remains a major global health challenge due to its chronic nature and associated complications. Traditional diagnostic approaches, though effective, often lack the sensitivity required for early-stage detection. Recent advancements in molecular biology have identified RNA molecules, particularly non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as promising biomarkers for diabetes. This review aims to explore the role of RNA-based biomarkers in the diagnosis, prognosis, and management of diabetes, highlighting their potential to revolutionize diabetes care.Method: A comprehensive literature review was conducted using electronic databases including PubMed, Scopus, and Web of Science. Articles published up to 2024 were screened and analyzed to extract relevant findings related to RNA-based diagnostics in diabetes. Emphasis was placed on studies demonstrating clinical utility, mechanistic insights, and translational potential of RNA molecules.Results: Numerous RNA species, particularly miRNAs such as miR-375, miR-29, and lncRNAs like H19 and MEG3, exhibit altered expression patterns in diabetic patients. These molecules are involved in key regulatory pathways of glucose metabolism, insulin resistance, and β-cell function. Circulating RNAs are detectable in various biofluids, enabling non-invasive diagnostic approaches. Emerging technologies, including RNA sequencing and liquid biopsy platforms, have enhanced the sensitivity and specificity of RNA detection, fostering the development of novel diagnostic tools and personalized therapeutic strategies.Conclusion: RNA-based biomarkers hold significant promise in advancing early detection, risk stratification, and therapeutic monitoring in diabetes care. Despite current challenges such as standardization and clinical validation, the integration of RNA diagnostics into routine clinical practice could transform diabetes management, paving the way for precision medicine approaches. Further research and multi-center trials are essential to validate these biomarkers and facilitate their regulatory approval and clinical implementation.

IntroductionDiabetes related foot ulcers (DFUs) are common complications of type 2 diabetes mellitus (T2DM), affecting 15-25% of individuals living with diabetes and significantly contributing to healthcare costs ($9-13 billion annually in the U.S.). Without effective management, these wounds often lead to severe outcomes like amputations. This study aims to examine the association of semaglutide on DFU management.MethodsThis retrospective cohort study utilized TriNetX US Research Network data to assess the impact of semaglutide, a GLP-1 receptor agonist, on DFU outcomes between 2013 and 2023. The study compared outcomes between semaglutide users with DFU (Cohort A, N = 6329) and non-users with DFU (Cohort B, N = 118,821) across 64 healthcare organizations. We matched participants by age, gender, race, and ethnicity; however, we excluded patients with certain co-morbidities. Statistical analysis, such as chi-square analysis and risk ratio, using TriNetX software evaluated different complication outcomes.ResultsSemaglutide users with DFU demonstrated lower relative risks for complications compared to non-users. Within 1 year, semaglutide users were associated with lower relative risks for wound healing complications (0.19% vs 0.38%), chronic non-healing wounds (0.75% vs 1.23%), chronic pain (4.44% vs 8.06%), wound care (2.42% vs 4.86%), wound dehiscence (0.26% vs 0.56%), and amputation (2.34% vs 5.21%) (p < .05). Similar trends persisted over 5 years. While these findings highlight potential benefits of semaglutide with patients with DFU, causation cannot be inferred due to the study's observational design.ConclusionSemaglutide use was associated with favorable outcomes in patients with diabetes-related foot ulcers, including reductions in wound-related complications. While these findings suggest potential benefits of semaglutide as an adjunct in DFU management, further research is needed to confirm these associations and to better understand the mechanisms involved.

Background: Sleep insufficiency is known to negatively impact on glucose metabolism. Consequently, there is interest in determining the impact of improving sleep on glucose metabolism. We conducted a meta-analysis of studies that aimed at improving sleep using cognitive behavioural therapy for insomnia (CBT-I) and/or sleep hygiene or sleep extension on glucose metabolism.

Methods: Searches were performed on MEDLINE, EMBASE, CINAHL and Cochrane. We included studies featuring adults≥18years, a sleep intervention and glycaemic measurements. The pooled mean differences were calculated by the inverse variance method.

Results: 24 studies (15 CBT-I and/or sleep hygiene; 9 sleep extension) were included. Meta-analysis of 12 studies (n = 2,044) of CBT-I and/or sleep hygiene demonstrated a significant reduction in HbA1c of 0.27% (95% CI 0.07, 0.47, I² 74%, p = 0.008) compared to control. In T2DM (n = 1,911; 9 studies), HbA1c level decrease was 0.43% (0.19, 0.67, I² 59%, p = 0.0004). There were no significant changes in fasting blood glucose analyses nor in any sleep extension intervention. For quality assessment, only 9 studies had low concern.

Conclusions: Using CBT-I and/or sleep hygiene interventions led to significant reductions in HbA1c levels, which were clinically meaningful in T2DM. Addressing sleep insufficiency should be an integral part of diabetes care.

Registration: PROSPERO Identification number: CRD42022376606.

Aims: To evaluate the potential causal role of sleep traits (STs) on diabetic retinopathy (DR).

Methods: The cross-sectional study included 23,851 patients with type 2 diabetes from the UK Biobank and used multivariate logistic models to investigate the observational association between STs and DR. Genetic correlation analysis and two-sample Mendelian randomization (MR) were conducted using ST data from the UK Biobank and DR data from the FinnGen consortium to investigate the genetic and causal associations between STs and DR.

Results: Patients who experienced daytime sleepiness often/all of the time had a higher risk for DR (OR: 1.40; 95% CI, 1.09-1.79; p = .008) compared with those who sometimes/never/rarely experienced daytime sleepiness. Genetic correlations between several STs and DR were detected by cross-trait linkage disequilibrium score regression. MR suggested a causal effect of self-reported daytime sleepiness (OR: 4.08; 95% CI, 1.44-11.61; p = .008), and accelerator-derived sleep duration (OR: 0.73; 95% CI, 0.54-0.98; p = .036) and sleep efficiency (OR: 0.54; 95% CI, 0.36-0.80; p = .002) on DR.

Conclusions: STs may have a potential causal role for DR. Attention should be paid to the STs of patients for better prevention and treatment of DR.