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Proteomic characteristics of circulating microparticles in patients with newly-diagnosed type 2 diabetes.

ABSTRACT: OBJECTIVE:This study aimed to evaluate the proteomic characteristics of plasma microparticles (MPs) from patients with newly diagnosed type 2 diabetes (T2DM). METHODS:The subjects comprised eight male T2DM patients recruited between December 2013 and March 2014, as well as eight age and sex-matched healthy controls enrolled during the same period. Plasma microparticles (MPs) were extracted from the blood of each subject, and subjected to proteomics analysis using label-free methods. Bioinformatic analyses were performed using specialized software. RESULTS:3,148 unique peptides and 496 proteins were identified, among these, 46 proteins were differentially expressed between the two groups. Among these 46 candidates, 20 proteins had higher expression in T2DM group compared with the control group, whereas 3 proteins displayed lower expression. There were 17 proteins only detected in T2DM group, and 6 proteins only detected in the control group. Gene ontology (GO) analysis revealed significant differences between the two groups in some functional nodes, including neutrophil accumulation, chemokine production, platelet activation, and blood coagulation. Pathway analysis showed that proteins involved in platelet activation, cell adhesion, focal adhesion, and extracellular matrix-receptor interaction were differentially expressed between the 2 groups. Network analysis indicated that ubiquitin was the protein with the highest degree of connectivity. CONCLUSIONS:Blood MPs from T2DM patients are enriched in proteins involved in platelet activation, cell adhesion, and inflammation. Therefore, MPs in T2DM patients might be associated with hypercoagulable state in diabetic patients and the development of diabetic complications.

SUBMITTER: Xu MD

PROVIDER: S-EPMC4759430 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Proteomic characteristics of circulating microparticles in patients with newly-diagnosed type 2 diabetes.

Xu Min-Dan MD Wu Xian-Zheng XZ Zhou Yun Y Xue Ying Y Zhang Ke-Qin KQ

American journal of translational research 20160115 1

<h4>Objective</h4>This study aimed to evaluate the proteomic characteristics of plasma microparticles (MPs) from patients with newly diagnosed type 2 diabetes (T2DM).<h4>Methods</h4>The subjects comprised eight male T2DM patients recruited between December 2013 and March 2014, as well as eight age and sex-matched healthy controls enrolled during the same period. Plasma microparticles (MPs) were extracted from the blood of each subject, and subjected to proteomics analysis using label-free method ...[more]

PMID: 27069554

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Project description:AimThere are increasing evidence demonstrating that neutrophil-mediated inflammation plays a role in the etiology of type 2 diabetes. However, the molecular mechanisms by which neutrophils contribute to type 2 diabetes remain largely unknown. The aim of the present work was to identify possible changes in circulating neutrophils to better elucidate neutrophil involvement in human type 2 diabetes.MethodsPatients newly diagnosed with type 2 diabetes (n = 5) and age- and sex-matched healthy controls (n = 5) were recruited. Neutrophils were purified from type 2 diabetes patients and controls, and RNA sequencing (RNA-seq) was used for comprehensive transcriptome analysis. Differentially expressed genes (DEGs) were screened, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. Real-time polymerase chain reaction (qPCR) was used for validation in external samples of type 2 diabetes patients (n = 8) and healthy controls (n = 8).ResultsGene expression analysis showed that, compared with neutrophils from healthy controls, there were 1990 upregulated DEGs and 1314 downregulated DEGs in neutrophils from type 2 diabetes patients. GO analysis demonstrated that the DEGs were mainly involved in myeloid leukocyte activation, T cell activation, adaptive immunity, and cytokine production. The top 20 enriched KEGG pathways included the cytokine-cytokine receptor interaction pathway, NF-κB signaling pathway, cell adhesion molecules, and chemokine signaling pathway. Furthermore, qPCR of genes related to neutrophil activation revealed that the expression of SELL, SELP, CXCR1, and S100A8 was significantly increased in neutrophils from type 2 diabetes patients compared with that in neutrophils from controls.ConclusionsOur study reveals an abnormal activation of circulating neutrophils at the transcriptome level in type 2 diabetes patients. These findings suggest a potential involvement of neutrophil dysfunction in the pathologic process of type 2 diabetes and provide insight into potential therapeutic targets for type 2 diabetes.

Project description:IntroductionWomen with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM.MethodsThis study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions.ResultsA total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year post-diagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects.ConclusionDifferences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment.

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Proteomic characteristics of circulating microparticles in patients with newly-diagnosed type 2 diabetes.

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Proteomic characteristics of circulating microparticles in patients with newly-diagnosed type 2 diabetes.

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