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Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus.

ABSTRACT: Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients.

SUBMITTER: Garcia-Fontana B

PROVIDER: S-EPMC4463599 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus.

García-Fontana Beatriz B Morales-Santana Sonia S Longobardo Victoria V Reyes-García Rebeca R Rozas-Moreno Pedro P García-Salcedo José Antonio JA Muñoz-Torres Manuel M

International journal of molecular sciences 20150427 5

Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by ...[more]

PMID: 25923078

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Project description:Background: Glycosylated hemoglobin (HbA1c) variability is a risk factor for cardiovascular complications in patients with Type 2 diabetes mellitus (T2DM), but its relationship with the severity of coronary artery disease (CAD) is unclear. Methods: Patients with T2DM who underwent coronary angiography due to angina were enrolled. HbA1c variability was expressed as coefficient of variation (CV), standard deviation (SD), variability independent of mean (VIM), and time in range (TIR). The severity of CAD was expressed by the number of involved vessels and Gensini score. Multivariate regression models were constructed to test the relationship between HbA1c variability, number of involved vessels, and the Gensini score, followed by linear regression analysis. Results: A total of 147 patients were included. In multivariate analysis, VIM-HbA1c (OR = 2.604; IQR: 1.15, 5.90; r = 0.026) and HbA1cTIR (OR = 0.13; IQR: 0.04, 0.41; r < 0.001) were independent risk factors for the number of involved vessels. After adjustment, HbA1cTIR (OR = 0.01; IQR: 0.002, 0.04; r < 0.001), SD-HbA1c (OR = 4.12, IQR: 1.64, 10.35; r = 0.001), CV-HbA1c (OR = 1.41, IQR: 1.04, 1.92; r = 0.007), and VIM-HbA1c (OR = 3.26; IQR: 1.43, 7.47; r = 0.003) were independent risk factors for the Gensini score. In the linear analysis, the Gensini score was negatively correlated with HbA1cTIR (β = -0.629; r < 0.001) and positively correlated with SD-HbA1c (β = 0.271; r = 0.001) and CV-HbA1c (β = 0.176; r = 0.033). After subgroup analysis, HbA1cTIR was a risk factor for the number of involved vessels. The Gensini score was negatively correlated with HbA1cTIR and positively correlated with SD-HbA1c at subgroups of subjects with a mean HbA1c ≤ 7%. Conclusions: Our analysis indicates that HbA1c variability, especially HbA1cTIR, plays a role for the severity of CAD in patients with T2DM. HbA1c variability may provide additional information and require management even at the glycemic target. Translational Aspects: Studies have shown that HbA1c variability is related to cardiovascular complications. Further, we explore the correlation between HbA1c variability and the severity of CAD. HbA1c variability is a risk factor for coronary stenosis in T2DM. It may be a potential indicator reflecting glycemic control for the prevention and treatment of cardiovascular complications.

Project description:BackgroundDiabetes mellitus (DM) stands as the most prevalent endocrine abnormality affecting the physiological systems and organs and impairing the male reproductive functions. Type 2 Diabetes Mellitus (T2DM), accounting for about 90-95% of DM, is closely associated with male infertility. However, the magnitude of the causal relationships between T2DM and male infertility remains unclear. The current investigation was to explore the causal relationship between T2DM and male infertility utilizing the Mendelian Randomization (MR) analysis.MethodsA two-sample MR (2SMR) analysis was conducted to investigate the causal relationship between T2DM and male infertility in the European population from the genome-wide association study (GWAS) summary data that was publicly accessible. GWAS for T2DM and male infertility were extracted from the IEU Open GWAS Project database, with the resulting data encompassing 680 cases and 72,799 controls as the outcome data. Five MR methods were employed for the 2SMR analyses, namely the MR-Egger, weighted median estimation (WME), weighted mode (WM), inverse-variance weighted (IVW), and simple mode. The primary analytical technique utilized in this study was the IVW method, and a multivariate MR analysis was executed to examine the potential mediating influences of T2DM on male infertility.ResultsFollowing were the odds ratios (ORs) and associated 95% CIs derived from IVW (fixed effects), MR-Egger, WM, WME, and simple mode approaches: 0.824 (95% CI 0.703-0.966), 0.726 (95% CI 0.527-1.001), 0.827 (95% CI 0.596-1.150), 0.841 (95% CI 0.654-1.082), and 0.875 (95% CI 0.544-1.405), respectively. The outcomes of the heterogeneity tests were P=0.378 and P=0.384, respectively, implying no heterogeneity. Egger-intercept outcomes were P=0.374, highlighting the absence of pleiotropy. The stability of the results was affirmed through the leave-one-out analysis. Notably, all F-values surpassed 10, indicating the absence of weak bias attributed to instrument variables(IVs).ConclusionsThis research furnishes evidence supporting a causal association between T2DM and male infertility. These insights offer a foundation for future investigations aiming to establish the association between genetically predicted T2DM and male infertility. These outcomes suggest the significance of active monitoring and proactive measures for preventing infertility in male individuals with T2DM. Furthermore, careful consideration is required for individuals of reproductive age to prevent and treat T2DM.

Project description:8-Oxo-2'-deoxyguanosine (8-oxo-2'-dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8-oxo-2'-dG and major cardiovascular outcomes in diabetes mellitus is weak. A case-cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow-up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8-oxo-2'-dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1-SD increase in plasma 8-oxo-2'-dG was 1.10 (95% confidence interval, 1.01-1.20; P=0.03). This was driven by an independent association between plasma 8-oxo-2'-dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10-1.37 [P<0.001]). By contrast, no association was seen between 8-oxo-2'-dG and noncardiovascular disease death (of which cancer was the major single cause). 8-Oxo-2'-dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke. In adults with type 2 diabetes mellitus, increased levels of 8-oxo-2'-dG are independently associated with all-cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

Dataset Information

Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus.

Publications

Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus.

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