Dataset Information

Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus.

ABSTRACT: C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 are two newly discovered adipokines regulating glucose and lipid metabolism. But their role in type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is still in infancy. The aim of this study was to investigate the associations of gene expression and serum levels of CTRP3 and CTRP13 with CAD, metabolic and inflammatory markers in patients with and without T2DM. Serum levels of CTRP3, CTRP13, adiponectin and inflammatory cytokines and their gene expression in peripheral blood mononuclear cells (PBMCs) were determined in 172 subjects categorized as group I (without T2DM and CAD), group II (with CAD but no T2DM), group III (with T2DM but no CAD) and group IV (with T2DM and CAD). Serum levels and gene expression of CTRP3, CTRP13 and adiponectin in the group I were higher compared to other groups. Inflammatory cytokines in the control group were lower than other groups too. CTRP3 serum levels have an independent association with BMI, smoking and CTRP3 gene expression; also CTRP13 serum levels has an independent association with BMI, HDL-C, insulin, HOMA-IR, HbA1c and TNF-?. Decreased serum levels of CTRP3 and CTRP13 were also associated with CAD. It appears that the decreased levels of CTRP3 and especially CTRP13 were associated with increased risk of T2DM and CAD. These findings suggest an emerging role of these adipokines in the pathogenesis of CAD, but further studies are necessary to establish this concept.

SUBMITTER: Fadaei R

PROVIDER: S-EPMC5199067 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus.

Fadaei Reza R Moradi Nariman N Baratchian Mehdi M Aghajani Hassan H Malek Mojtaba M Fazaeli Ali Akbar AA Fallah Soudabeh S

PloS one 20161229 12

C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 are two newly discovered adipokines regulating glucose and lipid metabolism. But their role in type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is still in infancy. The aim of this study was to investigate the associations of gene expression and serum levels of CTRP3 and CTRP13 with CAD, metabolic and inflammatory markers in patients with and without T2DM. Serum levels of CTRP3, CTRP13, adiponectin and inflammatory cytokines and their ...[more]

PMID: 28033351

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Project description:ObjectiveProgranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.Research design and methodsWe examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n?=?44) or without metabolic syndrome (n?=?83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT).ResultsCirculating progranulin levels are significantly related with inflammatory markers, hsCRP (r?=?0.30, P?=?0.001) and IL-6 (r?=?0.30, P?=?0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r?=?-0.21), diastolic blood pressure (r?=?-0.21), fasting glucose (r?=?-0.20), triglyceride (r?=?-0.34), total cholesterol (r?=?-0.25), eGFR (r?=?0.39) and adiponectin (r?=?0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P?=?0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r?=?0.227, P?=?0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R(2)?=?0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R(2)?=?0.365).ConclusionsSerum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome.Trial registrationClinicalTrials.gov NCT01668888.

Project description:Background:C1q TNF related protein 3 (CTRP3) is a relatively novel hormonal factor primarily derived from adipose tissue and has anti-diabetic properties. To determine if CTRP3 could play a role in early childhood development, the purpose of this study was to establish the presence of CTRP3 in breast milk (BM) and to determine whether CTRP3 levels were correlated with pregravid obesity status of the mother. Methods:Breast milk was collected from breast-feeding mothers who had a pregravid body mass index (BMI) classification of normal weight (BMI 18-25 kg/m2, n = 23) or obese (BMI > 30 kg/m2, n = 14). Immunoprecipitation followed by immunoblot analysis confirmed the presence of CTRP3 in BM. The concentration of CTRP3 in BM samples was determined by ELISA. Additional bioactive components were also measured by commercially available assays: ghrelin, insulin, leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?), and glucose. Bioactive components in normal weight and obese mothers were compared using unpaired t-test (parametric) and Mann-Whitney U-test (non-parametric), as appropriate. Results:The primary findings of this study are that the adipokine CTRP3 is present in BM and CTRP3 levels are increased with pregravid obesity. Additionally, this study independently confirmed previous work that BM from obese mothers has a higher concentration of insulin and leptin. Further, no differences were observed in BM between obese and normal weight mothers in ghrelin, adiponectin, IL-6, TNF-?, or glucose levels. Conclusion:This study identified a novel factor in BM, CTRP3, and showed that BM CTRP3 levels higher in obese mothers. Because of the purported insulin sensitizing effect of CTRP3, it is possible that the elevated levels of CTRP3 in the BM of obese mothers may offset negative effects of elevated leptin and insulin levels in the BM of obese mothers. Future studies will need to be conducted to determine the relevance of CTRP3 in BM and to examine the presence of other adipose tissue-derived hormonal factors.

Project description:BackgroundCoronary artery disease (CAD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The purpose of the present study was to discriminate the Indian CAD patients with or without T2DM by using multiple pathophysiological biomarkers.MethodsUsing sensitive multiplex protein assays, we assessed 46 protein markers including cytokines/chemokines, metabolic hormones, adipokines and apolipoproteins for evaluating different pathophysiological conditions of control, T2DM, CAD and T2DM with CAD patients (T2DM_CAD). Network analysis was performed to create protein-protein interaction networks by using significantly (p?<?0.05) altered protein markers in each disease using STRING 10.5 database. We used two supervised analysis methods i.e., between class analysis (BCA) and principal component analysis (PCA) to reveals distinct biomarkers profiles. Further, random forest classification (RF) was used to classify the diseases by the panel of markers.ResultsOur two supervised analysis methods BCA and PCA revealed a distinct biomarker profiles and high degree of variability in the marker profiles for T2DM_CAD and CAD. Thereafter, the present study identified multiple potential biomarkers to differentiate T2DM, CAD, and T2DM_CAD patients based on their relative abundance in serum. RF classified T2DM based on the abundance patterns of nine markers i.e., IL-1?, GM-CSF, glucagon, PAI-I, rantes, IP-10, resistin, GIP and Apo-B; CAD by 14 markers i.e., resistin, PDGF-BB, PAI-1, lipocalin-2, leptin, IL-13, eotaxin, GM-CSF, Apo-E, ghrelin, adipsin, GIP, Apo-CII and IP-10; and T2DM _CAD by 12 markers i.e., insulin, resistin, PAI-1, adiponectin, lipocalin-2, GM-CSF, adipsin, leptin, Apo-AII, rantes, IL-6 and ghrelin with respect to the control subjects. Using network analysis, we have identified several cellular network proteins like PTPN1, AKT1, INSR, LEPR, IRS1, IRS2, IL1R2, IL6R, PCSK9 and MYD88, which are responsible for regulating inflammation, insulin resistance, and atherosclerosis.ConclusionWe have identified three distinct sets of serum markers for diabetes, CAD and diabetes associated with CAD in Indian patients using nonparametric-based machine learning approach. These multiple marker classifiers may be useful for monitoring progression from a healthy person to T2DM and T2DM to T2DM_CAD. However, these findings need to be further confirmed in the future studies with large number of samples.

Dataset Information

Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus.

Publications

Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus.

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