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      Differential association of plasma monocyte chemoattractant protein-1 with systemic inflammatory and airway remodeling biomarkers in type-2 diabetic patients with and without asthma

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          Abstract

          Background

          Chronic inflammation is a hallmark of type-2 diabetes (T2D) and asthma. Monocyte chemoattractant protein (MCP)-1 or CCL-2 is a key regulator of monocytic infiltration into the sites of inflammation. The changes in systemic MCP-1 levels and its relationship with other inflammatory/immune markers in T2D patients with asthma remain unclear and have been addressed in this study.

          Methods

          Plasma samples from 10 asthmatic T2D patients (Group I: BMI = 37.82 ± 9.75 kg/m 2), 13 non-asthmatic T2D patients (Group II: BMI = 32.68 ± 4.63 kg/m 2), 23 asthma patients without T2D (Group III: BMI = 30.14 ± 6.74 kg/m 2), and 25 non-asthmatic non-diabetic controls (Group IV: BMI = 27.99 ± 5.86 kg/m 2) were used to measure levels of MCP-1 and multiple cytokine/chemokine biomarkers with bead-based multiplex assays using Luminex technology. IgE/ECP were measured using commercial ELISA kits. Data (mean ± SEM) were compared using unpaired Student’s t-test and linear dependence between two variables was assessed by Pearson’s correlation coefficient (r) and P ≤ 0.05 was considered as significant.

          Results

          Plasma MCP-1 levels were significantly higher in Group I (337.95 ± 46.40 pg/mL) as compared with Group II (216.69 ± 17.30 pg/mL), Group III (251.76 ± 19.80 pg/mL), and Group IV (223.52 ± 133.36 pg/mL). MCP-1 showed differential association with tested biomarkers by correlating positively with: (i) IFN-α2, IL-10, fractalkine, and VEGF in T2D patients with asthma; (ii) IL-6 and GRO-α in T2D patients without asthma; (iii) MDC, IP-10, GM-CSF, FGF-2, and PDGF-AA/BB in patients with asthma only; and (iv) FPG and TG in non-asthmatic non-diabetic controls. MCP-1 associated with IL-1RA only in subjects with asthma.

          Conclusion

          The systemic MCP-1 levels were significantly elevated in T2D patients with asthma as compared with those without asthma and/or diabetes while these changes correlated differentially with important biomarkers of inflammation and airway remodeling.

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          Most cited references 23

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          The cytokine network in asthma and chronic obstructive pulmonary disease.

           Peter Barnes (2008)
          Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases.
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            Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies.

            Although obesity has been implicated as an asthma risk factor, there is heterogeneity in the published literature regarding its role in asthma incidence, particularly in men. To quantify the relationship between categories of body mass index (BMI) and incident asthma in adults and to evaluate the impact of sex on this relationship. Online bibliographic databases were searched for prospective studies evaluating BMI and incident asthma in adults. Independent observers extracted data regarding annualized asthma incidence from studies meeting predetermined criteria, within defined categories of normal weight (BMI or= 30). Data were analyzed by inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI categories and within sex was performed. Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal weight, overweight and obesity (BMI >or= 25) conferred increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95% confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on asthma incidence was observed; the OR for incident asthma for normal-weight versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the trend). A similar increase in the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68; 95% CI, 1.45-1.94; p=0.232 for the comparison). Overweight and obesity are associated with a dose-dependent increase in the odds of incident asthma in men and women, suggesting asthma incidence could be reduced by interventions targeting overweight and obesity.
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              Targeting inflammation in the treatment of type 2 diabetes: time to start.

              The role of inflammation in the pathogenesis of type 2 diabetes and associated complications is now well established. Several conditions that are driven by inflammatory processes are also associated with diabetes, including rheumatoid arthritis, gout, psoriasis and Crohn's disease, and various anti-inflammatory drugs have been approved or are in late stages of development for the treatment of these conditions. This review discusses the rationale for the use of some of these anti-inflammatory treatments in patients with diabetes and what we could expect from their use. Future immunomodulatory treatments may not target a specific disease, but could instead act on a dysfunctional pathway that causes several conditions associated with the metabolic syndrome.
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                Author and article information

                Contributors
                sardar.sindhu@dasmaninstitute.org
                merin.koshy@dasmaninstitute.org
                areej.AbuAlRoub@dasmaninstitute.org
                nadeem.akhter@dasmaninstitute.org
                saad.alzanki@dasmaninstitute.org
                shamsha.ali@dasmaninstitute.org
                sriraman.devarajan@dasmaninstitute.org
                +965 2224 2999 , rasheed.ahmad@dasmaninstitute.org
                Journal
                J Diabetes Metab Disord
                J Diabetes Metab Disord
                Journal of Diabetes and Metabolic Disorders
                BioMed Central (London )
                2251-6581
                29 September 2016
                29 September 2016
                2015
                : 15
                Affiliations
                [1 ]Immunology & Innovative Cell Therapy Unit, P.O. Box 1180, Dasman, 15462 Kuwait
                [2 ]Tissue Bank Facility, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462 Kuwait
                Article
                264
                10.1186/s40200-016-0264-4
                5043607
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003286, Kuwait Foundation for the Advancement of Sciences;
                Award ID: RA-2011-015
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

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