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      Association between MIC-1 and Type 2 Diabetes: A Combined Analysis

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          Abstract

          Background and Objectives

          Type 2 diabetes mellitus (T2DM) is an epidemic disease that endangers human health seriously. Recently, a large number of reports have revealed that macrophage-inhibiting cytokine-1 (MIC-1) is linked with T2DM, but the results were inconclusive. The aim of this study was to perform bioinformatics analysis of the association between MIC-1 and T2DM.

          Material and Methods

          Datasets and relevant literatures were searched in Gene Expression Omnibus (GEO), PubMed, Google Scholar, and Web of Science till September 20, 2019. Expression levels of MIC-1 were extracted, pooled, and compared between T2DM cases and controls.

          Results

          In summary, 11 GEO datasets and 3 articles with 421 T2DM cases and 711 controls were finally included. The expression level of MIC-1 was significantly higher in T2DM patients compared with controls, with a standard mean difference (SMD) of 0.54 and a 95% confidence interval (95% CI) of 0.24-0.83; in blood samples, the difference was still significant (SMD = 0.65; 95%CI = 0.24‐1.06). Meanwhile, the expression level of MIC-1 plays a significant role in differentiating T2DM cases from controls; the combined sensitivity, specificity, and odds ratio were 0.83 (95%CI = 0.72‐0.90), 0.59 (95%CI = 0.45‐0.72), and 1.64 (95%CI = 1.35‐1.99), respectively. The summary receiver operating characteristic (SROC) curve demonstrated that the area under the curve (AUC) was 0.81 (95%CI = 0.77‐0.84).

          Conclusion

          Our results suggested that the expression levels of MIC-1 were significantly higher in T2DM patients in multiple tissues including blood samples.

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          Most cited references30

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          IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

          To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040.
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            The Definition and Prevalence of Obesity and Metabolic Syndrome.

            Increase in prevalence of obesity has become a worldwide major health problem in adults, as well as among children and adolescents. Furthermore, total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis at adult ages. Centrally accumulation of body fat is associated with insulin resistance, whereas distribution of body fat in a peripheral pattern is metabolically less important. Obesity is associated with a large decrease in life expectancy. The effect of extreme obesity on mortality is greater among younger than older adults. In this respect, obesity is also associated with increased risk of several cancer types. However, up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy normal weight individuals, lower visceral fat content, and lower intima media thickness of the carotid artery than the majority of metabolically "unhealthy" obese patients.Abdominal obesity is the most frequently observed component of metabolic syndrome. The metabolic syndrome; clustering of abdominal obesity, dyslipidemia, hyperglycemia and hypertension, is a major public health challenge. The average prevalence of metabolic syndrome is 31%, and is associated with a two-fold increase in the risk of coronary heart disease, cerebrovascular disease, and a 1.5-fold increase in the risk of all-cause mortality.
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              MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily.

              Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor beta (TGF-beta) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interleukin 2, and macrophage colony-stimulating factor but not interferon gamma, or lipopolysaccharide (LPS). Its expression is also increased by TGF-beta. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of Mr 25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinflammatory cytokines and TGF-beta may serve to limit the later phases of macrophage activation.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2019
                16 November 2019
                : 2019
                : 7284691
                Affiliations
                1Department of Epidemiology and Biostatics, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, 199 Ren Ai Road, Suzhou, China
                2Community Health Service Center of Minglou, Subdistrict Jiangdong District, Ningbo, China
                3Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China
                Author notes

                Academic Editor: Ralf Lichtinghagen

                Author information
                https://orcid.org/0000-0002-9630-1793
                https://orcid.org/0000-0001-6682-0093
                https://orcid.org/0000-0001-6791-4833
                https://orcid.org/0000-0003-2671-3028
                https://orcid.org/0000-0002-8385-0961
                https://orcid.org/0000-0002-3315-8598
                https://orcid.org/0000-0002-0762-2094
                https://orcid.org/0000-0001-6457-6824
                https://orcid.org/0000-0001-9750-7999
                https://orcid.org/0000-0002-5265-3930
                https://orcid.org/0000-0002-5231-2562
                Article
                10.1155/2019/7284691
                6885201
                31827641
                38bd5a84-8627-4f5f-bc03-d8d4c41f8e3e
                Copyright © 2019 Jianan Lu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 April 2019
                : 23 September 2019
                : 3 October 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81602911
                Funded by: National Key R&D Program of China
                Award ID: 2017YFC1310701
                Award ID: 2017YFC1310700
                Categories
                Review Article

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