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      IL-34 causes inflammation and beta cell apoptosis and dysfunction in gestational diabetes mellitus

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          Abstract

          Objective

          Gestational diabetes mellitus (GDM) is characterized by glucose intolerance during gestation. It is associated with a series of maternal and foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and autoimmune diseases has been recently discovered. The aim of this study was to evaluate whether IL-34 participates in the pathogenesis of GDM.

          Method

          A total of 120 women were enrolled in this study, which included 60 GDM patients and age- and sex-matched healthy pregnant women. The expression of IL-34 in serum, cord blood and placental tissues was analysed by ELISA and Western blot assays. The association between IL-34 levels and clinical features was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rmIL-34) on apoptosis and pancreatic β cell function.

          Results

          We found that IL-34 expression is highly increased in serum, cord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentrations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic β cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inhibited pancreatic β cell function and cell viability, while CSF-1R inhibitor blocked this effect.

          Conclusion

          IL-34 plays a crucial role in the development of GDM by targeting CSF-1R, insulin production and β cell function.

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          Most cited references 31

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          Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

          The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
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            Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

            The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium–glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
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              Frequency of Gestational Diabetes Mellitus at Collaborating Centers Based on IADPSG Consensus Panel–Recommended Criteria

              OBJECTIVE To report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. RESEARCH DESIGN AND METHODS All participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively). RESULTS Overall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds. CONCLUSIONS Although the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                November 2019
                24 October 2019
                : 8
                : 11
                : 1503-1512
                Affiliations
                [1 ]Department of Radiology , The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China
                [2 ]Department of Human Anatomy , Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China
                [3 ]Department of Endocrinology and Metabolism , Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China
                [4 ]Department of Obstetrics , The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China
                [5 ]Department of Laboratory Medicine , The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China
                [6 ]Department of Gastroenterology , The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China
                Author notes
                Correspondence should be addressed to Y Wang: wangyiwei_symc@ 123456163.com
                Article
                EC-19-0436
                10.1530/EC-19-0436
                6865862
                31648183
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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