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      Influencing Factors of New-Onset Diabetes after a Renal Transplant and Their Effects on Complications and Survival Rate

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          Abstract

          Objective

          To discuss the onset of and relevant risk factors for new-onset diabetes after a transplant (NODAT) in patients who survive more than 1 year after undergoing a renal transplant and the influence of these risk factors on complications and long-term survival.

          Method

          A total of 428 patients who underwent a renal transplant between January 1993 and December 2008 and were not diabetic before surgery were studied. The prevalence rate of and relevant risk factors for postoperative NODAT were analyzed on the basis of fasting plasma glucose (FPG) levels, and differences in postoperative complications and survival rates between patients with and without NODAT were compared.

          Results

          The patients in this study were followed up for a mean of 5.65 ± 3.68 years. In total, 87 patients (20.3%) developed NODAT. Patients who converted from treatment with CSA to FK506 had increased prevalence rates of NODAT (P <0.05). Multi-factor analysis indicated that preoperative FPG level (odds ratio [OR]  =  1.48), age (OR  =  1.10), body mass index (OR  =  1.05), hepatitis C virus infection (OR  =  2.72), and cadaveric donor kidney (OR  =  1.18) were independent risk factors for NODAT (All P <0.05). Compared with the N-NODAT group, the NODAT group had higher prevalence rates (P < 0.05) of postoperative infection, hypertension, and dyslipidemia; in addition, the survival rate and survival time of the 2 groups did not significantly differ.

          Conclusion

          Among the patients who survived more than 1 year after a renal transplant, the prevalence rate of NODAT was 20.32%. Preoperative FPG level, age, body mass index, hepatitis C virus infection, and cadaveric donor kidney were independent risk factors for NODAT. Patients who converted from treatment with CSA to FK506 after a renal transplant had aggravated impairments in glycometabolism. Patients with NODAT were also more vulnerable to postoperative complications such as infection, hypertension, and hyperlipidemia.

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          Most cited references52

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          Diagnosis and classification of diabetes mellitus.

          (2007)
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            Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function.

            The growth and function of organs such as pancreatic islets adapt to meet physiological challenges and maintain metabolic balance, but the mechanisms controlling these facultative responses are unclear. Diabetes in patients treated with calcineurin inhibitors such as cyclosporin A indicates that calcineurin/nuclear factor of activated T-cells (NFAT) signalling might control adaptive islet responses, but the roles of this pathway in beta-cells in vivo are not understood. Here we show that mice with a beta-cell-specific deletion of the calcineurin phosphatase regulatory subunit, calcineurin b1 (Cnb1), develop age-dependent diabetes characterized by decreased beta-cell proliferation and mass, reduced pancreatic insulin content and hypoinsulinaemia. Moreover, beta-cells lacking Cnb1 have a reduced expression of established regulators of beta-cell proliferation. Conditional expression of active NFATc1 in Cnb1-deficient beta-cells rescues these defects and prevents diabetes. In normal adult beta-cells, conditional NFAT activation promotes the expression of cell-cycle regulators and increases beta-cell proliferation and mass, resulting in hyperinsulinaemia. Conditional NFAT activation also induces the expression of genes critical for beta-cell endocrine function, including all six genes mutated in hereditary forms of monogenic type 2 diabetes. Thus, calcineurin/NFAT signalling regulates multiple factors that control growth and hallmark beta-cell functions, revealing unique models for the pathogenesis and therapy of diabetes.
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              New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                9 June 2014
                : 9
                : 6
                : e99406
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
                [2 ]Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, P.R. China
                [3 ]Evidence Base Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
                [4 ]Department of Endocrinology and Metabolism, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (The People's Hospital of Fujian Province), Fuzhou, P.R. China
                [5 ]Department of Cadre's Ward, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian, P.R. China
                Children's Hospital Boston/Harvard Medical School, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MXY XG. Performed the experiments: CYL MLC MX. Analyzed the data: CYL GPX YZ SH. Contributed reagents/materials/analysis tools: MJX JG. Wrote the paper: CYL MXY XG TYZ.

                Article
                PONE-D-14-06186
                10.1371/journal.pone.0099406
                4050028
                24911157
                330953e6-02cc-4042-8d97-235ac8cc5d80
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 February 2014
                : 14 May 2014
                Page count
                Pages: 10
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Epidemiology
                Clinical Epidemiology
                Metabolic Disorders
                Diabetes Mellitus
                Type 1 Diabetes
                Type 2 Diabetes

                Uncategorized
                Uncategorized

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