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      Serum levels of insulin-like growth factor 1 are negatively associated with log transformation of thyroid-stimulating hormone in Graves’ disease patients with hyperthyroidism or subjects with euthyroidism : A prospective observational study

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          Abstract

          Insulin-like growth factor 1 (IGF-1) has a molecular structure similar to that of insulin. As an essential mediator of growth hormone, IGF-1 plays a vital role in growth of children and anabolic effects of adults. We evaluated the serum levels of IGF-1 in patients with hyperthyroidism or euthyroidism.

          In this study, 30 patients each of Graves’ disease with hyperthyroidism (HY group) and euthyroid individuals (EU group) were recruited. The HY patients were treated with antithyroid regimens as clinically indicated. No medications were given to EU patients. The demographic characteristics and anthropometric and laboratory data of both groups at baseline and 6 months were compared. Associations between levels of IGF-1 and free thyroxine (fT4), thyroid-stimulating hormone (TSH), or log transformation of TSH (logTSH) were analyzed.

          At baseline, the HY patients had significantly higher serum IGF-1 levels than EU patients (median [Q1, Q3]: 305.4 [257.4, 368.1] vs. 236.7 [184.6, 318.8] ng/mL, P = .007). At 6 months, the HY patients still had higher serum levels of IGF-1 than EU patients (299.5 [249.9, 397.9] vs 222.1 [190.2, 305.4] ng/mL, P = .003). At baseline, the serum levels of IGF-1 in the HY and EU patients were positively associated with fT4 (β = 29.02, P = .002) and negatively associated with TSH (β = −31.46, P = .042) and logTSH (β = −29.04, P = .007). The associations between serum levels of IGF-1 with fT4 or TSH became insignificant at 6 months. However, the serum IGF-1 levels had persistent negative associations with logTSH at 6 months (β = −26.65, P = .021). The negative associations between IGF-1 and logTSH at baseline and 6 months remained significant even after adjustment with sex and age (β = −20.22, P = .023 and β = −20.51, P = .024, respectively).

          The HY patients had higher serum IGF-1 levels than EU patients. The serum IGF-1 concentrations were negatively associated with logTSH in patients with hyperthyroidism or euthyroidism.

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          Insulin-like growth factors and their binding proteins: biological actions.

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            Insulin-Like Growth Factor (IGF) System in Liver Diseases

            Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD), lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC) stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma). Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.
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              Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study.

              Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance. Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance. At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011). These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                March 2019
                15 March 2019
                : 98
                : 11
                : e14862
                Affiliations
                [a ]Department of Internal Medicine, National Taiwan University Hospital
                [b ]Graduate Institute of Clinical Medicine, College of Medicine
                [c ]Department of Medical Genetics, National Taiwan University Hospital
                [d ]Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
                Author notes
                []Correspondence: Fen-Yu Tseng, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan 100 (e-mail: fytseng@ 123456ntu.edu.tw ).
                Article
                MD-D-18-08018 14862
                10.1097/MD.0000000000014862
                6426554
                30882687
                6ee95006-e956-486c-9a9f-4b1ccc1120ca
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 30 October 2018
                : 17 January 2019
                : 15 February 2019
                Categories
                4300
                Research Article
                Observational Study
                Custom metadata
                TRUE

                euthyroidism,free thyroxine,hyperthyroidism,igf-1,logtsh,thyroid-stimulating hormone

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