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Fibroblast growth factor 21 expressions in white blood cells and sera of patients with gestational diabetes mellitus during gestation and postpartum

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Abstract

Fibroblast growth factor 21 (FGF21), a recently discovered regulatory factor, plays an important role in glucose and lipid metabolism. In this study, we firstly found the FGF21 expression in white blood cells (WBCs). Then, we enrolled 51 women with gestational diabetes mellitus (GDM) and 50 pregnant women with normal blood glucose levels to determine the FGF21 levels in the WBCs and the sera at the 28th week of pregnancy, and tracked the dynamic changes of FGF21 in these women until the 7th day postpartum. Repeated Measures analysis of variance (ANOVA) revealed that there was a significant interaction effect between group and time on FGF21 levels (P < 0.05). FGF21 levels were significantly higher in the GDM patients than those in the controls at the 28th week of pregnancy. The 7th day after the delivery, the FGF21 levels decreased in the WBCs and the sera in both groups. The D values (the difference between pregnancy and postpartum) for FGF21 levels were significantly higher in the GDM group (P < 0.05). Serum FGF21 level during gestation positively correlated with leptin, triglyceride, and HDL-cholesterol, and FGF21 may act as a glucose and lipid metabolism compensatory regulatory factor to improve glucose and lipid metabolism during the period of pregnancy. Further, FGF21 level in the WBCs (during pregnancy and the D values for FGF21) was chiefly influenced by GDM.

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References

  1. American Diabetes Association, Standards of medical care in diabetes–2010. Diabetes Care 33, S11–S61 (2010)

    Article  PubMed Central  Google Scholar 

  2. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, B.E. Metzger, S.G. Gabbe, B. Persson, T.A. Buchanan, P.A. Catalano et al., International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33, 676–682 (2010)

    Article  PubMed Central  Google Scholar 

  3. HAPO Study Cooperative Research Group, B.E. Metzger, L.P. Lowe, A.R. Dyer, E.R. Trimble, U. Chaovarindr et al., Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358, 1991–2002 (2008)

    Article  Google Scholar 

  4. B.L. Silverman, T.A. Rizzo, N.H. Cho, B.E. Metzger, Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care 21, B142–B149 (1998)

    PubMed  Google Scholar 

  5. P.M. Catalano, J.P. Kirwan, S.M. De Haugel, J. King, Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr. 133(5), 1674S–1683S (2003)

    CAS  PubMed  Google Scholar 

  6. N.A. Beischer, P. Wein, M.T. Sheedy, B. Steffen, Identification and treatment of women with hyperglycaemia diagnosed during pregnancy can significantly reduce perinatal mortality rates. Aust. N. Z. J. Obstet. Gynaecol. 36(3), 239–247 (1996)

    Article  CAS  PubMed  Google Scholar 

  7. A.J. Lee, R.J. Hiscock, P. Wein, S.P. Walker, M. Permezel, Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care 30, 878–883 (2007)

    Article  CAS  PubMed  Google Scholar 

  8. D.J. Pettitt, R.G. Nelson, M.F. Saad, P.H. Bennett, W.C. Knowler, Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care 16(1), 310–314 (1993)

    Article  CAS  PubMed  Google Scholar 

  9. C. Kim, K.M. Newton, R.H. Knopp, Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 25(10), 1862–1868 (2002)

    Article  PubMed  Google Scholar 

  10. T. Nishimura, Y. Nakatake, M. Konishi, N. Itoh, Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim. Biophys. Acta 1492(1), 203–206 (2000)

    Article  CAS  PubMed  Google Scholar 

  11. M.D. Chau, J. Gao, Q. Yang, Z. Wu, J. Gromada, Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci U S A. 107, 12553–12558 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. B. Matuszek, M. Lenart-Lipińska, D. Duma, J. Solski, A. Nowakowski, Evaluation of concentrations of FGF-21-a new adipocytokine in type 2 diabetes. Endokrynol Pol. 61(1), 50–54 (2010)

    CAS  PubMed  Google Scholar 

  13. Y. Zhao, J.D. Dunbar, A. Kharitonenkov, FGF21 as a therapeutic reagent. Adv. Exp. Med. Biol. 728, 214–228 (2012)

    Article  CAS  PubMed  Google Scholar 

  14. A. Kharitonenkov, V.J. Wroblewski, A. Koester, Y.F. Chen, C.K. Clutinger, X.T. Tigno et al., The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148(2), 774–781 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. T. Coskun, H.A. Bina, M.A. Schneider, J.D. Dunbar, C.C. Hu, Y. Chen et al., Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149(12), 6018–6027 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. J. Xu, D.J. Lloyd, C. Hale, S. Stanislaus, M. Chen, G. Sivits et al., Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58(1), 250–259 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. S. Stein, H. Stepan, J. Kratzsch, M. Verlohren, H.J. Verlohren, K. Drynda et al., Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia. Metabolism 59(1), 33–37 (2010)

    Article  CAS  PubMed  Google Scholar 

  18. B.K. Tan, K. Sivakumar, M.F. Bari, M. Vatish, H.S. Randeva, Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes. PLoS ONE 8(6), e65254 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. H. Hsuchou, W. Pan, A.J. Kastin, The fasting polypeptide FGF21 can enter brain from blood. Peptides 28(12), 2382–2386 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. T.A. Buchanan, A. Xiang, S.L. Kjos, R. Watanabe, What is gestational diabetes? Diabetes Care 30, S105–S111 (2007)

    Article  CAS  PubMed  Google Scholar 

  21. W.W. Chen, L. Li, G.Y. Yang, K. Li, X.Y. Qi, W. Zhu et al., Circulating FGF-21 levels in normal subjects and in newly diagnose patients with Type 2 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes 116(1), 65–68 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. X. Zhang, D.C. Yeung, M. Karpisek, D. Stejskal, Z.G. Zhou, F. Liu et al., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 57(5), 1246–1253 (2008)

    Article  CAS  PubMed  Google Scholar 

  23. A.O. Chavez, M. Molina-Carrion, M.A. Abdul-Ghani, F. Folli, R.A. Defronzo, D. Tripathy, Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care 32(8), 1542–1546 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. S. Stein, A. Bachmann, U. Lössner, J. Kratzsch, M. Blüher, M. Stumvoll et al., Serum levels of the adipokine FGF21 depend on renal function. Diabetes Care 32(1), 126–128 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Nitert MD1, Barrett HL, Kubala MH, Scholz Romero K, Denny KJ, Woodruff TM, et al. Increased placental expression of Fibroblast Growth Factor 21 in gestational diabetes mellitus. J Clin Endocrinol Metab. 2014 Jan 16:jc20132581. [Epub ahead of print]

  26. N.F. Butte, Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am. J. Clin. Nutr. 71(5), 1256S–1261S (2000)

    CAS  PubMed  Google Scholar 

  27. E. Sivan, X. Chen, C.J. Homko, E.A. Reece, G. Boden, Longitudinal study of carbohydrate metabolism in healthy obese pregnant women. Diabetes Care 20(9), 1470–1475 (1997)

    Article  CAS  PubMed  Google Scholar 

  28. K.B. Lesser, M.W. Carpenter, Metabolic changes associated with normal pregnancy and pregnancy complicated by diabetes mellitus. Semin. Perinatol. 18(5), 399–406 (1994)

    CAS  PubMed  Google Scholar 

  29. N.F. Butte, J.M. Hopkinson, N. Mehta, J.K. Moon, E.O. Smith, Adjustments in energy expenditure and substrate utilization during late pregnancy and lactation. Am. J. Clin. Nutr. 69(2), 299–307 (1999)

    CAS  PubMed  Google Scholar 

  30. A. Kautzky-Willer, R. Prager, W. Waldhausl, G. Pacini, K. Thomaseth, O.F. Wagner et al., Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care 20(11), 1717–1723 (1997)

    Article  CAS  PubMed  Google Scholar 

  31. P.M. Catalano, E.D. Tyzbir, N.M. Roman, S.B. Amini, E.A. Sims, Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am. J. Obstet. Gynecol. 165(6), 1667–1672 (1991)

    Article  CAS  PubMed  Google Scholar 

  32. K. Eto, B. Tumenbayar, S. Nagashima, F. Tazoe, M. Miyamoto, M. Takahashi et al., Distinct association of serum FGF21 or adiponectin levels with clinical parameters in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 89(1), 52–57 (2010)

    Article  CAS  PubMed  Google Scholar 

  33. X. Zhang, D.C. Yeung, M. Karpisek, D. Stejskal, Z.G. Zhou, F. Liu et al., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 57(5), 1246–1253 (2008)

    Article  CAS  PubMed  Google Scholar 

  34. K. Eto, B. Tumenbayar, S. Nagashima, F. Tazoe, M. Miyamoto, M. Takahashi et al., Distinct association of serum FGF21 or adiponectin levels with clinical parameters in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 89(1), 52–57 (2010)

    Article  CAS  PubMed  Google Scholar 

  35. J. Hindricks, T. Ebert, A. Bachmann, S. Kralisch, U. Lössner, J. Kratzsch et al., Serum levels of fibroblast growth factor-21 are increased in chronic and acute renal dysfunction. Clin Endocrinol (Oxf). 80, 918–924 (2014)

    Article  CAS  PubMed  Google Scholar 

  36. H. Li, Y. Bao, A. Xu, X. Pan, J. Lu, H. Wu et al., Serum fibroblast growth factor 21 is associated with adverse lipid profiles and gamma-glutamyltransferase but not insulin sensitivity in Chinese subjects. J. Clin. Endocrinol. Metab. 94, 2151–2156 (2009)

    Article  CAS  PubMed  Google Scholar 

  37. J.C. Pickup, Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27(3), 813–823 (2004)

    Article  PubMed  Google Scholar 

  38. B. Vozarova, C. Weyer, R.S. Lindsay, R.E. Pratley, C. Bogardus, P.A. Tataranni, High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51(2), 455–461 (2002)

    Article  CAS  PubMed  Google Scholar 

  39. G.P. Sacks, K. Studena, K. Sargent, C.W. Redman, Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am. J. Obstet. Gynecol. 179(1), 80–86 (1998)

    Article  CAS  PubMed  Google Scholar 

  40. M.S. Lee, S.E. Choi, E.S. Ha, S.Y. An, T.H. Kim, S.J. Han et al., Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB. Metabolism 61(8), 1142–1151 (2012)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study was supported by the National Natural Science Foundation of China (No. 81172741 and 30972537).

Conflict of interest

The authors declare that there is no conflict of interest in this study.

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Authors and Affiliations

  1. School of Life Science, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China

    Si-ming Li, Wen-fei Wang, Lei Ma, Ying An, Wen-juan Xu, Yin-hang Yu & De-shan Li

  2. Harbin University of Commerce, Harbin, 150028, China

    Si-ming Li

  3. Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, 150030, China

    Li-hong Zhou

  4. College of life sciences, University of Chinese Academy of Sciences, Beijing, 100049, China

    Tian-he Li

  5. Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin, 150030, China

    Yan Liu

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  1. Si-ming Li
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Li, Sm., Wang, Wf., Zhou, Lh. et al. Fibroblast growth factor 21 expressions in white blood cells and sera of patients with gestational diabetes mellitus during gestation and postpartum. Endocrine 48, 519–527 (2015). https://doi.org/10.1007/s12020-014-0309-8

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  • DOI: https://doi.org/10.1007/s12020-014-0309-8

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