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Others Is GDF15 a Novel Biomarker to Predict the Development of Prediabetes or Diabetes?
Kyu Yeon Hur
Diabetes & Metabolism Journal 2014;38(6):437-438.
DOI: https://doi.org/10.4093/dmj.2014.38.6.437
Published online: December 15, 2014
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Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Corresponding author: Kyu Yeon Hur. Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea. ky.hur@samsung.com

Copyright © 2014 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Growth differentiation factor 15 (GDF15) was discovered as a divergent member of the transforming growth factor β (TGF-β) superfamily. GDF15 was cloned independently in different laboratories and is therefore also known as different names including macrophage inhibitory cytokine-1 [1], nonsteroidal anti-inflammatory drug-activated gene-1 [2], placental bone morphogenetic protein B [3], and placental transforming growth factor β [4]. It is expressed in various cells including macrophages, cardiomyocytes, adipocytes, smooth muscle cells, and endothelial cells.
In terms of inflammation, GDF15 has anti-inflammatory characteristics. Proinflammatory cytokines like interleukin 1β (IL-1β) and TNF-α stimulates GDF15 [1], which in turn stimulates adiponectin. Adiponectin is a well-known anti-inflammatory protein whose circulating levels are decreased before type 2 diabetes [5]. This finding suggests that GDF15 may also play a role in compensatory anti-inflammatory response in type 2 diabetes.
GDF15 showed some conflicting results in obesity and weight loss. Circulating levels of GDF15 showed a positive correlation with obesity or body mass index (BMI) in several previous studies [6,7]. However, Framingham Offspring study reported that GDF15 had no association with BMI [8], and other studies even demonstrated that increased levels of GDF15 was in parallel with weight loss after bariatric surgery [9].
In glucose metabolism, GDF15 had similar characteristics to IL-1 receptor antagonist and TGF-β1 rather than adiponectin. Previous representative studies, such as Whitehall II cohort study [6] and the XENical in the prevention of Diabetes in Obese Subjects study [7] showed that higher circulating levels of GDF15 were associated with higher risk of type 2 diabetes.
Hong et al. [10] showed that GDF15 had a positive correlation with insulin resistance independent of age and BMI, and the serum level of GDF15 had a positive correlation with impaired fasting glucose and type 2 diabetes and insisted that GDF15 may be a novel biomarker for detecting impaired fasting glucose. However, this is a cross-sectional study, not a prospective study. So the efficacy of GDF15 as a biomarker to detect prediabetes instead of oral glucose tolerance test or hemoglobin A1c should be confirmed in a prospective study using oral glucose tolerance test.

No potential conflict of interest relevant to this article was reported.

  • 1. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, Zhang HP, Donnellan M, Mahler S, Pryor K, Walsh BJ, Nicholson RC, Fairlie WD, Por SB, Robbins JM, Breit SN. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci U S A 1997;94:11514-11519. PubMedPMC
  • 2. Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol 2001;59:901-908. ArticlePubMed
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  • 4. Lawton LN, Bonaldo MF, Jelenc PC, Qiu L, Baumes SA, Marcelino RA, de Jesus GM, Wellington S, Knowles JA, Warburton D, Brown S, Soares MB. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta. Gene 1997;203:17-26. ArticlePubMed
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  • 6. Carstensen M, Herder C, Brunner EJ, Strassburger K, Tabak AG, Roden M, Witte DR. Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study. Eur J Endocrinol 2010;162:913-917. ArticlePubMed
  • 7. Kempf T, Guba-Quint A, Torgerson J, Magnone MC, Haefliger C, Bobadilla M, Wollert KC. Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial. Eur J Endocrinol 2012;167:671-678. ArticlePubMed
  • 8. Ho JE, Mahajan A, Chen MH, Larson MG, McCabe EL, Ghorbani A, Cheng S, Johnson AD, Lindgren CM, Kempf T, Lind L, Ingelsson E, Vasan RS, Januzzi J, Wollert KC, Morris AP, Wang TJ. Clinical and genetic correlates of growth differentiation factor 15 in the community. Clin Chem 2012;58:1582-1591. ArticlePubMedPMCPDF
  • 9. Vila G, Riedl M, Anderwald C, Resl M, Handisurya A, Clodi M, Prager G, Ludvik B, Krebs M, Luger A. The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients. Clin Chem 2011;57:309-316. ArticlePubMedPDF
  • 10. Hong JH, Chung HK, Park HY, Joung KH, Lee JH, Jung JG, Kim KS, Kim HJ, Ku BJ, Shong M. GDF15 is a novel biomarker for impaired fasting glucose. Diabetes Metab J 2014;38:472-479.ArticlePubMedPMC

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      Is GDF15 a Novel Biomarker to Predict the Development of Prediabetes or Diabetes?
      Diabetes Metab J. 2014;38(6):437-438.   Published online December 15, 2014
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    Hur KY. Is GDF15 a Novel Biomarker to Predict the Development of Prediabetes or Diabetes?. Diabetes Metab J. 2014;38(6):437-438.
    DOI: https://doi.org/10.4093/dmj.2014.38.6.437.

    Diabetes Metab J : Diabetes & Metabolism Journal