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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.
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.

Copyright © 2014 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( 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.

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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
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  • 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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