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Is GDF15 a Novel Biomarker to Predict the Development of Prediabetes or Diabetes?

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D I A B E T E S & M E T A B O L I S M J O U R N A L

his is an Open Access article distributed under the terms of the Creative Commons At-tribution 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.

Copyright © 2014 Korean Diabetes Association http://e-dmj.org Diabetes Metab J 2014;38:437-438

Is GDF15 a Novel Biomarker to Predict the

Development of Prediabetes or Diabetes?

Kyu Yeon Hur

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

E-mail: ky.hur@samsung.com

Growth diferentiation factor 15 (GDF15) was discovered as a divergent member of the transforming growth factor β (TGF-β) superfamily. GDF15 was cloned independently in diferent lab-oratories and is therefore also known as diferent names includ-ing macrophage inhibitory cytokine-1 [1], nonsteroidal anti-in-lammatory drug-activated gene-1 [2], placental bone morpho-genetic protein B [3], and placental transforming growth factor

β [4]. It is expressed in various cells including macrophages, car-diomyocytes, adipocytes, smooth muscle cells, and endothelial cells.

In terms of inflammation, GDF15 has anti-inflammatory characteristics. Proinlammatory cytokines like interleukin 1β (IL-1β) and TNF-α stimulates GDF15 [1], which in turn stimu-lates adiponectin. Adiponectin is a well-known anti-inlamma-tory protein whose circulating levels are decreased before type 2 diabetes [5]. his inding suggests that GDF15 may also play a role in compensatory anti-inlammatory response in type 2 dia-betes.

GDF15 showed some conlicting results in obesity and weight loss. Circulating levels of GDF15 showed a positive correlation with obesity or body mass index (BMI) in several previous stud-ies [6,7]. However, Framingham Ofspring 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 ater 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 Sub-jects 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 se-rum level of GDF15 had a positive correlation with impaired fast-ing 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 ei-cacy of GDF15 as a biomarker to detect prediabetes instead of oral glucose tolerance test or hemoglobin A1c should be con-irmed in a prospective study using oral glucose tolerance test.

CONFLICTS OF INTEREST

No potential conlict of interest relevant to this article was re-ported.

REFERENCES

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;94:11514-9.

2. Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE. Cyclooxy-genase inhibitors regulate the expression of a TGF-beta

super-Editorial

Others

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Hur KY

Diabetes Metab J 2014;38:437-438 http://e-dmj.org family member that has proapoptotic and antitumorigenic

ac-tivities. Mol Pharmacol 2001;59:901-8.

3. Hromas R, Huford M, Sutton J, Xu D, Li Y, Lu L. PLAB, a novel placental bone morphogenetic protein. Biochim Biophys Acta 1997;1354:40-4.

4. Lawton LN, Bonaldo MF, Jelenc PC, Qiu L, Baumes SA, Mar-celino RA, de Jesus GM, Wellington S, Knowles JA, Warburton D, Brown S, Soares MB. Identiication of a novel member of the TGF-beta superfamily highly expressed in human placenta. Gene 1997;203:17-26.

5. Ding Q, Mracek T, Gonzalez-Muniesa P, Kos K, Wilding J, Tray-hurn P, Bing C. Identiication of macrophage inhibitory cyto-kine-1 in adipose tissue and its secretion as an adipokine by hu-man adipocytes. Endocrinology 2009;150:1688-96.

6. Carstensen M, Herder C, Brunner EJ, Strassburger K, Tabak AG, Roden M, Witte DR. Macrophage inhibitory cytokine-1 is in-creased 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;162:913-7.

7. Kempf T, Guba-Quint A, Torgerson J, Magnone MC, Haeliger C, Bobadilla M, Wollert KC. Growth diferentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial. Eur J Endocrinol 2012;167:671-8.

8. Ho JE, Mahajan A, Chen MH, Larson MG, McCabe EL, Ghor-bani 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;58:1582-91. 9. Vila G, Riedl M, Anderwald C, Resl M, Handisurya A, Clodi M,

Prager G, Ludvik B, Krebs M, Luger A. he relationship between insulin resistance and the cardiovascular biomarker growth difer-entiation factor-15 in obese patients. Clin Chem 2011;57:309-16. 10. Hong JH, Chung HK, Park HY, Joung KH, Lee JH, Jung JG, Kim

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