The relationship of Growth differentiation factor-15 with renal damage and dyslipidemia in non-albuminuric and albuminuric Type-2 Diabetes Mellitus

Main Article Content

Hasan Esat Yücel
Bilal İlanbey


Objective: Aim of this study is to investigate the correlation of Growth differentiation factor-15  with renal damage and dyslipidemia in Type-2 Diabetes Mellitus.

Material and Method: The study was conducted prospectively with patients diagnosed with Type-2 Diabetes Mellitus. Two groups were formed as non-albuminuric (n:47) and albuminuric (n:24). Age, gender, Growth differentiation factor-15, glycemic index, lipid panel, glomerular filtration rate, complete blood count, urine albumin/creatin and urine protein/creatin of the groups were compared, and their correlations were examined.

Results: Growth differentiation factor-15, age, and hemoglobin A1c were found to be higher in the albuminuric group, and hemoglobin and hematocrit levels were found to be lower. A positive correlation of Growth differentiation factor-15 with spot urine albumin/creatin and protein/creatin was observed in the albuminuric group. In the non-albuminuric group, positive correlation was observed with Triglyceride and a negative correlation with high-density lipoprotein cholesterol. Negative correlation of Growth differentiation factor-15 glomerular filtration rate was detected in all participants.

Conclusions: Growth differentiation factor-15 has been found positively associated with albuminuria and high triglyceride levels in Type-2 Diabetes Mellitus. It is negatively correlated with glomerular filtration rate and high-density lipoprotein cholesterol. It is strongly associated with renal damage and dyslipidemia.


Download data is not yet available.

Article Details

How to Cite
Yücel, H. E., & İlanbey, B. . (2022). The relationship of Growth differentiation factor-15 with renal damage and dyslipidemia in non-albuminuric and albuminuric Type-2 Diabetes Mellitus. Medical Science and Discovery, 9(6), 334–339.
Research Article
Received 2022-05-24
Accepted 2022-06-09
Published 2022-06-10


Unsicker K, Spittau B, Krieglstein K. The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1. Cytokine Growth Factor Rev. 2013 ;24(4):373-84.

Wollert KC, Kempf T, Wallentin L. Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease. Clin Chem. 2017 ;63(1):140-151.

Shin MY, Kim JM, Kang YE, Kim MK, Joung KH, Lee JH, et al. Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. J Korean Med Sci. 2016 ;31(9):1413-8.

Adela R, Banerjee SK. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J Diabetes Res. 2015;2015:490842.

Dostálová I, Roubícek T, Bártlová M, Mráz M, Lacinová Z, Haluzíková D, et al. Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet. Eur J Endocrinol. 2009 ;161(3):397-404.

Ding Q, Mracek T, Gonzalez-Muniesa P, Kos K, Wilding J, Trayhurn P, et al.Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology. 2009 ;150(4):1688-96.

Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015;58(5):886-99.

Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia. 2003 ;46(6):733-49.

Tziomalos K, Athyros VG, Karagiannis A, Kolovou GD, Mikhailidis DP. Triglycerides and vascular risk: insights from epidemiological data and interventional studies. Curr Drug Targets. 2009 ;10(4):320-7.

Desmedt S, Desmedt V, De Vos L, Delanghe JR, Speeckaert R, Speeckaert MM. Growth differentiation factor 15: A novel biomarker with high clinical potential. Crit Rev Clin Lab Sci. 2019 ;56(5):333-350.

Kempf T, Guba-Quint A, Torgerson J, Magnone MC, Haefliger C, Bobadilla M,et al. Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese non-diabetic individuals: results from the XENDOS trial. Eur J Endocrinol. 2012 ;167(5):671-8.

Carballo-Casla A, García-Esquinas E, Buño-Soto A, Struijk EA, López-García E, et al. Metabolic syndrome and Growth Differentiation Factor 15 in older adults. Geroscience. 2022 ;44(2):867-880.

Carlsson AC, Nowak C, Lind L, Östgren CJ, Nyström FH, Sundström J, et al. Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach. Ups J Med Sci. 2020 ;125(1):37-43.

Chung JO, Chung MY, Park SY, Cho DH, Chung DJ. Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria. J Diabetes Complications. 2021 ;35(4):107849.

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 5;150(9):604-12.

Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. Am J Kidney Dis. 2018 ;71(6):884-895

Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ. Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury. Mol Cell Biol. 2000 ;20(10):3742-51.

Simonson MS, Tiktin M, Debanne SM, Rahman M, Berger B, Hricik D,et al. The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study. Am J Physiol Renal Physiol. 2012 1;302(7):F820-9.

Agarwal RG, Khokhar M, Purohit P, Modi A, Bajpai NK, Bohra GK,et al. A clinical and in-silico study of MicroRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy. Minerva Endocrinol (Torino). 2022 Feb 1. Epub ahead of print.

Simm A, Nass N, Bartling B, Hofmann B, Silber RE, Navarrete Santos A. Potential biomarkers of ageing. Biol Chem. 2008 ;389(3):257-65.

Bilson J, Scorletti E, Bindels LB, Afolabi PR, Targher G, Calder PC, et al. Growth differentiation factor-15 and the association between type 2 diabetes and liver fibrosis in NAFLD. Nutr Diabetes. 2021 18;11(1):32.

Li H, Gao F, Xue Y, Qian Y. [Value of plasma growth differentiation factor-15 in diagnosis and evaluation of type 2 diabetic nephropathy]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 ;34(3):387-90. Chinese

Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2015 9;5(1):49-56.

Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011 ;17(5):581-8.

Ito K, Yokota S, Watanabe M, Inoue Y, Takahashi K, Himuro N,et al. Anemia in Diabetic Patients Reflects Severe Tubulointerstitial Injury and Aids in Clinically Predicting a Diagnosis of Diabetic Nephropathy. Intern Med. 2021;60(9):1349-1357.

El-Achkar TM, Ohmit SE, McCullough PA, Crook ED, Brown WW, Grimm R, et al. Kidney Early Evaluation Program. Higher prevalence of anemia with diabetes mellitus in moderate kidney insufficiency: The Kidney Early Evaluation Program. Kidney Int. 2005 ;67(4):1483-8.

Rabelink TJ, de Zeeuw D. The glycocalyx--linking albuminuria with renal and cardiovascular disease. Nat Rev Nephrol. 2015 ;11(11):667-76.

Ding Q, Mracek T, Gonzalez-Muniesa P, Kos K, Wilding J, Trayhurn P, et al. Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology. 2009 ;150(4):1688-96.

Shimano M, Ouchi N, Walsh K. Cardiokines: recent progress in elucidating the cardiac secretome. Circulation. 2012;20;126(21):e327-32.

Ho JE, Mahajan A, Chen MH, Larson MG, McCabe EL, Ghorbani A,et al. Clinical and genetic correlates of growth differentiation factor 15 in the community. Clin Chem. 2012 ;58(11):1582-91.

Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med. 2016 ;26(4):364-73.

Bermúdez B, López S, Pacheco YM, Villar J, Muriana FJ, Hoheisel JD,et al. Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery. Cardiovasc Res. 2008;15;79(2):294-303.

Xu X, Li Z, Gao W. Growth differentiation factor 15 in cardiovascular diseases: from bench to bedside. Biomarkers. 2011;16(6):466-75.

Kim JM, Back MK, Yi HS, Joung KH, Kim HJ, Ku BJ. Effect of Atorvastatin on Growth Differentiation Factor-15 in Patients with Type 2 Diabetes Mellitus and Dyslipidemia. Diabetes Metab J. 2016 ;40(1):70-8.