Association of fibroblast growth factor 21 with oxidative stress and lipid profile in type 2 diabetes

Vineetha K. R., Santha K., Inmozhi R., Periyasamy S., Kanakasabai G., Baskaran K.


Background: Cardiovascular disease is the most prevalent cause of morbidity and mortality in diabetic patients. Fibroblast growth factor 21 (FBG 21) is an endocrine factor that regulates glucose and lipid metabolism, insulin resistance, and obesity. Blood levels of FGF21 are elevated in patients with atherosclerosis, macrovascular, and microvascular complications of diabetes, possibly due to a compensatory up regulation. Studies reported that FGF21 is an important regulator of mitochondrial and oxidative stress. The role of FGF21 in chronic diseases and the diminished oxidative stress observed with anti-diabetic therapy has been the target of new studies. Current study aimed to evaluate serum FGF21 levels and its association with oxidative stress and lipid profile levels in type 2 diabetic patients.

Methods: 100 controls and 100 diabetic patients on oral hypoglycemic drugs between 35-55 years of age without any cardiac, renal, liver, and thyroid dysfunction were selected for this study. Oxidative stress (MDA), total antioxidant status (FRAP), and FGF21 were measured. FGF21 was analyzed by ELISA methods. Serum MDA was assessed by the method of Yagi  serum total antioxidant status was measured by the method of Benzie et al.

Results: FGF21 level was increased in diabetic patients compared with controls. There was a significant positive correlation of FGF21 with MDA (r=0.875, p<0.01) and negative correlation with FRAP observed (r= -0.867 p<0.01). There was also positive correlation of FGF21 with total cholesterol (r=0.499, p<0.01), triglycerides (r=0.648, p<0.01), LDL-cholesterol (r=0.337, p<0.01) and negative correlation with HDL-cholesterol (r= -0.172, p<0.05) were observed.

Conclusions: Increased oxidative stress and decreased antioxidant status were observed in diabetics. This could be due to dyslipidemia and increased generation of free radicals. High levels of FGF21 observed in our study might represent its resistant state and the compensatory response to maintain metabolic homeostasis. Further studies are needed to explore the role of FGF21 as a novel marker in predicting cardiovascular risk in diabetic patients.


Fibroblast growth factor, Malondialdehyde, Lipid profile, Type 2 diabetes mellitus

Full Text:



Wu F, Wang B, Zhang S, Shi L, Wang Y, Xiong R, et al. FGF21 ameliorates diabetic cardiomyopathy by activating the AMPK-paraoxonase 1 signaling axis in mice. Clin Sci. 2017;131(15):1877-93.

Verhulst MJL, Loos BG, Gerdes VEA, Teeuw WJ. Evaluating all potential oral complications of diabetes mellitus. Front Endocrinol. 2019;10(56):1-49.

Raedschelders K, Ansley DM, Chen DDY. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacol Ther. 2012;133(2):230-55.

Gómez-Sámano MÁ, Grajales-Gómez M, Zuarth-Vázquez JM, Navarro-Flores MF, Martínez-Saavedra M. Fibroblast growth factor 21 and its novel association with oxidative stress. Redox Biol. 2017; 11(2016):335-41.

Ren Y, Li Y, Yan J, Ma M, Zhou D, Xue Z, et al. Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis. Sci Rep. 2017;7(1):1-12.

Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of oxidative stress during diabetes mellitus. J Biomark. 2013;2013:378790.

Sharma R, Satyanarayana P, Pallavi A, Kumar S. Circulating serum adiponectin and oxidative stress biomarkers in prediabetes and type 2 diabetes mellitus patients. Asian J Pharm Clin Res. 2019;12 (12):58-60.

Kim CS, Joe Y, Choi HS, Back SH, Park JW, Chung HT, et al. Deficiency of fibroblast growth factor 21 aggravates obesity-induced atrophic responses in skeletal muscle. J Inflamm. 2019;16:17.

Chen HF, Wu F, Lu N, Zheng WP, Lin KY. Decreased levels of serum fibroblast growth factor 21 in Chinese patients with coronary artery disease. Int J Clin Exp Pathol. 2016;9(9):9625-30.

Struik D, Dommerholt MB, Jonker JW. Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application. Curr Opin Lipidol. 2019;30(3):235-43.

Chen H, Lu N, Zheng M. A high circulating FGF21 level as a prognostic marker in patients with acute myocardial infarction. Am J Transl Res. 2018;10(9): 2958-66.

Tanajak P, Chattipakorn SC, Chattipakorn N. Effects of fibroblast growth factor 21 on the heart. J Endocrinol. 2015;227(2):R13-30.

Jin L, Lin Z, Xu, A. Fibroblast growth factor 21 protects against atherosclerosis via fine-tuning the multiorgan crosstalk. Diab Metab J. 2016;40(1):22-31.

Yagi K. Lipid peroxides and human diseases. Chem Phys Lipids. 1987;45(2-4):337-51.

Benzi IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem. 1996;239:70-6.

Hauner H. Obesity and diabetes. In: Holt RIG, Cockram CS, Flyvbjerg A, eds. Textbook of diabetes. 4th ed. United States: Wiley-Blackwell; 2010:227.

Vasanthakumar J, Kambar S. Prevalence of obesity among type 2 diabetes mellitus patients in urban areas of Belagavi. Indian J Health Sci Biomed Res. 2020;13:21-7.

Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study. BMJ. 1998;316(7134):823-28.

Vergès B. New insight into the pathophysiology of lipid abnormalities in type 2 diabetes. Diabetes Metab. 2005;31(5):429-39.

Staiger H, Keuper M, Berti L, Hrabe de Angelis M, Häring HU. Fibroblast Growth Factor 21-Metabolic Role in Mice and Men. Endocr Rev. 2017;38(5):468-88.

Tezze C, Romanello V, Sandri M. FGF21 as Modulator of Metabolism in Health and Disease. Front Physiol. 2019;10:419.

Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78: 223-41.

Kohara M, Masuda T, Shiizaki K, Akimoto T, Watanabe Y, Honma S, Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS ONE. 2017;12(6):1-14.

Sireesha K, Sailaja RP. Oxidative stress and diabetes: An overview. Asian J Pharm Clin Res. 2015;8(1):15-9.

Ying L, Li N, He Z, Zeng X, Nan Y, Chen J, et al. Fibroblast growth factor 21 Ameliorates diabetes-induced endothelial dysfunction in mouse aorta via activation of the CaMKK2/AMPKα signaling pathway. Cell Death Dis. 2019;10(9):665.

Planavila A, Redondo-Angulo I, Villarroya F. FGF21 and Cardiac Physiopathology. Front Endocrinol (Lausanne). 2015;6:133.