The relationship between fibroblast growth factor 21 with biochemical parameters, anthropometric measurements and dietary intake in type 2 diabetic patients

Main Article Content

Elham Mirzaee
Laleh Payahoo
Zohreh Ghoreishi
Hamireza Razmi
Mehdi Amirpour

Keywords

Type 2 diabetes mellitus; Dietary intake; FGF-21; Interleukin-6; TNF-α

Abstract

Background: Fibroblast growth factor-21 (FGF-21), as a novel cytokine, plays an important role in the improvement of glucose and lipid metabolism via different metabolic pathways. Therefore, the aim of this study to investigate the relationship between FGF-21 and metabolic profile parameters in patients with type 2 diabetes mellitus (T2DM) compared to healthy controls.


Methods: In this cross-sectional study, 85 patients with T2DM and 79 healthy subjects were recruited. Anthropometric measurements, dietary intake and biochemical measurements were assessed for all participants.


Results: Serum levels of FGF-21 were negatively associated with hip circumference (HC) (β= -0.267, p= 0.038) and dietary proteins (β = -0.273, p= 0.005) in healthy subjects. Moreover, dietary carbohydrate intake was inversely associated with FGF-21 (β= -0.183, p=0.041) in the total population. Also, serum levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and fasting blood sugar (FBS) in diabetic patients were significantly higher than those in healthy subjects (p<0.05); However surprisingly, triglyceride (TG) and fasting insulin levels were significantly higher in healthy subjects (p<0.05). Tumor necrosis factor-α (TNF- α) was positively associated with LDL-C in healthy subjects as well as FBS and hemoglobin A1c (HbA1c) in all participants. Serum TNF-α levels had a significant positive association with body mass index (BMI) (β= 0.303, p= 0.004) and HC (β= 0.294, p= 0.012) in patients with T2DM.


Conclusions: Our findings revealed that dietary intake of protein and carbohydrates were inversely associated with serum levels of FGF-21. Therefore, more detailed studies are needed in order to reach a robust conclusion.

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References

1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88-98. doi: 10.1038/nrendo.2017.151.
2. American Diabetes Association. Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care. 2018 May;41(5):917-928. doi: 10.2337/dci18-0007.
3. Diabetes Canada Clinical Practice Guidelines Expert Committee; Punthakee Z, Goldenberg R, Katz P. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes. 2018 Apr;42 Suppl 1:S10-S15. doi: 10.1016/j.jcjd.2017.10.003.
4. Latko M, Czyrek A, Porębska N, Kucińska M, Otlewski J, Zakrzewska M, Opaliński Ł. Cross-Talk between Fibroblast Growth Factor Receptors and Other Cell Surface Proteins. Cells. 2019 May 14;8(5):455. doi: 10.3390/cells8050455.
5. Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015 May-Jun;4(3):215-66. doi: 10.1002/wdev.
6. Lin X, Liu YB, Hu H. Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues. Biomed Rep. 2017 May;6(5):495-502. doi: 10.3892/br.2017.890.
7. Davoodi SH, Hajimiresmaiel SJ, Ajami M, et al. Caffeine treatment prevented from weight regain after calorie shifting diet induced weight loss. Iran J Pharm Res. 2014 Spring;13(2):707-18. PMID: 25237367.
8. Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78:223-41. doi: 10.1146/annurev-physiol-021115-105339.
9. Woo YC, Lee CH, Fong CH, et al. Serum fibroblast growth factor 21 is a superior biomarker to other adipokines in predicting incident diabetes. Clin Endocrinol (Oxf). 2017 Jan;86(1):37-43. doi: 10.1111/cen.13229.
10. Li H, Wu G, Fang Q, et al. Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat. Nat Commun. 2018 Jan 18;9(1):272. doi: 10.1038/s41467-017-02677-9.
11. Novotny D, Vaverkova H, Karasek D, et al. Evaluation of total adiponectin, adipocyte fatty acid binding protein and fibroblast growth factor 21 levels in individuals with metabolic syndrome. Physiol Res. 2014;63(2):219-28. doi: 10.33549/physiolres.932602.
12. Gao RY, Hsu BG, Wu DA, Hou JS, Chen MC. Serum Fibroblast Growth Factor 21 Levels Are Positively Associated with Metabolic Syndrome in Patients with Type 2 Diabetes. Int J Endocrinol. 2019 Sep 10;2019:5163245. doi: 10.1155/2019/5163245.
13. Salminen A, Kauppinen A, Kaarniranta K. FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process. J Mol Med (Berl). 2017 Feb;95(2):123-131. doi: 10.1007/s00109-016-1477-1.
14. Strowski MZ. Impact of FGF21 on glycemic control. Horm Mol Biol Clin Investig. 2017 Jun 3;30(2):/j/hmbci.2017.30.issue-2/hmbci-2017-0001/hmbci-2017-0001.xml. doi: 10.1515/hmbci-2017-0001.
15. Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. 2020 Nov;16(11):654-667. doi: 10.1038/s41574-020-0386-0.
16. Ayatollahi SA, Ajami M, Reyhanfard H, Asadi Y, Nassiri-Kashani M, Rashighi Firoozabadi M, Davoodi SH, Habibi E, Pazoki-Toroudi H. BCL-2 and Bax Expression in Skin Flaps Treated with Finasteride or Azelaic Acid. Iran J Pharm Res. 2012 Fall;11(4):1285-90. PMID: 24250563.
17. Gómez-Ambrosi J, Pastor C, Salvador J, et al. Influence of waist circumference on the metabolic risk associated with impaired fasting glucose: effect of weight loss after gastric bypass. Obes Surg. 2007 May;17(5):585-91. doi: 10.1007/s11695-007-9101-7. Erratum in: Obes Surg. 2007 Jul;17(7):996.
18. Panahi Y, Bonakdaran S, Yaghoubi MA, Keramati MR, Haratian M, Sahebkar A. Serum levels of fibroblast growth factor 21 in type 2 diabetic patients. Acta Endocrinol (Buchar). 2016 Jul-Sep;12(3):257-261. doi: 10.4183/aeb.2016.257.
19. Cheng X, Zhu B, Jiang F, Fan H. Serum FGF-21 levels in type 2 diabetic patients. Endocr Res. 2011;36(4):142-8. doi: 10.3109/07435800.2011.558550.
20. Jin QR, Bando Y, Miyawaki K, et al. Correlation of fibroblast growth factor 21 serum levels with metabolic parameters in Japanese subjects. J Med Invest. 2014;61(1-2):28-34. doi: 10.2152/jmi.61.28.
21. Zhang X, Yeung DC, Karpisek M, et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes. 2008 May;57(5):1246-53. doi: 10.2337/db07-1476. Epub 2008 Feb 5. Erratum in: Diabetes. 2019 Jan;68(1):235.
22. Zhang X, Yang L, Xu X, et al. A review of fibroblast growth factor 21 in diabetic cardiomyopathy. Heart Fail Rev. 2019 Nov;24(6):1005-1017. doi: 10.1007/s10741-019-09809-x.
23. Wang N, Xu TY, Zhang X, et al. Improving hyperglycemic effect of FGF-21 is associated with alleviating inflammatory state in diabetes. Int Immunopharmacol. 2018 Mar;56:301-309. doi: 10.1016/j.intimp.2018.01.048.
24. Lee MS, Choi SE, Ha ES, et al. Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB. Metabolism. 2012 Aug;61(8):1142-51. doi: 10.1016/j.metabol.2012.01.012.
25. Bhowmik B, Siddiquee T, Mujumder A, et al. Serum lipid profile and its association with diabetes and prediabetes in a rural Bangladeshi population. Int J Environ Res Public Health. 2018 Sep 6;15(9):1944. doi: 10.3390/ijerph15091944.
26. Massing MW, Henley NS, Carter-Edwards L, Schenck AP, Simpson RJ Jr. Lipid testing among patients with diabetes who receive diabetes care from primary care physicians. Diabetes Care. 2003 May;26(5):1369-73. doi: 10.2337/diacare.26.5.1369.
27. Jabbari M, Barati M, Fathollahi A, et al. Can oral tolerance explain the inconsistencies associated with total dietary diversity and colon cancer? A mechanistic systematic review. Nutr Cancer. 2021;73(11-12):2101-2112. doi: 10.1080/01635581.2020.1819349.
28. Eller-Vainicher C, Cairoli E, Grassi G, et al. Pathophysiology and management of type 2 diabetes mellitus bone fragility. J Diabetes Res. 2020 May 22;2020:7608964. doi: 10.1155/2020/7608964.
29. Barati M, Jabbari M, Nickho H, et al. Regulatory T cells in bioactive peptides-induced oral tolerance; a two-edged sword related to the risk of chronic diseases: a systematic review. Nutr Cancer. 2021;73(6):956-967. doi: 10.1080/01635581.2020.1784442.
30. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014 Aug;105(2):141-50. doi: 10.1016/j.diabres.2014.04.006.
31. Nimkuntod P, Tongdee P. Association between subclinical atherosclerosis among hyperlipidemia and healthy subjects. J Med Assoc Thai. 2015 May;98 Suppl 4:S51-7. PMID: 26201134.
32. Augustemak de Lima LR, Petroski EL, Moreno YMF, et al. Dyslipidemia, chronic inflammation, and subclinical atherosclerosis in children and adolescents infected with HIV: The PositHIVe Health Study. PLoS One. 2018 Jan 10;13(1):e0190785. doi: 10.1371/journal.pone.0190785.
33. Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2016 Feb;92(1084):63-9. doi: 10.1136/postgradmedj-2015-133281.
34. Reinehr T, Woelfle J, Wunsch R, Roth CL. Fibroblast growth factor 21 (FGF-21) and its relation to obesity, metabolic syndrome, and nonalcoholic fatty liver in children: a longitudinal analysis. J Clin Endocrinol Metab. 2012 Jun;97(6):2143-50. doi: 10.1210/jc.2012-1221.
35. Chalvon-Demersay T, Even PC, Tomé D, et al. Low-protein diet induces, whereas high-protein diet reduces hepatic FGF21 production in mice, but glucose and not amino acids up-regulate FGF21 in cultured hepatocytes. J Nutr Biochem. 2016 Oct;36:60-67. doi: 10.1016/j.jnutbio.2016.07.002.
36. Lundsgaard AM, Fritzen AM, Sjøberg KA, et al. Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates. Mol Metab. 2016 Nov 16;6(1):22-29. doi: 10.1016/j.molmet.2016.11.001.