Fibroblast Growth Factor 21 in Patients with Acromegaly

Abstract

Introduction The goal of the study was to investigate fibroblast growth factor-21 (FGF-21) levels in acromegalic patients in relation to the disease activity and to compare them with controls. Further, we aimed to evaluate the associations between FGF-21 and random growth hormone (GH), insulin-like growth factor-1 (IGF-1), metabolic and anthropometric parameters.

Materials and methods The study group consisted of 50 acromegalic patients divided into 3 subgroups on the basis of disease activity (AA – active acromegaly, CD – controlled disease, CA – cured acromegaly). 27 subjects were assigned to the control group (CG). Blood samples were obtained from all participants to assess FGF-21, GH, IGF-1, lipids, glucose and insulin levels. Body mass, body mass index and body composition were also evaluated.

Results There were no statistically significant differences in FGF-21 concentrations across all groups despite of subjects classification. FGF-21 correlated positively with random GH in the groups: CA, CD+CA, AA+CD+CA (r=0.48, p=0.049; r=0.39, p=0.023; r=0.33, p=0.02; respectively); with IGF-1 in the AA+CD+CA group (r=0.29, p=0.041); with triglycerides in the following groups: CD, CD+CA, AA+CD+CA (r=0.63, p=0.08; r=0.44, p=0.01; r=0.37, p=0.007; respectively) and with age in the CG and CD+CA groups (r=0.41, p=0.029; r=0.42, p=0.029; respectively). There were statistically significant negative correlations between FGF-21 and HDL-cholesterol levels in the groups: CD, CD+CA, AA+CD+CA (r=-0.53, p=0.03; r=-0.37, p=0.032; r=-0.29, p=0.036, respectively).

Conclusions FGF-21 levels were similar in patients with acromegaly compared to controls. However, our results indicate that FGF-21 may have a potential role in the development of acromegaly complications.

Key words

FGF-21 - acromegaly - GH - IGF-1 - body composition

• References

• 1 Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis 2008; 25: 3-17
• 2 Anthony JR, Ioachimescu AG. Acromegaly and bone disease. Curr Opin Endocrinol Diabetes Obes 2014; 21: 476-482
• 3 Bolanowski M, Ruchała M, Zgliczyński W. et al. Acromegaly-a novel view of the patient. Polish proposals for diagnostic and therapeutic procedures in the light of recent reports. Endokrynol Pol 2014; 65: 326-331
• 4 Han X, Chen C, Cheng G. et al. Serum fibroblast growth factor 21 levels are increased in atrial fibrillation patients. Cytokine 2015; 73: 176-180
• 5 Kim WJ, Kim SS, Lee HC. et al. Association between serum fibroblast growth factor 21 and coronary artery disease in patients with type 2 diabetes. J Korean Med Sci 2015; 30: 586-590
• 6 Woo YC, Xu A, Wang Y. et al Fibroblast growth factor 21 as an emerging metabolic regulator: Clinical perspectives. Clin Endocrinol (Oxf) 2013; 78: 489-496
• 7 Hansen JS, Clemmesen JO, Secher NH. et al. Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans. Mol Metab 2015; 4: 551-560
• 8 Kharitonenkov A, Shiyanova TL, Koester A. et al. FGF-21 as a novel metabolic regulator. J Clin Invest 2005; 115: 1627-1635
• 9 Kharitonenkov A, Wroblewski VJ, Koester A. et al. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 2007; 148: 774-781
• 10 Xu J, Lloyd DJ, Hale C. et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 2009; 58: 250-259
• 11 Li H, Fang Q, Gao F. et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatol 2010; 53: 934-940
• 12 Xiao Y, Xu A, Law LSC. et al. Distinct changes in serum fibroblast growth factor 21 levels in different subtypes of diabetes. J Clin Endocrinol Metab 2012; 97: 54-58
• 13 Dushay J, Chui PC, Gopalakrishnan GS. et al. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology 2010; 139: 456-463
• 14 Zhang X, Yeung DCY, Karpisek M. et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008; 57: 1246-1253
• 15 Ors D, Eroglu Altinova A, Yalçın MM. et al. Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus. Endokrynol Pol 2016; 67: 260-264
• 16 Chavez AO, Molina-Carrion M, Abdul-Ghani MA. et al. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care 2009; 32: 1542-1546
• 17 Sahin SB, Ayaz T, Cure MC. et al. Fibroblast growth factor 21 and its relation to metabolic parameters in women with polycystic ovary syndrome. Scand J Clin Lab Invest 2014; 74: 465-469
• 18 Kralisch S, Tönjes A, Krause K. et al. Fibroblast growth factor-21 serum concentrations are associated with metabolic and hepatic markers in humans. J Endocrinol 2013; 216: 135-143
• 19 Chen C, Cheung BMY, Tso AWK. et al. High plasma level of fibroblast growth factor 21 is an Independent predictor of type 2 diabetes: A 5.4-year population-based prospective study in Chinese subjects. Diabetes Care 2011; 34: 2113-2115
• 20 Bobbert T, Schwarz F, Fischer-Rosinsky A. et al. Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. Diabetes Care 2013; 36: 145-149
• 21 Lin Z, Wu Z, Yin X. et al. Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile. PLoS One 2010; 29: 15534
• 22 Mai K, Schwarz F, Bobbert T. et al. Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. Metab Clin Exp 2011; 60: 306-311
• 23 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: 219-228
• 24 Cheng X, Zhu B, Jiang F. et al. Serum FGF-21 levels in type 2 diabetic patients. Endocr Res 2011; 36: 142-148
• 25 Lee P, Linderman J, Smith S. et al. Fibroblast growth factor 21 (FGF21) and bone: Is there a relationship in humans?. Osteoporos Int 2013; 24: 3053-3057
• 26 Hanks LJ, Gutiérrez OM, Bamman MM. et al. Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals. J Clin Transl Endocrinol 2015; 2: 77-82
• 27 Møller N, Jørgensen JOL. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 2009; 30: 152-177
• 28 Mai K, Bobbert T, Groth C. et al. Physiological modulation of circulating FGF21: relevance of free fatty acids and insulin. Am J Physiol Endocrinol Metab 2010; 299: 126-130
• 29 Chen W, Hoo RL, Konishi M. et al. Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. J Biol Chem 2011; 286: 34559-34566