Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls
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Fibroblast growth factor-21 (FGF-21) appears to have an important role in glucose and lipid metabolism. FGF-21 secretion is mainly determined by nutritional status. The aim of this study was to measure basal and postprandial FGF-21 and postprandial change of FGF-21 concentration in type 1 diabetes mellitus (T1DM) patients and in healthy controls, and to investigate the differences between the groups. The cross-sectional study included 30 C-peptide negative T1DM patients, median age 37 years (20–59), disease duration 22 years (3–45), and nine healthy controls, median age 30 years (27–47). Basal and postprandial FGF-21 concentrations were measured by ELISA. The associations of FGF-21 with glucose, lipids, and insulin were analyzed. Individuals with T1DM showed significantly lower basal FGF-21 concentration (P = 0.046) when compared with healthy controls (median value 28.2 vs 104 pg/mL) and had significantly different postprandial change (∆ 30′−0′) of FGF-21 (P = 0.006) in comparison with healthy controls (median value −1.1 vs −20.5 pg/mL). The glucose and lipid status did not correlate with FGF-21. In healthy controls, postprandial insulin level correlated with basal FGF-21 (ρ = 0.7, P = 0.036). Multiple regression analysis showed that they are independently associated after adjustment for confounding factors (β = 1.824, P = 0.04). We describe the pathological pattern of basal and postprandial change of FGF-21 secretion not associated with glucose, lipid levels, or insulin therapy in patients with T1DM. Since FGF-21 has numerous protective metabolic effects in the experimental model, the lower basal FGF-21 concentration in T1DM patients opens the question about the potential role of recombinant FGF-21 therapy.
KeywordsFibroblast growth factor-21 Type 1 diabetes mellitus C-peptide negative Healthy controls
The authors would like to thank the laboratory staff at Merkur University Hospital, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia. The work was supported by the Ministry of Science, Education and Sports of the Republic of Croatia Grant 045-1080230-0516.
Conflict of interest
The authors declare that there is no conflict of interest.
The study protocol was approved by the Ethics Committee of The University of Zagreb School of Medicine and Merkur University Hospital of Zagreb, Croatia.
- 1.A. Kharitonenkov, T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath, G.E. Sandusky, L.J. Hammond, J.S. Moyers, R.A. Owens, J. Gromada, J.T. Brozinick, E.D. Hawkins, V.J. Wroblewski, D.S. Li, F. Mehrbod, S.R. Jaskunas, A.B. Shanafelt, FGF-21 as a novel metabolic regulator. J. Clin. Investig. 115(6), 1627–1635 (2005)CrossRefPubMedCentralPubMedGoogle Scholar
- 2.M. Mraz, M. Bartlova, Z. Lacinova, D. Michalsky, M. Kasalicky, D. Haluzikova, M. Matoulek, I. Dostalova, V. Humenanska, M. Haluzik, Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin. Endocrinol. 71(3), 369–375 (2009)CrossRefGoogle Scholar
- 4.A.O. Chavez, M. Molina-Carrion, M.A. Abdul-Ghani, F. Folli, R.A. Defronzo, D. Tripathy, 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 32(8), 1542–1546 (2009)CrossRefPubMedCentralPubMedGoogle Scholar
- 6.S.Y. An, M.S. Lee, S.A. Yi, E.S. Ha, S.J. Han, H.J. Kim, D.J. Kim, K.W. Lee, Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques. Diabetes Res. Clin. Pract. 96(2), 196–203 (2012)CrossRefPubMedGoogle Scholar
- 7.F.L. Mashili, R.L. Austin, A.S. Deshmukh, T. Fritz, K. Caidahl, K. Bergdahl, J.R. Zierath, A.V. Chibalin, D.E. Moller, A. Kharitonenkov, A. Krook, Direct effects of FGF21 on glucose uptake in human skeletal muscle: implications for type 2 diabetes and obesity. Diabetes Metab. Res. Rev. 27(3), 286–297 (2011)CrossRefPubMedGoogle Scholar
- 12.A. Kharitonenkov, J.D. Dunbar, H.A. Bina, S. Bright, J.S. Moyers, C. Zhang, L. Ding, R. Micanovic, S.F. Mehrbod, M.D. Knierman, J.E. Hale, T. Coskun, A.B. Shanafelt, FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho. J. Cell. Physiol. 215(1), 1–7 (2008)CrossRefPubMedGoogle Scholar
- 14.T. Uebanso, Y. Taketani, H. Yamamoto, K. Amo, H. Ominami, H. Arai, Y. Takei, M. Masuda, A. Tanimura, N. Harada, H. Yamanaka-Okumura, E. Takeda, Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor? PLoS ONE 6(8), e22976 (2011)CrossRefPubMedCentralPubMedGoogle Scholar
- 17.N. Matikainen, M.-R. Taskinen, S. Stennabb, N. Lundbom, A. Hakkarainen, K. Vaaralahti, T. Raivio, Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat. Eur. J. Endocrinol. 166, 487–492 (2012)CrossRefPubMedGoogle Scholar
- 19.World Health Organization, Department of Noncommunicable Disease Surveillance: Definition, diagnosis and classification of diabetes and its complications. Part 1: diagnosis and classification of diabetes mellitus. World Health Organization, Geneva (1999)Google Scholar
- 22.R.D. Semba, K. Sun, J.M. Egan, C. Crasto, O.D. Carlson, L. Ferrucci, Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: the Baltimore Longitudinal Study of Aging. J. Clin. Endocrinol. Metab. 97(4), 1375–1382 (2012)CrossRefPubMedCentralPubMedGoogle Scholar
- 29.J. Xu, D.J. Lloyd, C. Hale, S. Stanislaus, M. Chen, G. Sivits, S. Vonderfecht, R. Hecht, Y.S. Li, R.A. Lindberg, J.L. Chen, D.Y. Jung, Z. Zhang, H.J. Ko, J.K. Kim, M.M. Veniant, Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58(1), 250–259 (2009)CrossRefPubMedCentralPubMedGoogle Scholar