Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus.
FGF23
birth cohort study
cFGF23
gestational diabetes mellitus
iFGF23
Journal
Diabetes/metabolism research and reviews
ISSN: 1520-7560
Titre abrégé: Diabetes Metab Res Rev
Pays: England
ID NLM: 100883450
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
01
07
2023
received:
02
05
2023
accepted:
12
07
2023
medline:
3
11
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
Besides its established impact on bone and mineral metabolism, it was suggested that fibroblast growth factor 23 (FGF23) might play an important role in the pathogenesis of type 2 diabetes. The impact of FGF23 on gestational diabetes mellitus (GDM), however, is not well understood. iFGF23 ELISAs measure the intact FGF23 molecule, whereas cFGF23 assays measure intact FGF23 as well as degradation products of FGF23. The aim of this study is to compare the association of maternal and foetal cFGF23 and iFGF23 with GDM in a German birth cohort. cFGF23 and iFGF23 were analysed in 826 random mother/child pairs from the Berlin Birth Cohort. Mothers who developed GDM had higher concentrations of iFGF-23 compared to mothers who did not suffer from GDM (19.73 vs. 13.23 pg/mL, p < 0.0001), but not higher concentrations of cFGF-23. Multivariant regression analyses showed that gestational diabetes is associated with iFGF23 independently of confounding factors such as age, BMI, ethnic background, family history of diabetes, smoking during pregnancy, and recurrent pregnancy loss. This, however, was only seen when using an iFGF23 ELISA measuring just the full length FGF23 and not in addition FGF23 fragments. No differences in both iFGF23 and cFGF23 concentrations between the GDM and non-GDM groups were detected in cord blood samples of the offspring. This study of a representative German birth cohort showed that maternal but not foetal iFGF23 is independently associated with GDM.
Sections du résumé
BACKGROUND
Besides its established impact on bone and mineral metabolism, it was suggested that fibroblast growth factor 23 (FGF23) might play an important role in the pathogenesis of type 2 diabetes. The impact of FGF23 on gestational diabetes mellitus (GDM), however, is not well understood. iFGF23 ELISAs measure the intact FGF23 molecule, whereas cFGF23 assays measure intact FGF23 as well as degradation products of FGF23.
OBJECTIVES
The aim of this study is to compare the association of maternal and foetal cFGF23 and iFGF23 with GDM in a German birth cohort.
METHODS
cFGF23 and iFGF23 were analysed in 826 random mother/child pairs from the Berlin Birth Cohort.
RESULTS
Mothers who developed GDM had higher concentrations of iFGF-23 compared to mothers who did not suffer from GDM (19.73 vs. 13.23 pg/mL, p < 0.0001), but not higher concentrations of cFGF-23. Multivariant regression analyses showed that gestational diabetes is associated with iFGF23 independently of confounding factors such as age, BMI, ethnic background, family history of diabetes, smoking during pregnancy, and recurrent pregnancy loss. This, however, was only seen when using an iFGF23 ELISA measuring just the full length FGF23 and not in addition FGF23 fragments. No differences in both iFGF23 and cFGF23 concentrations between the GDM and non-GDM groups were detected in cord blood samples of the offspring.
CONCLUSIONS
This study of a representative German birth cohort showed that maternal but not foetal iFGF23 is independently associated with GDM.
Substances chimiques
Fibroblast Growth Factor-23
7Q7P4S7RRE
Fibroblast Growth Factors
62031-54-3
FGF23 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3704Informations de copyright
© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.
Références
Rausch S, Foller M. The regulation of FGF23 under physiological and pathophysiological conditions. Pflugers Arch. 2022;474(3):281-292. https://doi.org/10.1007/s00424-022-02668-w
Bar L, Stournaras C, Lang F, Foller M. Regulation of fibroblast growth factor 23 (FGF23) in health and disease. FEBS Lett. 2019;593(15):1879-1900. https://doi.org/10.1002/1873-3468.13494
Lang F, Leibrock C, Pandyra AA, Stournaras C, Wagner CA, Foller M. Phosphate homeostasis, inflammation and the regulation of FGF-23. Kidney Blood Press Res. 2018;43(6):1742-1748. https://doi.org/10.1159/000495393
Donate-Correa J, Martin-Nunez E, Gonzalez-Luis A, et al. Pathophysiological implications of imbalances in fibroblast growth factor 23 in the development of diabetes. J Clin Med. 2021;10(12):2583. https://doi.org/10.3390/jcm10122583
Mirza MA, Alsio J, Hammarstedt A, et al. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol. 2011;31(1):219-227. https://doi.org/10.1161/atvbaha.110.214619
Wojcik M, Dolezal-Oltarzewska K, Janus D, Drozdz D, Sztefko K, Starzyk JB. FGF23 contributes to insulin sensitivity in obese adolescents - preliminary results. Clin Endocrinol. 2012;77(4):537-540. https://doi.org/10.1111/j.1365-2265.2011.04299.x
Garland JS, Holden RM, Ross R, et al. Insulin resistance is associated with fibroblast growth factor-23 in stage 3-5 chronic kidney disease patients. J Diabetes Complicat. 2014;28(1):61-65. https://doi.org/10.1016/j.jdiacomp.2013.09.004
Hanks LJ, Casazza K, Judd SE, Jenny NS, Gutierrez OM. Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults. PLoS One. 2015;10(3):e0122885. https://doi.org/10.1371/journal.pone.0122885
Vervloet MG, van Zuilen AD, Heijboer AC, et al. Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: an analysis of the MASTERPLAN cohort. BMC Nephrol. 2012;13(1):20. https://doi.org/10.1186/1471-2369-13-20
Schoppet M, Hofbauer LC, Brinskelle-Schmal N, et al. Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. J Clin Endocrinol Metab. 2012;97(4):E575-E583. https://doi.org/10.1210/jc.2011-2836
Hu X, Ma X, Luo Y, et al. Elevation in fibroblast growth factor 23 and its value for identifying subclinical atherosclerosis in first-degree relatives of patients with diabetes. Sci Rep. 2016;6(1):34696. https://doi.org/10.1038/srep34696
Wahl P, Xie H, Scialla J, et al. Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease. Diabetes Care. 2012;35(5):994-1001. https://doi.org/10.2337/dc11-2235
Donate-Correa J, Martin-Nunez E, Hernandez-Carballo C, et al. Fibroblast growth factor 23 expression in human calcified vascular tissues. Aging. 2019;11(18):7899-7913. https://doi.org/10.18632/aging.102297
Gateva A, Assyov Y, Tsakova A, Kamenov Z. Prediabetes is characterized by higher FGF23 levels and higher prevalence of vitamin D deficiency compared to normal glucose tolerance subjects. Horm Metab Res. 2019;51(2):106-111. https://doi.org/10.1055/a-0813-3164
Fernandez-Real JM, Puig J, Serrano M, et al. Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations. PLoS One. 2013;8(3):e58961. https://doi.org/10.1371/journal.pone.0058961
Bar L, Feger M, Fajol A, et al. Insulin suppresses the production of fibroblast growth factor 23 (FGF23). Proc Natl Acad Sci U S A. 2018;115(22):5804-5809. https://doi.org/10.1073/pnas.1800160115
Hocher B, Slowinski T, Stolze T, Pleschka A, Neumayer HH, Halle H. Association of maternal G protein beta3 subunit 825T allele with low birthweight. Lancet. 2000;355(9211):1241-1242. https://doi.org/10.1016/s0140-6736(00)02094-8
Pfab T, Slowinski T, Godes M, Halle H, Priem F, Hocher B. Low birth weight, a risk factor for cardiovascular diseases in later life, is already associated with elevated fetal glycosylated hemoglobin at birth. Circulation. 2006;114(16):1687-1692. https://doi.org/10.1161/circulationaha.106.625848
Nair AV, Hocher B, Verkaart S, et al. Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy. Proc Natl Acad Sci U S A. 2012;109(28):11324-11329. https://doi.org/10.1073/pnas.1113811109
Putra SED, Reichetzeder C, von Websky K, et al. Association between placental global DNA methylation and blood pressure during human pregnancy. J Hypertens. 2022;40(5):1002-1009. https://doi.org/10.1097/hjh.0000000000003103
Tsuprykov O, Elitok S, Buse C, Chu C, Kramer BK, Hocher B. Opposite correlation of 25-hydroxy-vitamin D- and 1,25-dihydroxy-vitamin D-metabolites with gestational age, bone- and lipid-biomarkers in pregnant women. Sci Rep. 2021;11(1):1923. https://doi.org/10.1038/s41598-021-81452-9
Dwi Putra SE, Reichetzeder C, Hasan AA, et al. Being born large for gestational age is associated with increased global placental DNA methylation. Sci Rep. 2020;10(1):927. https://doi.org/10.1038/s41598-020-57725-0
Lu YP, Reichetzeder C, Prehn C, et al. Fetal serum metabolites are independently associated with gestational diabetes mellitus. Cell Physiol Biochem. 2018;45(2):625-638. https://doi.org/10.1159/000487119
Warrington NM, Beaumont RN, Horikoshi M, et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet. 2019;51(5):804-814. https://doi.org/10.1038/s41588-019-0403-1
Chu C, Elitok S, Zeng S, et al. C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. BMC Nephrol. 2021;22(1):125. https://doi.org/10.1186/s12882-021-02329-7
Enlund-Cerullo M, Hauta-Alus H, Valkama S, et al. Fibroblast growth factor 23 concentrations and modifying factors in children from age 12 to 24 months. Bone. 2020;141:115629. https://doi.org/10.1016/j.bone.2020.115629
Leaf DE, Siew ED, Eisenga MF, et al. Fibroblast growth factor 23 associates with death in critically ill patients. Clin J Am Soc Nephrol. 2018;13(4):531-541. https://doi.org/10.2215/cjn.10810917
Kleinwechter H, Schafer-Graf U, Buhrer C, et al. Gestational diabetes mellitus (GDM) diagnosis, therapy and follow-up care: practice guideline of the German diabetes association(DDG) and the German association for gynaecologyand obstetrics (DGGG). Exp Clin Endocrinol Diabetes. 2014;122(7):395-405. https://doi.org/10.1055/s-0034-1366412
Kharitonenkov A. FGFs and metabolism. Curr Opin Pharmacol. 2009;9(6):805-810. https://doi.org/10.1016/j.coph.2009.07.001
Nakashima A, Yokoyama K, Kawanami D, et al. Association between resistin and fibroblast growth factor 23 in patients with type 2 diabetes mellitus. Sci Rep. 2018;8(1):13999. https://doi.org/10.1038/s41598-018-32432-z
Yeung SMH, Bakker SJL, Laverman GD, De Borst MH. Fibroblast growth factor 23 and adverse clinical outcomes in type 2 diabetes: a bitter-sweet symphony. Curr Diab Rep. 2020;20(10):50. https://doi.org/10.1007/s11892-020-01335-7
Kizilgul M, Kan S, Beysel S, et al. Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes? Arch Endocrinol Metab. 2017;61(6):562-566. https://doi.org/10.1590/2359-3997000000287
Tuzun D, Oguz A, Aydin MN, et al. Is FGF-23 an early indicator of atherosclerosis and cardiac dysfunction in patients with gestational diabetes? Arch Endocrinol Metab. 2018;62(5):506-513. https://doi.org/10.20945/2359-3997000000070
Mosavat M, Omar SZ, Sthanshewar P. Serum FGF-21 and FGF-23 in association with gestational diabetes: a longitudinal case-control study. Horm Mol Biol Clin Investig. 2020;41(2). https://doi.org/10.1515/hmbci-2019-0060
Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens. 2014;23(4):411-419. https://doi.org/10.1097/01.mnh.0000447020.74593.6f
Jonsson KB, Zahradnik R, Larsson T, et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003;348(17):1656-1663. https://doi.org/10.1056/nejmoa020881
Ratsma DMA, Zillikens MC, van der Eerden BCJ. Upstream regulators of fibroblast growth factor 23. Front Endocrinol. 2021;12:588096.
Garbe C, McLeod GR, Buettner PG. Time trends of cutaneous melanoma in Queensland, Australia and central Europe. Cancer. 2000;89(6):1269-1278. https://doi.org/10.1002/1097-0142(20000915)89:6<1269::aid-cncr11>3.0.co;2-c
Mareckova K, Klasnja A, Andryskova L, Brazdil M, Paus T. Developmental origins of depression-related white matter properties: findings from a prenatal birth cohort. Hum Brain Mapp. 2019;40(4):1155-1163. https://doi.org/10.1002/hbm.24435
McBride D, Keil T, Grabenhenrich L, et al. The EuroPrevall birth cohort study on food allergy: baseline characteristics of 12,000 newborns and their families from nine European countries. Pediatr Allergy Immunol. 2012;23(3):230-239. https://doi.org/10.1111/j.1399-3038.2011.01254.x
Winther K, Nybo M, Vind B, Pedersen SM, Hojlund K, Rasmussen LM. Acute hyperinsulinemia is followed by increased serum concentrations of fibroblast growth factor 23 in type 2 diabetes patients. Scand J Clin Lab Invest. 2012;72(2):108-113. https://doi.org/10.3109/00365513.2011.640407
Hocher B, Schlemm L, Haumann H, et al. Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy. J Renin Angiotensin Aldosterone Syst. 2011;12(3):254-261. https://doi.org/10.1177/1470320310387843
Hocher B, Schlemm L, Haumann H, et al. Interaction of maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala polymorphism with fetal sex affects maternal glycemic control during pregnancy. Pharmacogenet Genomics. 2010;20(2):139-142. https://doi.org/10.1097/fpc.0b013e3283357337
Chen H, Li J, Cai S, et al. Blastocyst transfer: a risk factor for gestational diabetes mellitus in women undergoing in vitro fertilization. J Clin Endocrinol Metab. 2022;107(1):e143-e152. https://doi.org/10.1210/clinem/dgab594