Subscribe to RSS
DOI: 10.1055/a-1937-1155
Clinical Value of Serum BMP-4, BMP-2, GDF-15, MMP-9, GP39 Levels in Pregnant Women with Obesity and the Related Comorbidities Diabetes Mellitus and Gestational Hypertension
Abstract
Aims We evaluated the clinical value of selected serum biomarkers BMP-4, BMP-2, GDF-15, MMP-9, and GP39 in pregnant women with obesity and the comorbidities diabetes mellitus (DM) and gestational hypertension (GHT).
Methods This observational study had groups of controls, including healthy pregnant women; women with only obesity, including pregnant women with BMI≥30 kg/m2; women with gestational DM (GDM) with obesity, including pregnant women with GDM and obesity; women with pregestational DM (PGDM) with obesity, including pregnant women with PGDM and obesity; and women with GHT with obesity, including pregnant women with GHT and obesity. We measured serum levels of selected biomarkers by ELISA.
ResultsObesity increased serum levels of all the biomarkers; GDM developed in obese women caused a more pronounced increase in the serum levels of BMP-4 and BMP-2, and GHT developed in obese women caused a more pronounced increase in the serum levels of GDF-15. In the women with GDM-, PGDM-, and GHT-complicated obesity, serum levels of MMP-9 and GP39 did not change meaningfully.
Conclusions Obesity and its comorbidities DM and GHT lead to meaningful changes in the studied serum biomarkers. Since obesity has a causal effect on developing numerous conditions, reliable clinical biomarkers are needed to improve the early prediction and diagnosis of high-risk conditions during pregnancy.
Publication History
Received: 29 March 2022
Accepted after revision: 16 August 2022
Article published online:
28 September 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Marchi J, Berg M, Dencker A. et al. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews. Obes Rev an Off J Int Assoc Study Obes 2015; 16: 621-638 DOI: 10.1111/obr.12288.
- 2 Fakhraei R, Denize K, Simon A. et al. Predictors of adverse pregnancy outcomes in pregnant women living with obesity: a systematic review. Int J Environ Res Public Health 2022; 19: 2063 DOI: 10.3390/ijerph19042063.
- 3 Egan AM, Dennedy MC, Al-Ramli W. et al. ATLANTIC-DIP: excessive gestational weight gain and pregnancy outcomes in women with gestational or pregestational diabetes mellitus. J Clin Endocrinol Metab 2014; 99: 212-219 DOI: 10.1210/jc.2013-2684.
- 4 Fernández Alba JJ, Mesa Páez C, Vilar Sánchez Á. et al. [Overweight and obesity at risk factors for hypertensive states of pregnancy: a retrospective cohort study]. Nutr Hosp 2018; 35: 874-880 DOI: 10.20960/nh.1702.
- 5 Sagi-Dain L.. Obesity in Pregnancy: ACOG Practice Bulletin, Number 230. Obstet Gynecol 2021; 138: 489 DOI: 10.1097/AOG.0000000000004527.
- 6 Catalano PM, Shankar K.. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ 2017; 356: j1 DOI: 10.1136/bmj.j1.
- 7 Longo M, Zatterale F, Naderi J. et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci 2019; 20: 2358 DOI: 10.3390/ijms20092358.
- 8 Lee M-W, Lee M, Oh K-J.. Adipose tissue-derived signatures for obesity and type 2 diabetes: adipokines, batokines and microRNAs. J Clin Med 2019; 8: 854 DOI: 10.3390/jcm8060854.
- 9 Smith U, Kahn BB.. Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J Intern Med 2016; 280: 465-475 DOI: 10.1111/joim.12540.
- 10 Kazemian E, Sotoudeh G, Dorosty-Motlagh AR. et al. Maternal obesity and energy intake as risk factors of pregnancy-induced hypertension among Iranian women. J Health Popul Nutr 2014; 32: 486-493
- 11 Santos S, Voerman E, Amiano P. et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts. BJOG 2019; 126: 984-995 DOI: 10.1111/1471-0528.15661.
- 12 Sun Y, Shen Z, Zhan Y. et al. Effects of pre-pregnancy body mass index and gestational weight gain on maternal and infant complications. BMC Pregnancy Childbirth 2020; 20: 390 DOI: 10.1186/s12884-020-03071-y.
- 13 Choe SS, Huh JY, Hwang IJ. et al. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne) 2016; 7: 30 DOI: 10.3389/fendo.2016.00030.
- 14 Huh JY, Park YJ, Ham M. et al. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells 2014; 37: 365-371 DOI: 10.14348/molcells.2014.0074.
- 15 Wu H, Ballantyne CM.. Metabolic inflammation and insulin resistance in obesity. Circ Res 2020; 126: 1549-1564 DOI: 10.1161/CIRCRESAHA.119.315896.
- 16 Leitner DR, Frühbeck G, Yumuk V. et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts 2017; 10: 483-492 DOI: 10.1159/000480525.
- 17 Baboota R, Blüher M, Smith U.. Emerging role of bone morphogenetic protein 4 in metabolic disorders. Diabetes 2021; 70: 303-312 DOI: 10.2337/db20-0884.
- 18 Kim JY, Lim S, Lim H-S. et al. Bone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 2021; 148: 461-472.e13 DOI: 10.1016/j.jaci.2021.02.027.
- 19 Wischhusen J, Melero I, Fridman WH.. Growth/differentiation factor-15 (GDF-15): from biomarker to novel targetable immune checkpoint. Front Immunol 2020; 11: 951 DOI: 10.3389/fimmu.2020.00951.
- 20 Sarkar S, Melchior JT, Henry HR. et al. GDF15: a potential therapeutic target for type 1 diabetes. Expert Opin Ther Targets 2022; 26: 57-67 DOI: 10.1080/14728222.2022.2029410.
- 21 Unal R, Yao-Borengasser A, Varma V. et al. Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone. J Clin Endocrinol Metab 2010; 95: 2993-3001 DOI: 10.1210/jc.2009-2623.
- 22 Rathcke CN, Vestergaard H.. YKL-40--an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol 2009; 8: 61 DOI: 10.1186/1475-2840-8-61.
- 23 Thomsen SB, Gjesing AP, Rathcke CN. et al. Associations of the inflammatory marker YKL-40 with measures of obesity and dyslipidaemia in individuals at high risk of type 2 diabetes. PLoS One 2015; 10: e0133672 DOI: 10.1371/journal.pone.0133672.
- 24 Coustan DR, Lowe LP, Metzger BE. et al. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol 2010; 202: e1-e6 DOI: 10.1016/j.ajog.2010.04.006.
- 25 Newman C, Egan AM, Ahern T. et al. Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland. Diabetes Res Clin Pract 2021; 173: 108685 DOI: 10.1016/j.diabres.2021.108685.
- 26 Cordero L, Stenger MR, Landon MB. et al. Exclusive breastfeeding among women with type 1 and type 2 diabetes mellitus. BMC Pregnancy Childbirth 2022; 22: 69 DOI: 10.1186/s12884-022-04411-w.
- 27 Brown MA, Magee LA, Kenny LC. et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertens (Dallas, Tex 1979) 2018; 72: 24-43 DOI: 10.1161/HYPERTENSIONAHA.117.10803.
- 28 Tanner MS, Malhotra A, Davey M-A. et al. Maternal and neonatal complications in women with medical comorbidities and preeclampsia. Pregnancy Hypertens 2022; 27: 62-68 DOI: 10.1016/j.preghy.2021.12.006.
- 29 Alfadhli EM.. Maternal obesity influences birth weight more than gestational diabetes. BMC Pregnancy Childbirth 2021; 21: 111 DOI: 10.1186/s12884-021-03571-5.
- 30 Barbour LA, McCurdy CE, Hernandez TL. et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 2007; 30: S112-S119 DOI: 10.2337/dc07-s202.
- 31 Bozkurt L, Göbl CS, Pfligl L. et al. Pathophysiological characteristics and effects of obesity in women with early and late manifestation of gestational diabetes diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. J Clin Endocrinol Metab 2015; 100: 1113-1120 DOI: 10.1210/jc.2014-4055.
- 32 Saudan P, Brown MA, Buddle ML. et al. Does gestational hypertension become pre-eclampsia?. Br J Obstet Gynaecol 1998; 105: 1177-1184 DOI: 10.1111/j.1471-0528.1998.tb09971.x.
- 33 Son J-W, Kim M-K, Park Y-M. et al. Association of serum bone morphogenetic protein 4 levels with obesity and metabolic syndrome in non-diabetic individuals. Endocr J 2011; 58: 39-46 DOI: 10.1507/endocrj.k10e-248.
- 34 Cai B, Du J.. Role of bone morphogenic protein-4 in gestational diabetes mellitus-related hypertension. Exp Ther Med 2021; 22: 762 DOI: 10.3892/etm.2021.10194.
- 35 Kim MK, Jang E-H, Hong O-K. et al. Changes in serum levels of bone morphogenic protein 4 and inflammatory cytokines after bariatric surgery in severely obese Korean patients with type 2 diabetes. Int J Endocrinol 2013; 2013: 681205 DOI: 10.1155/2013/681205.
- 36 Luna-Luna M, Criales-Vera S, Medina-Leyte D. et al. Bone morphogenetic protein-2 and osteopontin gene expression in epicardial adipose tissue from patients with coronary artery disease is associated with the presence of calcified atherosclerotic plaques. Diabetes Metab Syndr Obes 2020; 13: 1943-1951 DOI: 10.2147/DMSO.S253632.
- 37 Guiu-Jurado E, Unthan M, Böhler N. et al. Bone morphogenetic protein 2 (BMP2) may contribute to partition of energy storage into visceral and subcutaneous fat depots. Obesity (Silver Spring) 2016; 24: 2092-2100 DOI: 10.1002/oby.21571.
- 38 Dostálová I, Roubícek T, Bártlová M. et al. Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet. Eur J Endocrinol 2009; 161: 397-404 DOI: 10.1530/EJE-09-0417.
- 39 Vila G, Riedl M, Anderwald C. et al. The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients. Clin Chem 2011; 57: 309-316 DOI: 10.1373/clinchem.2010.153726.
- 40 Tang M, Luo M, Lu W. et al. Serum growth differentiation factor 15 is associated with glucose metabolism in the third trimester in Chinese pregnant women. Diabetes Res Clin Pract 2019; 156: 107823 DOI: 10.1016/j.diabres.2019.107823.
- 41 Andersson-Hall U, Joelsson L, Svedin P. et al. Growth-differentiation-factor 15 levels in obese and healthy pregnancies: relation to insulin resistance and insulin secretory function. Clin Endocrinol (Oxf) 2021; 95: 92-100 DOI: 10.1111/cen.14433.
- 42 Derosa G, Ferrari I, D’Angelo A. et al. Matrix metalloproteinase-2 and -9 levels in obese patients. Endothelium 2008; 15: 219-224 DOI: 10.1080/10623320802228815.
- 43 Palei ACT, Sandrim VC, Cavalli RC. et al. Comparative assessment of matrix metalloproteinase (MMP)-2 and MMP-9, and their inhibitors, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in preeclampsia and gestational hypertension. Clin Biochem 2008; 41: 875-880 DOI: 10.1016/j.clinbiochem.2008.04.015.
- 44 Boumiza S, Chahed K, Tabka Z. et al. MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity. Sci Rep 2021; 11: 20052 DOI: 10.1038/s41598-021-99577-2.
- 45 Maquoi E, Munaut C, Colige A. et al. Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes 2002; 51: 1093-1101 DOI: 10.2337/diabetes.51.4.1093.
- 46 Timokhina E, Zinin V, Ignatko I. et al. Matrix metalloproteinases MMP-2 and MMP-9 as markers for the prediction of preeclampsia in the first trimester. Ces Gynekol 2021; 86: 228-235 DOI: 10.48095/cccg2021228.
- 47 Hempen M, Kopp H-P, Elhenicky M. et al. YKL-40 is elevated in morbidly obese patients and declines after weight loss. Obes Surg 2009; 19: 1557-1563 DOI: 10.1007/s11695-009-9917-4.
- 48 Yi Z, Bishop GA.. Regulatory role of CD40 in obesity-induced insulin resistance. Adipocyte 2015; 4: 65-69 DOI: 10.4161/adip.32214.