Abstract
Objectives
Childhood obesity is a serious medical condition with alarmingly high rates worldwide. There is controversy regarding the relationship between insulin-like growth factor-1 (IGF-1) and pediatric obesity. We investigated the relationship between IGF-1, insulin resistance and metabolic profile with childhood pre-obesity/obesity.
Methods
The study involved 201 children aged 7–15 years, divided in three groups according to their nutritional status (International Obesity Task Force criteria): normal-weight (n=84), pre-obese (n=82), obese (n=35). Laboratory IGF-1, insulin, fasting blood glucose (FBG), lipid profile, alanine-aminotransferase (ALT), uric acid (UA), anthropometric and body composition parameters were analyzed. Body mass index and IGF-1 standard deviation score (SDS), waist-to-height ratio (WtHR) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score were calculated.
Results
Pre-obese/obese children had significantly higher IGF-1 SDS, FBG, insulin, HOMA-IR, UA, ALT, triglycerides, and lower high-density lipoprotein cholesterol (HDL-c); obese group had higher WtHR and low-density lipoprotein cholesterol (LDL-c) compared to controls (p<0.05). In obese group, IGF-1 SDS was positively correlated with fat free/muscle mass, total body water (p<0.05) and negatively correlated with LDL-c (p<0.05). In pre-obese/obese HOMA-IR and insulin were positively correlated with age, total body fat (TBF) (p<0.05) and negatively correlated with HDL-c (pre-obese) (p<0.05). Multivariate ordinal logistic regression analyses showed that IGF-1 SDS (OR=1.94; 95%CI: 1.21–3.11), TBF (OR=1.37; 95%CI: 1.21–1.54) were predictors of nutritional status (p<0.001). FBG (OR=42.39; 95%CI: 2.31–77.2) and UA (OR=1.03; 95%CI: 1.01–1.05) were predictors of IR (p<0.001).
Conclusions
IGF-1 SDS and TBF were predictors of nutritional status. Further studies are required to clarify the role of IGF-1 in pathophysiology of obesity and its comorbidities.
Funding source: Ministry of Science, Montenegro
Award Identifier / Grant number: 1366/2012
Research funding: The study was financially supported by the Montenegrin Ministry of Science, Contract No. 1366/2012.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Conception or design: M.J, M.M. Acquisition, analysis, or interpretation of data: M.J., M.M, N.G.B, T.A, M.N.V. Drafting the work or revising: M.J, M.M, M.N.V. Final approval of the manuscript: M.J., M.M, N.G.B, T.A, M.N.V .
Competing interests: Authors state no conflict of interest.
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by Ethics Committee of the Faculty of Medicine, University of Montenegro (Decision No. 3399, 24th of December, 2013).
References
1. Inzaghi, E, Baldini Ferroli, B, Fintini, D, Grossi, A, Nobili, V, Cianfarani, S. Insulin-like growth factors and metabolic syndrome in obese children. Horm Res Paediatr 2017;87:400–4. https://doi.org/10.1159/000477241.Search in Google Scholar
2. Lewitt, MS, Dent, MS, Hall, K. The insulin-like growth factor system in obesity, insulin resistance and type 2 diabetes mellitus. J Clin Med 2014;3:1561–74. https://doi.org/10.3390/jcm3041561.Search in Google Scholar
3. Liang, S, Hu, Y, Liu, C, Qi, J, Li, G. Low insulin-like growth factor 1 is associated with low high-density lipoprotein cholesterol and metabolic syndrome in Chinese nondiabetic obese children and adolescents: a cross-sectional study. Lipids Health Dis 2016;15:112. https://doi.org/10.1186/s12944-016-0275-7.Search in Google Scholar
4. Aguirre, GA, De Ita, JR, de la Garza, RG, Castilla-Cortazar, I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med 2016;14:3. https://doi.org/10.1186/s12967-015-0762-z.Search in Google Scholar
5. Hawkes, CP, Grimberg, A. Insulin-like growth factor-I is a marker for the nutritional state. Pediatr Endocrinol Rev 2015;13:499–511.Search in Google Scholar
6. Xie, S, Jiang, R, Xu, W, Chen, Y, Tang, L, Li, L, et al.. The relationship between serum-free insulin-like growth factor-1 and metabolic syndrome in school adolescents of northeast China. Diabetes Metab Syndr Obes 2019;12:305–13. https://doi.org/10.2147/dmso.s195625.Search in Google Scholar
7. Friedrich, N, Thuesen, B, Jørgensen, T, Juul, A, Spielhagen, C, Wallaschofksi, H, et al.. The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care 2012;35:768–73. https://doi.org/10.2337/dc11-1833.Search in Google Scholar
8. Rajpathak, SN, Gunter, MJ, Wylie-Rosett, J, Ho, GY, Kaplan, RC, Muzumdar, R, et al.. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev 2009;25:3–12. https://doi.org/10.1002/dmrr.919.Search in Google Scholar
9. Levy-Marchal, C, Arslanian, S, Cutfield, W, Sinaiko, A, Druet, C, Marcovecchio, ML, et al.. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metabol 2010;95:5189–98. https://doi.org/10.1210/jc.2010-1047.Search in Google Scholar
10. Tagi, VM, Giannini, C, Chiarelli, F. Insulin resistance in children. Front Endocrinol 2019;10:342. https://doi.org/10.3389/fendo.2019.00342.Search in Google Scholar
11. Kurtoğlu, S, Hatipoğlu, N, Mazıcıoğlu, M, Kendirici, M, Keskin, M, Kondolot, M. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol 2010;2:100–6.10.4274/jcrpe.v2i3.100Search in Google Scholar PubMed PubMed Central
12. Kim, ES, Park, JH, Lee, MK, Lee, DH, Kang, ES, Lee, HC, et al.. Associations between fatness, fitness, IGF and IMT among obese Korean male adolescents. Diabetes Metab J 2011;35:610–18. https://doi.org/10.4093/dmj.2011.35.6.610.Search in Google Scholar
13. Marseglia, L, Manti, S, D’Angelo, G, Nicotera, A, Parisi, E, Di Rosa, G, et al.. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 2014;16:378–400. https://doi.org/10.3390/ijms16010378.Search in Google Scholar
14. Madsen, AL, Larnkjær, A, Mølgaard, C, Michaelsen, KF. IGF-I and IGFBP-3 in healthy 9 month old infants from the SKOT cohort: breastfeeding, diet, and later obesity. Horm IGF Res 2011;21:199–204. https://doi.org/10.1016/j.ghir.2011.05.003.Search in Google Scholar
15. Puche, JE, Castilla-Cortázar, I. Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J Transl Med 2012;10:224. https://doi.org/10.1186/1479-5876-10-224.Search in Google Scholar
16. Cirrik, S, Schmid-Schönbein, GW. IGF-1 receptor cleavage in hypertension. Hypertens Res 2018;41:406–13. https://doi.org/10.1038/s41440-018-0023-7.Search in Google Scholar
17. Schutte, AE, Volpe, M, Tocci, G, Conti, E. Revisiting the relationship between blood pressure and insulin-like growth factor-1. Hypertension 2014;63:1070–7. https://doi.org/10.1161/hypertensionaha.113.03057.Search in Google Scholar
18. Eyzaguirre, F, Mericq, V. Insulin resistance markers in children. Horm Res 2009;71:65–74. https://doi.org/10.1159/000183894.Search in Google Scholar
19. Zhu, Y, Hu, Y, Huang, T, Zhang, Y, Li, Z, Luo, C, et al.. High uric acid directly inhibits insulin signalling and induces insulin resistance. Biochem Biophys Res Commun 2014;447:707–14. https://doi.org/10.1016/j.bbrc.2014.04.080.Search in Google Scholar
20. Yadav, D, Lee, ES, Kim, HM, Lee, EY, Choi, E, Chung, CH. Hyperuricemia as a potential determinant of metabolic syndrome. J Lifestyle Med 2013;3:98–106.Search in Google Scholar
21. Liang, S, Zhang, D, Qi, J, Song, X, Xue, J. Reduced peak stimulated growth hormone is associated with hyperuricemia in obese children and adolescents. Sci Rep 2018;8:7931. https://doi.org/10.1038/s41598-018-26276-w.Search in Google Scholar
22. Martinovic, M, Belojevic, G, Evans, GW, Lausevic, D, Asanin, B, Samardzic, M, et al.. Prevalence of and contributing factors for overweight and obesity among Montenegrin schoolchildren. Eur J Pub Health 2015:833–9. https://doi.org/10.1093/eurpub/ckv071.Search in Google Scholar
23. Cole, TJ, Lobstein, T. Extended international BMI cut‐offs. Pediatr Obes 2012:284–94. https://doi.org/10.1111/j.2047-6310.2012.00064.x.Search in Google Scholar
24. Todendi, PF, Possuelo, LG, Klinger, EI, Reuter, CP, Burgos, MS, Moura, DJ, et al.. Low-grade inflammation markers in children and adolescents: influence of anthropometric characteristics and CRP and IL6 polymorphisms. Cytokine 2016;88:177–83. https://doi.org/10.1016/j.cyto.2016.09.007.Search in Google Scholar
25. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303. https://doi.org/10.1136/adc.44.235.291.Search in Google Scholar
26. van der Aa, MP, Knibbe, CA, Boer, A, van der Vorst, MM. Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus. J Pediatr Endocrinol Metab 2017;30:123–31. https://doi.org/10.1515/jpem-2016-0242.Search in Google Scholar
27. Ricco, RC, Ricco, RG, Queluz, MC, de Paula, MT, Atique, PV, Custódio, RJ, et al.. IGF-1R mRNA expression is increased in obese children. Growth Horm IGF Res 2018;39:1–5. https://doi.org/10.1016/j.ghir.2017.11.001.Search in Google Scholar
28. Sirbu, A. IGF-I deficiency among obese women linked to adiponectin, BMI, ALT, steatosis. Growth Horm IGF Res 2013;23:2–7. https://doi.org/10.1016/j.ghir.2012.10.001.Search in Google Scholar
29. AsghariHanjani, N, Vafa, M. The role of IGF-1 in obesity, cardiovascular disease, and cancer. Med J Islam Repub Iran 2019;17:56.10.47176/mjiri.33.56Search in Google Scholar
30. Haywood, NJ, Slater, TA, Matthews, CJ, Wheatcroft, SB. The insulin like growth factor and binding protein family: novel therapeutic targets in obesity & diabetes. Mol Metab 2019;19:86–96. https://doi.org/10.1016/j.molmet.2018.10.008.Search in Google Scholar
31. Berryman, DE, Glad, CAM, List, EO, Johannsson, G. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. Nat Rev Endocrinol 2013:346–56. https://doi.org/10.1038/nrendo.2013.64.Search in Google Scholar
32. El-Maghraby, AE, Aissa, EA, El, H, Ahmed, H. Estimation of insulin-like growth factor-1 as a biomarker in nonalcoholic fatty liver disease in patients with metabolic syndrome. J Med Sci Res 2018;1:73–8. https://doi.org/10.4103/jmisr.jmisr_26_18.Search in Google Scholar
33. Sesti, G, Hribal, ML, Procopio, T, Fiorentino, TV, Sciacqua, A, Andreozzi, F, et al.. Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects. Nutr Metab Cardiovasc Dis 2014:1365–72. https://doi.org/10.1016/j.numecd.2014.06.012.Search in Google Scholar
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