Evaluation of metabolic factors affecting the presence of hepatosteatosis and the effect of insulin like growth factor-1 level in overweight and obese children
Abstract views: 120 / PDF downloads: 96
Keywords:Children, insulin like growth factor-1, non-alcholic fatty liver disease, overweight
Although previous studies related to non-alcoholic fatty liver disease (NAFLD) in childhood were predominantly ALT and uric acid level, the number of studies that have been handled in terms of insulin like growth factor-1 (IGF-1) level or IGF-1 standard deviation score (SDS) is limited. In this study, all factors that may affect NAFLD, including IGF-1 level and IGF-1 SDS, were evaluated in two groups of children who were not statistically different from each other in terms of age, gender, weight, height, body mass index and puberty. This study was a cross sectional study. 36 children with evidence of fatty liver disease on ultrasound imaging and 38 children without it were included in the study. Anthropometric data, laboratory measurements and radiological results of all participants were evaluated. All factors that could affect NAFLD were evaluated by binary logistic regression analysis. Weight, weight SDS, body mass index (BMI) SDS, homeostasis model assessment of insulin resistance (HOMA-IR), AST, ALT, GGT, uric acid, triglyceride, HDLcholesterol, IGF-1, IGF-1 SDS were evaluated in this model to predict NAFLD. In the statistical model, the percentage of predicting those with NAFLD, that is, the sensitivity, was 88.9%, while the detection rate of those without NAFLD, that is, the specificity, was 94.7%. IGF-1 level was found to be significantly lower in the group with NAFLD (p: 0.04), but there was no significant difference between the groups in terms of IGF-1 SDS (p: 0.10). There are conflicting results in studies examining the relationship between IGF-1 SDS and NAFLD. This may be due to ethnicity, regional differences, kit-specific laboratory reference ranges, or method of measurement. Laboratory measurements including appropriate parameters with a detailed physical examination can be used to predict the presence of NAFLD without the need for radiological examination.
Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388-93. doi: 10.1542/peds.2006-1212.
Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: A systematic review and meta-analysis. PLoS ONE. 2015:10(10):0140908. doi: 10.1371/journal.pone.0140908.
Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol. 2011;17(26):3082-91. doi: 10.3748/wjg.v17.i26.3082.
Giorgio V, Prono F, Graziano F, Nobili V. Pediatric non alcoholic fatty liver disease: Old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr. 2013;13:40. doi: 10.1186/1471-2431-13-40.
Jimenez-Rivera C, Hadjiyannakis S, Davila J, Hurteau J, Aglipay M, Barrowman N, et al. Prevalence and risk factors for non-alcoholic fatty liver in children and youth with obesity. BMC Pediatr. 2017;17(1):113. doi: 10.1186/s12887-017-0867-z.
Liang S, Cheng X, Hu Y, Song R, Li G. Insulin-like growth factor 1 and metabolic parameters are associated with nonalcoholic fatty liver disease in obese children and adolescents. Acta Paediatr. 2017;106(2):298-303. doi: 10.1111/apa.13685.
Hribal ML, Procopio T, Petta S, Sciacqua A, Grimaudo S, Pipitone RM, et al. Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2013;98(2):304-8. doi: 10.1210/jc.2012-3290.
Sumida Y, Yonei Y, Tanaka S, Mori K, Kanemasa K, Imai S, et al. Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease. Hepatol Res. 2015;45(7):771-81. doi: 10.1111/hepr.12408.
Cianfarani S, Inzaghi E, Alisi A, Germani D, Puglianiello A, Nobili V. Insulin-like growth factor-I and -II levels are associated with the progression of nonalcoholic fatty liver disease in obese children. J Pediatr. 2014;165(1):92-8. doi: 10.1016/j.jpeds.2014.01.052.
Garcia-Galiano D, Sanchez-Garrido MA, Espejo I, Montero JL, Costan G, Marchal T, et al. IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2007;17(4):493-503. doi: 10.1007/s11695-007-9087-1.
Demir K, Ozen S, Konakci E, Aydin M, Darendeliler F. A comprehensive online calculator for pediatric endocrinologists: CEDD Cozum/TPEDS Metrics. J Clin Res Pediatr Endocrinol. 2017; 9(2):182-4. doi: 10.4274/jcrpe.4526.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. doi: 10.1007/BF00280883.
Guven B, Can M, Mungan G, Acikgoz S. Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest. 2013;73(2):135-40. doi: 10.3109/00365513.2012.755739.
Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005;115(5):561-5. doi: 10.1542/peds.2004-1832.
Jain V, Jana M, Upadhyay B, Ahmad N, Jain O, Upadhyay AD, et al. Prevalence, clinical & biochemical correlates of non-alcoholic fatty liver disease in overweight adolescents. Indian J Med Res. 2018;148(3):291-301. doi: 10.4103/ijmr.IJMR_1966_16.
Niriella MA, Kasturiratne A, Pathmeswaran A, De Silva ST, Perera KR, Subasinghe S, et al. Lean non-alcoholic fatty liver disease (lean NAFLD): Characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka. Hepatol Int. 2019;13(3)314-22. doi: 10.1007/s12072-018-9916-4.
Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003;143(4):500-5. doi: 10.1067/S0022-3476(03)00325-1.
Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008;118(3):277-83. doi: 10.1161/CIRCULATIONAHA.107.739920.
Han X, Xu P, Zhou J, Liu Y, Xu H. Fasting C-peptide is a significant indicator of nonalcoholic fatty liver disease in obese children. Diabetes Res Clin Pract. 2020;160:108027. doi:10.1016/j.diabres.2020.108027.
Mohamed RZ, Jalaludin MY, Anuar Zaini A. Predictors of non-alcoholic fatty liver disease (NAFLD) among children with obesity. J Pediatr Endocrinol Metab. 2020;33(2):247-53. doi: 10.1515/jpem-2019-0403.
Yu EL, Golshan S, Harlow KE, Angeles JE, Durelle J, Goyal NP, et al. Prevalence of nonalcoholic fatty liver disease in children with obesity. J Pediatr. 2019;207:64-70. doi: 10.1016/j.jpeds.2018.11.021.
Petta S, Camma C, Cabibi D, Di Marco V, Craxi A. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011;34(7):757-66. doi: 10.1111/j.1365-2036.2011.04788.x.
Sullivan JS, Le MT, Pan Z, Rivard C, Love-Osborne K, Robbins K, et al. Oral fructose absorption in obese children with non-alcoholic fatty liver disease. Pediatr Obes. 2015;10(3):188-95. doi: 10.1111/ijpo.238.
Mosca A, Nobili V, De Vito R, Crudele A, Scorletti E, Villani A, et al. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. J Hepatol. 2017;66(5):1031-6. doi: 10.1016/j. jhep.2016.12.025.
Wan X, Xu C, Lin Y, Lu C, Li D, Sang J, et al. Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome-dependent mechanism. J Hepatol. 2016;64(4):925-32. doi: 10.1016/j.jhep.2015.11.022.
Choi YJ, Shin HS, Choi HS, Park JW, Jo I, Oh ES, et al. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab Invest. 2014;94(10):1114-25. doi: 10.1038/labinvest.2014.98.
Ney DM, Yang H, Smith SM, Unterman TG. High-calorie total parenteral nutrition reduces hepatic insulin-like growth factor-I mRNA and alters serum levels of insulin-like growth factor-binding protein-1, -3, -5, and -6 in the rat. Metabolism. 1995;44(2):152-60. doi: 10.1016/0026-0495(95)90258-9.
Kokoszko A, Dabrowski J, Lewinski A, Karbownik-Lewinska M. Protective effects of GH and IGF-I against iron-induced lipid peroxidation in vivo. Exp Toxicol Pathol. 2008;60(6):453-8. doi: 10.1016/j.etp.2008.04.012.
Garcia-Fernandez M, Delgado G, Puche JE, Gonzalez-Baron S, Castilla Cortazar I. Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidative damage in aging rats. Endocrinology. 2008;149(5):2433-42. doi: 10.1210/en.2007-1190.
Savastano S, Di Somma C, Pizza G, De Rosa A, Nedi V, Rossi A, et al. Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. J Transl Med. 2011;9:136. doi: 10.1186/1479-5876-9-136.
Chen C, Zhu Z, Mao Y, Xu Y, Du J, Tang X, et al. HbA1c may contribute to the development of non-alcoholic fatty liver disease even at normal-range levels. Biosci Rep. 2020;40(1):20193996. doi: 10.1042/BSR20193996.
Lin TC, Lee HM, Seo HN, Oh JS, Kong HR, Cho SA, et al. Correlation between non-alcoholic fatty liver disease and hemoglobin A1c level in adult males without diabetes. Korean J Fam Pract. 2018;8(1):131-5. doi: 10.21215/kjfp.2018.8.1.131.
Ma H, Xu C, Xu L, Yu C, Miao M, Li Y. Independent association of HbA1c and nonalcoholic fatty liver disease in an elderly Chinese population. BMC Gastroenterol. 2013;13:3. doi: 10.1186/1471-230X-13-3.
How to Cite
Copyright (c) 2021 Holistence Publications
This work is licensed under a Creative Commons Attribution 4.0 International License.
When the article is accepted for publication in the HSQ authors transfer all copyright in the article to the Holistence Academy Ar-Ge Yazılım Yayıncılık Eğitim Danışmanlık ve Organizasyon Ticaret Ltd. Şti.The authors reserve all proprietary right other than copyright, such as patent rights.
Everyone who is listed as an author in this article should have made a substantial, direct, intellectual contribution to the work and should take public responsibility for it.
This paper contains works that have not previously published or not under consideration for publication in other journals.