Meltem GÜMÜŞ, Alaaddin YORULMAZ, Hakan CANDAN, Anna Carina ERGANİ, Reyhan GÜMÜŞTEKİN, Fuat BUĞRUL, Hüsamettin VATANSEV, Halil Haldun EMİROĞLU

Çocukluk çağı metabolik disfonksiyonla ilişkili yağlı karaciğer hastalığında insülin direnci ve kardiyovasküler risk faktörleri

Amaç: Bu çalışmanın amaçları: Metabolik disfonksiyon- ilişkili yağlı karaciğer hastalığı (MASLD) varlığından şüphelenilen olguların erken tanısı için daha pratik bir yol olması amacıyla biyokimyasal indeksler geliştirmek ve obez çocuklarda MASLD gibi önemli bir hastalığı tanımamızı sağlayacak kolay biyobelirteçler geliştirmektir. Gereç ve Yöntem: Ocak 2020-Mart 2023 tarihleri arasında ESPGHAN 2012 kılavuzu referans alınarak tanı konulan 6-18 yaş arası MASLD tanısı konulan 90 hasta ve 70 sağlıklı gönüllü çocuk dâhil edilmiştir. Yaş, cinsiyet, antropometrik ölçümler ve biyokimyasal analizler belirlendi. HOMA-IR, HOMA-β, FGIR, QUICKI, AIP, vb. gibi bazı biyokimyasal oranlar hesaplandı. Bulgular: Hasta grubunda 40 (%44) kız ve 50 (%55.6) erkek vardı. AST, GGT, TSH, LDL, TG, Total Kolesterol, HDL, FAS, İnsülin, HOMA-IR, HOMA-β, QUICKI skoru, FGIR, MHO, LHO, LKO, THO, AST/ALT oranları ve Sistemik immun inflamatuar indeks değerleri arasında pozitif korelasyon bulunmuştur. HOMA-IR değerinin ROC analizi sonuçları 2,94 olarak alınmış, tanı değerinin özgüllüğü %52,20 ve duyarlılığı %80,0 olarak bulunmuştur. Sonuç: MASLD günümüzde giderek artan bir seyir göstermektedir. Biyokimyasal parametrelerin ve elde ettiğimiz biyobelirteçlerin MASLD ile insülin direncini belirlemek ve komplikasyonları tahmin etmek için doğru ve faydalı indeksler arasında olduğu sonucuna varılmıştır.

Anahtar Kelimeler:

Metabolik Disfonksiyonla İlişkili Yağlı Karaciğer Hastalığı, Bİyobelirteç, Çocuk

Insulin resistance and cardiovascular risk factors in childhood metabolic dysfunction-associated steatotic liver disease

Purpose: The objectives of the present study were to develop biochemical indices as a more practical way for the early diagnosis of cases with suspected metabolic dysfunction-assosiated steatotic liver disease (MASLD) and to develop easy biomarkers to enable clinicians to recognize MASLD in obese children. Materials and Methods: A total of 90 patients who had MASLD and 70 healthy volunteering children between the ages of 6-18 who were diagnosed with reference to the ESPGHAN 2012 Guideline between January 2020 and March 2023 were included. Age, gender, Anthropometric measurements and biochemical analysis were determined. Some Biochemical ratios such as HOMA-IR, HOMA-β, FGIR, QUICKI, AIP etc were calculated. Results: There were 40 (44.4%) girls and 50 (55.6%) boys in the patient group.A positive correlation was found between AST, GGT, TSH, LDL, TG, total cholesterol, HDL, FAS, insulin, HOMA-IR, HOMA-β, QUICKI score, FGIR, MHR, LHR, LKR, THR ALT/AST ratios and Systemic Immun Inflammatory Index values in the analysis. The ROC analysis results of the HOMA-IR value was taken as 2.94, the specificity of the diagnostic value was found to be 52.20% and the sensitivity was 80.0%. Conclusion: MASLD has an increasing trend today.Based on the design of the present study, it was concluded that almost all of the biochemical parameters and biomarkers obtained are among the most accurate and useful indices to determine MASLD and IR and predict complications.

Keywords:

Metabolic Dysfunction Associated Steatotic Liver Disease, Biomarker, Chıld,

PDF

___

Margolis-Gil M, Yackobovitz-Gavan M, Phillip M, Shalitin S. Which predictors differentiate between obese children and adolescents with cardiometabolic complications and those with metabolically healthy obesity? Pediatr Diabetes. 2018;19:1147-55.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128•9 million children, adolescents, and adults. Lancet. 2017:16;390:2627-42.
T.C. Sağlık Bakanlığı. Türkiye Beslenme Ve Sağlık Araştırması 2010: Beslenme Durumu Ve Alışkanlıklarının Değerlendirilmesi Sonuç Raporu. Ankara, T.C Sağlık Bakanlığı, 2014.
World Health Organization Childhood Overweight And Obesity. Geneva, World Health Organization, 2016.
Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:99-112.
Pappachan JM, Babu S, Krishnan B, Ravindran NC. Nonalcoholic fatty liver disease: a clinical update. J Clin Transl Hepatol. 2017;5:384-93.
Fujii H, Kawada N. Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol. 2012;47:215-25.
Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, Bas F. Growth references for Turkish children aged 6 to 18 years. Acta Paediatrica. 2006;95:1635-41.
Özön ZA. Metabolik sendrom. Turk Clin J Pediatr Sci. 2015;11:42-8.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insülin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetelogia. 1985;28:412-9.
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.
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for evaluating insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.
Dobiasova M. Atherogenoc index of plasma [log(- triglycerides/HDL-cholesterol)]: theoretical and practical implications. Clin Chem. 2004;50:1113–15.
Berg JE, Hostmark AT. Cadiovascular risk determination: discrepancy between total cholesterol evaluation and two compound laboratory indices in Norway. J Epidemiol Community Health. 1994;48:338–43.
Colquhoun D, Keech A, Hunt D, Marschner I, Simes J, Glasziou et al. Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study. European heart jour. 2004;25:771-7.
Simental-Mendia LE, Rodriguez-Moran M, Guerrero-Romero F. Te product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008;6:299-304.
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 metaanalysis. PLoS One. 2015;10:e0140908.
Akcam M, Boyaci A, Pirgon O, Koroglu M, Dundar BN. Importance of the liver ultrasound scores in pubertal obese children with nonalcoholic fatty liver disease. Clin Imaging. 2013;37:504–8.
Cassader M, Gambino R, Musso G, Depetris N, Mecca F, Cavallo-Perin P et al. Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic Steatohepatitis patients. Lipids. 2001;36:1117-24.
Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia. 2009;13:9-19.
Sentürk O. Non alkolik yağlı karaciğer hastalığı (NAYKH). Folia. 2004;4:12-20.
Marchesini G, Bugianesi E, Forlani G, Cerelli F, Lenzi M, Manini R et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology.2003;37:917-23.
Fu JF, Shi HB, Liu LR, Jiang P, Liang L, Wang CL et al. Non-alcoholic fatty liver disease: an early mediator predicting metabolic syndrome in obese children? World J Gastroenterol. 2011:17:735.
Pirgon O, Cekmez F, Bilgin H, Eren E, Dundar B. Low 25-hydroxy-vitamin D level is associated with insulin sensitivity in obese adolescents with non-alcoholic fatty liver disease. Obes Res Clin Pract. 2013;7:275–83.
Denzer C, Karges B, Nake A, Rosenbauer J, Schober E, Schwab KO et al. Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol. 2013;168:601–8.
Siqueira ACG, Cotrim HP, Rocha R, Carvalho FM, Freita LAR, Barreto D et al. Nonalcoholic fatty liver disease and ,insulin resistance: importance of risk factors and histological spectrum. Eur J Gastroenterol Hepatol. 2005;17:837-41.
Duvnjak M, Lerotic I, Barsic N, Tomasic V, Jukic LV, Velagic V. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J Gastroenterol. 2007;13:4539–50.
Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol. 1979;236:E667-77.
Gokcel A, Baltali M, Tarim E, Bagis T, Gumurdulu Y, Karakose H, et al. Detection of insülin resistance in Turkish adults: a hospital – based study. Diabetes Obes Metab. 2003;5:126-30.
De Luis DA, Izaola O, Primo D, de la Fuente B, Aller R. Polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CNR2) reveals effects on body weight and insulin resistance in obese subjects. Endocrinol Diabetes Nutr. 2017;64:440-5.
Murdock DK, Olson KJ, Juza RM, Hendricks BL. Effect of body mass index on insulin resistance and lipids in prepubertal and postpubertal children: SCHOOL observations. J Cardiometab Syndr. 2006;1:242-7.
Yang HR, Yi DY, Choi HS. Comparison between a pediatric health promotion center and a pediatric obesity clinic in detecting metabolic syndrome and non-alcoholic fatty liver disease in children. J Korean M Scı. 2014;29:1672-7.
Armstrong MJ, Houlihan DD, Bentham L, Shaw JC, Cramb R, Olliff S et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J Hepatol. 2012:56;234–40.
Bishnu J, Subita L, Anil D, Ramesh R. Comparison of liver enzymes and sonological grading in nonalcoholic fatty liver. Asian J Med Sci. 2020;11:42-5.
Schwimmer JB, Newton KP, Awai HI, Choi LJ, Garcia MA, Ellis LL et al. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non‐alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38:1267-77.
Lee YJ, Lee HR, Lee JH, Shin YH and Shim JY. Association between serum uric acid and non-alcoholic fatty liver disease in Korean adults. Clin Chem Lab Med. 2010;48:175-80.
Fu JF, Shi HB, Liu LR, Jiang P, Liang L, Wang CL et al. Non-alcoholic fatty liver disease: an early mediator predicting metabolic syndrome in obese children? World J Gastroenterol. 2011;17:735-72.
Souza MRdA, Diniz MdFFdM, Medeiros-Filho JEMd, Araújo MSTd. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease. Arq Gastroenterol. 2012;49:89-96.
Madan K, Batra Y, Gupta SD, Chander B, Rajan KD, Tewatia MS et al. Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians. World J Gastroenterol. 2006;12:3400-5.
Freedman DS, Patel DA, Srinivasan SR, Chen W, Tang R, Bond MG et al. The contribution of childhood obesity to adult carotid intima-media thickness: the Bogalusa Heart Study. Int J Obes (Lond). 2008;32:749-56.
Elmaogulları S, Tepe D, Ucakturk SA, Karaca Kara F, Demirel F. Prevalence of dyslipidemia and associated factors in obese children and adolescents. J Clin Res Pediatr Endocrinol. 2015;7:228-34.
Nigam P, Bhatt SP, Misra A, Vaidya M, Dasgupta J, Chadha DS. Non-alcoholic fatty liver disease is closely associated with sub-clinical inflammation: a case-control study on Asian Indians in North India. PLoS One. 2013;8:e49286.
Ozhan H, Aydin M, Yazici M, Yazgan O, Basar C, Gungor A et al. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets. 2010;21:29-32.
Toledo FG, Sniderman AD, Kelley DE. Influence of hepatic steatosis (fatty liver) on severity and composition of dyslipidemia in type 2 diabetes. Diabetes Care. 2006;29:1845–50.
Nobili V, Alkhouri N, Bartuli A, et al. Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatric Res. 2010;67:665-70.
Wang K, Shan S, Zheng H, Zhao X, Chen C, Liu C et al. Non-HDL-cholesterol to HDL-cholesterol ratio is a better predictor of new-onset nonalcoholic fatty liver disease than non-HDL-cholesterol: a cohort study. Lipid Health Dis. 2018;19:196.
Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:27-38.
Olson K, Hendricks B, Murdock DK. The triglyceride to hdl ratio and its relationship to insulin resistance in pre and postpubertal children: observation from the Wausau SCHOOL Project. Cholesterol. 2012;2012:794252.
Di Bonito P, Moio N, Scilla C, Cavuto, Sibilio G, Santguigno et al. Usefulness of the high triglyceride-to-HDL cholesterol ratio to identify cardiometabolic risk factors and preclinical signs of organ damage in outpatient children. Diabetes Care. 2012;35:158-62.
Giannini C, Santoro N, Caprio S, Kim G, Lartaud D, Shaw M et al. The triglyceride-to-HDL cholesterol ratio: association with insulin resistance in obese youths of different ethnic backgrounds. Diabetes Care. 2011;34:1869–74.
Guerrero-Romero F, Simental-Mendia LE, Gonzalez-Ortiz M, Martinez-Abundis E, Ramos-Zavala M, Hernandez-Gonzalez SO, et al. The product of triglycerides and glucose, a simple measure of insulin sensitivity. comparison with the euglycemic hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95:3347–51.
Wang L, Cong HL, Zhang JX, Hu YC, Wei A, Zhang YY et al. Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome. Cardiovasc Diabetol. 2020;19:80.