비만한 한국 소아청소년에서 간 내 지방량과 흑색가시세포증 중증도와의 상관관계 = Association of Hepatic Fat Deposition and Severity of Acanthosis Nigricans in Children and Adolescents with Obesity

국문 초록 (Abstract)

연구배경: 비만한 소아청소년에서 인슐린 저항성과 흑색가시포증 또는 간 내 지방량과의 연관성에 대한 연구는 이루어졌으나 흑색가시세포증 중증도에 따른 간 내 지방량을 비교한 연구는 많지 않으며, 특히 소아청소년에서 진행된 연구는 거의 없다. 이에 본 연구는 자기공명영상을 활용하여 국내 비만한 소아청소년에서 흑색가시세포증 중증도에 따른 간 내 지방량의 상관관계를 살펴보고자 하였다.
방법: 본 연구는 소아청소년 체중 조절 중재 프로그램인 ICAAN 연구에 참여한 7–16세 소아청소년 총 225명(남 154명, 여 71명)을 분석하였으며, 모든 대상자는 신체계측, 혈액 검사, 자기공명영상를 통한 간 내 지방량, 복부내장지방량을 측정하였다. 흑색가시세포증의 중증도에 따라 3개의 군으로 나누었으며, 공분산분석 및 일반 선형 회귀 모델을 활용하여 중증도에 따른 간 내 지방량과의 선형 관계 여부를 확인하였다.
결과: 흑색가시세포증의 각 군을 성별, 연령으로 보정하여 비교한 결과 흑색가시세포증의 중증도가 높은 그룹으로 갈수록 간 내 지방량(%)은 유의하게 증가하는 경향을 보임을 확인하였다(그룹 1: 11.63±1.07, 그룹2: 15.40±1.17, 그룹 3: 23.00±1.95; P for trend< 0.001). 또한 BMI z-score (P for trend<0.001), HOMA-IR (P for trend= 0.011), 복부내장지방량(P for trend<0.001)을 각각 다른 모델에 추가하여 보정하였을 때에도 유의하게 증가하는 경향을 보임을 확인하였다.
결론: 국내의 비만이 동반된 소아청소년에서 흑색가시세포증은 인슐린 저항성 및 대사증후군 위험군뿐 아니라 지방간질환 여부를 추정하는 데 도움이 될 수 있는 간접적인 지표로 활용될 수 있을 것으로 생각된다.

다국어 초록 (Multilingual Abstract)

Background: This study aimed to investigate the association between hepatic fat deposition and the severity of acanthosis nigricans (AN) in Korean children and adolescents with obesity using magnetic resonance imaging (MRI).
Methods: A total of 225 participants (154 males and 71 females) aged 7–16 years were recruited between 2019 and 2020 from the Intervention for Childhood and Adolescents obesity via Activity and Nutrition (ICAAN) study. All participants underwent physical assessment and blood tests, and MRI was used to measure hepatic fat (%) and visceral adipose tissue (VAT, cm2) deposition. The participants were categorized into 3 groups according to the severity of AN: grade 0 (n=107), grade 1–3 (n=88), and grade 4 (n=30). After correcting for covariates, the mean deposition of hepatic fat was compared according to the severity of AN using analysis of covariance and linear regression model.
Results: The proportion of hepatic fat increased significantly with the severity of AN (Group 1: 11.63±1.07, Group 2: 15.0±1.17, Group 3: 23.0±1.95, P for trend <0.001). In addition, a significant increase in hepatic fat (%) with the severity of AN was observed when body mass index z-score (P for trend <0.001), homeostasis model assessment for insulin resistance (P for trend=0.011), and VAT (P for trend <0.001) were included in the model.
Conclusion: Hepatic fat is positively correlated with the severity of AN in children and adolescents with obesity, suggesting that AN may be an efficacious indirect indicator for estimating the presence of insulin resistance, metabolic syndrome, and fatty liver disease.

참고문헌 (Reference)

• 1 이병규 ; 박경희 ; 서영균 ; 노혜미 ; 송홍지 ; 백유진 ; 박미정 ; 조아라, "비만한 한국 소아청소년에서 흑색가시세포증 정도에 따른 인슐린 저항성과 비만 정도" 대한가정의학회 10 (10): 332-337, 2020
• 2 Anderson EL, "Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence : the ALSPAC study" 61 : 626-632, 2014
• 3 Papandreou D, "Update on non-alcoholic fatty liver disease in children" 26 : 409-415, 2007
• 4 Kahn CR, "The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man" 294 : 739-745, 1976
• 5 Eckel RH, "The metabolic syndrome" 365 : 1415-1428, 2005
• 6 김재현 ; 윤성하 ; 황승식 ; 심정옥 ; 채현욱 ; 이연주 ; 이지혁 ; 김순철 ; 임도희 ; 양세원 ; 오경원 ; 문진수, "The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects" 대한소아청소년과학회 61 (61): 135-149, 2018
• 7 Donnelly KL, "Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease" 115 : 1343-1351, 2005
• 8 Guran T, "Significance of acanthosis nigricans in childhood obesity" 44 : 338-341, 2008
• 9 Utzschneider KM, "Review : the role of insulin resistance in nonalcoholic fatty liver disease" 91 : 4753-4761, 2006
• 10 Chang Y, "Prevalence of acanthosis nigricans in relation to anthropometric measures : community-based cross-sectional study in Korean pre-adolescent school children" 50 : 667-673, 2008
• 11 Angulo P, "Obesity and nonalcoholic fatty liver disease" 65 (65): S57-S63, 2007
• 12 Marchesini G, "Nonalcoholic fatty liver disease : a feature of the metabolic syndrome" 50 : 1844-1850, 2001
• 13 Shaunak M, "Non-alcoholic fatty liver disease and childhood obesity" 106 : 3-8, 2021
• 14 Weiss R, "Metabolic complications of childhood obesity : identifying and mitigating the risk" 31 (31): S310-S316, 2008
• 15 Schwimmer JB, "Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease" 61 : 1887-1895, 2015
• 16 강성희 ; 이혜원 ; Jeong-Ju Yoo ; 조유리 ; 김승업 ; Tae Hee Lee ; Byoung Kuk Jang ; Sang Gyune Kim ; Sang Bong Ahn ; Haeryoung Kim ; Dae Won Jun ; 최준일 ; Do Seon Song ; Won Kim ; Soung Won Jeong ; 김문영 ; 고홍 ; 정수진 ; Jin Woo Lee ; Yong Kyun Cho ; The Korean Association for the Study of the Liver (KASL), "KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease" 대한간학회 27 (27): 363-401, 2021
• 17 Hirschler V, "Is acanthosis nigricans a marker of insulin resistance in obese children" 25 : 2353-, 2002
• 18 Bugianesi E, "Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease : sites and mechanisms" 48 : 634-642, 2005
• 19 Wolfrum C, "Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes" 432 : 1027-1032, 2004
• 20 Kelley DE, "Fatty liver in type 2 diabetes mellitus : relation to regional adiposity, fatty acids, and insulin resistance" 285 : E906-E916, 2003
• 21 Seppälä-Lindroos A, "Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men" 87 : 3023-3028, 2002
• 22 Middleton MS, "Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease" 67 : 858-872, 2018
• 23 Kiess W, "Childhood obesity at the crossroads" 28 : 481-484, 2015
• 24 Yoon HJ, "Causal relationship of non-alcoholic fatty liver disease with obesity and insulin resistance" 15 : 76-81, 2014
• 25 Phiske MM, "An approach to acanthosis nigricans" 5 : 239-249, 2014
• 26 Ng HY, "Acanthosis nigricans in obese adolescents : prevalence, impact, and management challenges" 8 : 1-10, 2016
• 27 Kutlubay Z, "Acanthosis nigricans : a fold(intertriginous)dermatosis" 33 : 466-470, 2015
• 28 Schwartz RA, "Acanthosis nigricans" 31 : 1-19, 1994
• 29 고영권 ; 이재희 ; 김은영 ; 문경래, "Acanthosis Nigricans as a Clinical Predictor of Insulin Resistancein Obese Children" 대한소아소화기영양학회 19 (19): 251-258, 2016
• 30 Burke JP, "A quantitative scale of acanthosis nigricans" 22 : 1655-1659, 1999