Fetuin-A、Fetuin-B及胰岛素抵抗指数对非酒精性脂肪性肝病的预测价值
DOI: 10.12449/JCH240409
Value of Fetuin-A, Fetuin-B, and insulin resistance index in predicting nonalcoholic fatty liver disease
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摘要:
目的 探讨血清Fetuin-A、Fetuin-B联合胰岛素抵抗指数(HOMA-IR)对非酒精性脂肪性肝病(NAFLD)的预测价值。 方法 连续选取2020年6月—2021年6月大理大学第一附属医院消化内科就诊的120例NAFLD患者和体检中心的120例健康体检人群为研究对象,收集其临床数据资料,并检测血清Fetuin-A、Fetuin-B水平。计量资料两组间比较采用成组t检验或Mann-Whitney U检验;计数资料两组间比较采用χ2检验。多因素Logistic回归分析NAFLD患者的危险因素。构建受试者工作特征曲线(ROC曲线)评估Fetuin-A、Fetuin-B联合HOMA-IR对NAFLD患者的预测效能。 结果 NAFLD组患者的体质量指数、收缩压、舒张压、ALT、AST、空腹血糖、空腹胰岛素、甘油三酯、HOMA-IR、Fetuin-A和Fetuin-B等均高于健康对照组(P值均<0.05)。多因素Logistic回归分析显示Fetuin-A(OR=1.010,95%CI:1.001~1.020,P<0.05)、Fetuin-B(OR=1.113,95%CI:1.021~1.214,P<0.05)和HOMA-IR(OR=24.053,95%CI:2.624~220.470,P<0.05)是NAFLD的独立危险因素。ROC曲线显示,Fetuin-A、Fetuin-B、HOMA-IR、Fetuin-A联合Fetuin-B、Fetuin-A联合HOMA-IR、Fetuin-B联合HOMA-IR以及三者联合预测NAFLD的ROC曲线下面积分别为0.637(95%CI:0.551~0.722)、0.853(95%CI:0.796~0.912)、0.837(95%CI:0.763~0.912)、0.853(95%CI:0.795~0.911)、0.843(95%CI:0.770~0.916)、0.922(95%CI:0.877~0.967)和0.922(95%CI:0.877~0.966)。 结论 Fetuin-A、Fetuin-B对NAFLD有一定的预测价值,Fetuin-B联合HOMA-IR的预测价值更高。 -
关键词:
- α-2-HS-糖蛋白 /
- 胎球蛋白B /
- 胰岛素抵抗 /
- 非酒精性脂肪性肝病
Abstract:Objective To investigate the value of serum Fetuin-A and Fetuin-B combined with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in predicting nonalcoholic fatty liver disease (NAFLD). Methods A total of 120 patients with NAFLD who attended Department of Gastroenterology, The First Affiliated Hospital of Dali University, from June 2020 to June 2021, and 120 healthy individuals who underwent physical examination at Physical Examination Center during the same period of time were enrolled as subjects, and clinical data were collected from all subjects. The serum levels of Fetuin-A and Fetuin-B were measured. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the multivariate Logistic regression analysis was used to assess the risk factors for NAFLD. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive efficacy of Fetuin-A and Fetuin-B combined with HOMA-IR in NAFLD patients. Results Compared with the healthy control group, the NAFLD group had significantly higher levels of body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminotransferase, fasting blood glucose, fasting insulin, triglycerides, HOMA-IR, Fetuin-A, and Fetuin-B (all P<0.05). The multivariate Logistic regression analysis showed that Fetuin-A (odds ratio [OR]=1.010, 95% confidence interval [CI]: 1.001 — 1.020, P<0.05), Fetuin-B (OR=1.113, 95%CI: 1.021 — 1.214, P<0.05), and HOMA-IR (OR=24.053, 95%CI: 2.624 — 220.470, P<0.05) were independent risk factors for NAFLD. The ROC curve analysis showed that Fetuin-A, Fetuin-B or HOMA-IR alone had an area under the ROC curve (AUC) of 0.637 (95%CI: 0.551 — 0.722), 0.853 (95%CI: 0.796 — 0.912), and 0.837 (95%CI: 0.763 — 0.912), respectively, and Fetuin-A combined with Fetuin-B, Fetuin-A combined with HOMA-IR, and Fetuin-B combined with HOMA-IR had an AUC of 0.853 (95%CI: 0.795 — 0.911), 0.843 (95%CI: 0.770 — 0.916), 0.922 (95%CI: 0.877 — 0.967), respectively, while the combination of these three indicators had an AUC of 0.922 (95%CI: 0.877 — 0.966). Conclusion Fetuin-A and Fetuin-B have a certain value in predicting NAFLD, and Fetuin-B combined with HOMA-IR tends to have a higher predictive value. -
表 1 研究对象的一般特征描述
Table 1. Description of general characteristics of study subjects
指标 NAFLD组(n=120) 健康对照组(n=120) 统计值 P值 男性[例(%)] 56(46.67) 50(41.67) χ2=0.608 0.435 年龄(岁) 51.08±13.07 38.76±10.92 t=-7.926 <0.001 本科及以上学历[例(%)] 35(29.17) 90(75.00) χ2=48.685 <0.001 BMI(kg/m2) 26.02±3.47 22.39±2.55 t=-9.234 <0.001 收缩压(mmHg) 129.46±21.71 115.33±15.73 t=-5.772 <0.001 舒张压(mmHg) 80.90±12.83 74.29±10.79 t=-4.318 <0.001 FPG(mmol/L) 5.14(4.45~6.82) 4.57(4.23~4.86) Z=-5.978 <0.001 FINS(μIU/mL) 5.78(4.29~6.72) 4.09(3.60~4.83) Z=-6.015 <0.001 ALT(U/L) 24.00(17.50~35.50) 16.00(12.00~23.00) Z=-5.526 <0.001 AST(U/L) 20.00(16.00~26.00) 17.00(15.00~20.25) Z=-2.552 <0.001 Alb(g/L) 42.60(38.55~46.10) 47.20(45.58~49.15) Z=10.017 <0.001 LDL-C(mmol/L) 2.65±0.72 2.81±0.74 t=1.690 0.157 HDL-C(mmol/L) 1.17±0.32 1.60±0.34 t=9.964 <0.001 TC(mmol/L) 4.80(4.17~5.46) 5.08(4.44~5.52) Z=0.731 0.104 TBil(mmol/L) 11.70(8.70~15.20) 13.15(10.17~16.52) Z=0.984 0.020 BUN(mmol/L) 5.21(4.21~6.50) 5.12(4.06~5.94) Z=-1.788 0.182 TG(mmol/L) 2.13(1.58~3.12) 1.28(0.93~1.77) Z=-5.140 <0.001 SUA(μmol/L) 352.00(289.00~407.00) 344.00(296.50~404.75) Z=0.103 0.816 Scr(μmol/L) 68.34±19.81 69.66±15.93 t=-0.170 0.373 HOMA-IR 1.32(1.06~1.64) 0.85(0.74~0.96) Z=-7.658 <0.001 Fetuin-A(μg/mL) 685.23(595.80~776.49) 601.36(534.56~668.06) Z=-7.344 <0.001 Fetuin-B(μg/mL) 81.44(72.41~100.88) 64.19(57.83~71.31) Z=-2.755 <0.001 表 2 多因素Logistic回归分析
Table 2. Multivariable Logistic regression analysis
指标 β值 标准误 Wald值 OR值 95%CI P值 常数项 -35.518 10.885 10.648 年龄 0.086 0.038 5.276 1.090 1.013~1.173 0.022 性别 1.670 1.282 1.696 5.310 0.430~65.511 0.193 教育程度 -1.208 1.261 0.917 0.299 0.025~3.538 0.338 BMI 0.886 0.460 3.700 2.424 0.983~5.977 0.054 收缩压 0.054 0.048 1.276 1.055 0.961~1.158 0.259 舒张压 -0.088 0.078 1.264 0.916 0.787~1.067 0.261 ALT 0.156 0.061 6.605 1.169 1.038~1.317 0.010 AST -0.023 0.058 0.153 0.978 0.872~1.096 0.695 HDL-C -8.646 4.714 3.365 0.002 0.001~1.809 0.067 TG -0.293 0.368 0.634 0.746 0.363~1.534 0.426 HOMA-IR 5.483 2.305 5.657 24.053 2.624~220.470 0.017 Fetuin-A 0.010 0.005 4.047 1.010 1.001~1.020 0.044 Fetuin-B 0.107 0.044 5.910 1.113 1.021~1.214 0.015 表 3 Fetuin-A、Fetuin-B联合HOMA-IR对NAFLD患者的预测价值
Table 3. Predictive value of Fetuin-A and Fetuin-B combined with HOMA-IR for NAFLD
预测指标 最佳截断值 敏感度(%) 特异度(%) AUC(95%CI) P值 Fetuin-A 569.06 76.5 43.9 0.637(0.551~0.722) 0.003 Fetuin-B 71.89 73.5 85.7 0.853(0.796~0.912) <0.001 HOMA-IR 1.025 75.0 89.8 0.837(0.763~0.912) <0.001 Fetuin-A联合Fetuin-B 0.46 75.0 84.7 0.853(0.795~0.911) <0.001 Fetuin-A联合HOMA-IR 0.47 70.6 93.9 0.843(0.770~0.916) <0.001 Fetuin-B联合HOMA-IR 0.40 80.9 91.8 0.922(0.877~0.967) <0.001 Fetuin-A、Fetuin-B联合HOMA-IR 0.40 80.9 91.8 0.922(0.877~0.966) <0.001 -
[1] YOUNOSSI ZM, GOLABI P, PAIK JM, et al. The global epidemiology of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH): A systematic review[J]. Hepatology, 2023, 77( 4): 1335- 1347. DOI: 10.1097/HEP.0000000000000004. [2] ESTES C, ANSTEE QM, ARIAS-LOSTE MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018, 69( 4): 896- 904. DOI: 10.1016/j.jhep.2018.05.036. [3] WU CM, ZHANG CY, XU HL, et al. Epidemiological research and diagnosis of nonalcoholic fatty liver disease in China[J]. China Med Herald, 2023, 20( 11): 158- 161. DOI: 10.20047/j.issn1673-7210.2023.11.36.吴车敏, 张从玉, 徐慧丽, 等. 我国非酒精性脂肪性肝病的流行病学研究和诊断现状分析[J]. 中国医药导报, 2023, 20( 11): 158- 161. DOI: 10.20047/j.issn1673-7210.2023.11.36. [4] SARDANA O, GOYAL R, BEDI O. Molecular and pathobiological involvement of fetuin-A in the pathogenesis of NAFLD[J]. Inflammopharmacology, 2021, 29( 4): 1061- 1074. DOI: 10.1007/s10787-021-00837-4. [5] CHEKOL ABEBE E, TILAHUN MUCHE Z, BEHAILE T/MARIAM A, et al. Role of fetuin-A in the pathogenesis of psoriasis and its potential clinical applications[J]. Clin Cosmet Investig Dermatol, 2022, 15: 595- 607. DOI: 10.2147/CCID.S356801. [6] STEFAN N, FRITSCHE A, WEIKERT C, et al. Plasma fetuin-A levels and the risk of type 2 diabetes[J]. Diabetes, 2008, 57( 10): 2762- 2767. DOI: 10.2337/db08-0538. [7] SONG AY, XU M, BI YF, et al. Serum fetuin-A associates with type 2 diabetes and insulin resistance in Chinese adults[J]. PLoS One, 2011, 6( 4): e19228. DOI: 10.1371/journal.pone.0019228. [8] SUN JR, ZHANG D, XU J, et al. Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: A meta-analysis[J]. Lipids Health Dis, 2020, 19( 1): 199. DOI: 10.1186/s12944-020-01365-w. [9] XIAO Y, SHU LL, WU XP, et al. Fatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages[J]. JCI Insight, 2021, 6( 7): e141814. DOI: 10.1172/jci.insight.141814. [10] OLIVIER E, SOURY E, RUMINY P, et al. Fetuin-B, a second member of the fetuin family in mammals[J]. Biochem J, 2000, 350( Pt 2): 589- 597. [11] MUSTAFA AI, KADAH AS, FAWZY EM, et al. Serum fetuin-A: A novel potential link between post-adolescent acne and insulin resistance[J]. J Clin Aesthet Dermatol, 2022, 15( 12): 33- 37. [12] DENG WJ, GU J, ZUO LJ, et al. The level changes and influencing factors of serum fetuin-B in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease[J]. Chin J Diabetes, 2019, 27( 3): 198- 201. DOI: 10.3969/j.issn.1006-6187.2019.03.007.邓文娟, 谷君, 左丽娟, 等. 2型糖尿病合并非酒精性脂肪性肝病患者血清胎球蛋白B水平变化及影响因素分析[J]. 中国糖尿病杂志, 2019, 27( 3): 198- 201. DOI: 10.3969/j.issn.1006-6187.2019.03.007. [13] National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34( 5): 947- 957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34( 5): 947- 957. DOI: 10.3969/j.issn.1001-5256.2018.05.007. [14] YOUNOSSI ZM, HENRY L, BUSH H, et al. Clinical and economic burden of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Clin Liver Dis, 2018, 22( 1): 1- 10. DOI: 10.1016/j.cld.2017.08.001. [15] STEFAN N, HENNIGE AM, STAIGER H, et al. Alpha2-heremans-schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans[J]. Diabetes Care, 2006, 29( 4): 853- 857. DOI: 10.2337/diacare.29.04.06.dc05-1938. [16] CHEKOL ABEBE E, TILAHUN MUCHE Z, BEHAILE T/MARIAM A, et al. The structure, biosynthesis, and biological roles of fetuin-A: A review[J]. Front Cell Dev Biol, 2022, 10: 945287. DOI: 10.3389/fcell.2022.945287. [17] LI LN, SPRANGER L, STOBÄUS N, et al. Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss-weight maintenance[J]. Nutr Diabetes, 2021, 11( 1): 31. DOI: 10.1038/s41387-021-00174-z. [18] DI MINNO A, ZANOBINI M, MYASOEDOVA VA, et al. Could circulating fetuin A be a biomarker of aortic valve stenosis?[J]. Int J Cardiol, 2017, 249: 426- 430. DOI: 10.1016/j.ijcard.2017.05.040. [19] Low serum fetuin-a as a biomarker to predict pneumococcal necrotizing pneumonia and hemolytic uremic syndrome in children: Erratum[J]. Medicine, 2018, 97( 3): e9684. DOI: 10.1097/MD.0000000000009684. [20] ZHOU ZW, SUN MZ, JIN H, et al. Fetuin-A to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly[J]. Lipids Health Dis, 2020, 19( 1): 61. DOI: 10.1186/s12944-020-01251-5. [21] ZHAO LL, SHANG Y, LUO QZ, et al. Decreased plasma fetuin-A level as a novel bioindicator of poor prognosis in community-acquired pneumonia: A multi-center cohort study[J]. Front Med, 2022, 9: 807536. DOI: 10.3389/fmed.2022.807536. [22] DIAO WQ, SHEN N, DU YP, et al. Fetuin-B(FETUB): A plasma biomarker candidate related to the severity of lung function in COPD[J]. Sci Rep, 2016, 6: 30045. DOI: 10.1038/srep30045. [23] YURTCU N, ORAL S, CELIK S, et al. Predıctıve value of pregnancy of follıcular fluıd fetuın-A and-B levels ın infertıle women after intra-cytoplasmic sperm injection[J]. J Obstet And Gynaecol, 2022, 48( 1): 178- 187. DOI: 10.1111/jog.15070. [24] LIU SS, XIAO JH, ZHAO ZZ, et al. Systematic review and meta-analysis of circulating fetuin-a levels in nonalcoholic fatty liver disease[J]. J Clin Transl Hepatol, 2021, 9( 1): 3- 14. DOI: 10.14218/JCTH.2020.00081. [25] LU CW, LEE YC, CHIANG CH, et al. Independent dose-response associations between fetuin-A and lean nonalcoholic fatty liver disease[J]. Nutrients, 2021, 13( 9): 2928. DOI: 10.3390/nu13092928. [26] BALLESTRI S, MESCHIARI E, BALDELLI E, et al. Relationship of serum fetuin-a levels with coronary atherosclerotic burden and NAFLD in patients undergoing elective coronary angiography[J]. Metab Syndr Relat Disord, 2013, 11( 4): 289- 295. DOI: 10.1089/met.2012.0149. [27] IX JH, SHARMA K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: The roles of fetuin-A, adiponectin, and AMPK[J]. J Am Soc Nephrol, 2010, 21( 3): 406- 412. DOI: 10.1681/ASN.2009080820. [28] LANTHIER N, LEBRUN V, MOLENDI-COSTE O, et al. Liver fetuin-A at initiation of insulin resistance[J]. Metabolites, 2022, 12( 11): 1023. DOI: 10.3390/metabo12111023. [29] PETER A, KOVAROVA M, STAIGER H, et al. The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans[J]. Am J Physiol Endocrinol Metab, 2018, 314( 3): E266- E273. DOI: 10.1152/ajpendo.00262.2017. [30] CHOI JW, LIU H, MUKHERJEE R, et al. Downregulation of fetuin-B and zinc-α2-glycoprotein is linked to impaired fatty acid metabolism in liver cells[J]. Cell Physiol Biochem, 2012, 30( 2): 295- 306. DOI: 10.1159/000339065. [31] DABROWSKA AM, TARACH JS, WOJTYSIAK-DUMA B, et al. Fetuin-A(AHSG) and its usefulness in clinical practice. Review of the literature[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2015, 159( 3): 352- 359. DOI: 10.5507/bp.2015.018. [32] ZHAO CL, SHANG DF, ZHOU C, et al. Mechanism of lipid metabolism mediated by hepatokines and adipokines in nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2023, 39( 1): 168- 174. DOI: 10.3969/j.issn.1001-5256.2023.01.026.赵晨露, 尚东方, 周铖, 等. 肝因子和脂肪因子介导的脂代谢在非酒精性脂肪性肝病中的作用机制[J]. 临床肝胆病杂志, 2023, 39( 1): 168- 174. DOI: 10.3969/j.issn.1001-5256.2023.01.026.