慢性丙型肝炎患者胎球蛋白A变化及其与胰岛素抵抗关系研究
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摘要
背景丙型肝炎病毒(HCV)感染引起的慢性感染性肝脏疾病与胰岛素抵抗(IR)存在一定联系,但胎球蛋白A(fetuin-A)在慢性丙型肝炎(CHC)患者发生IR的研究却鲜见报道。目的探究CHC患者fetuin-A变化及其与IR的关系。方法回顾性选取2009年6月—2011年2月温州医科大学附属第一医院收治的符合研究标准的CHC患者315例,作为CHC组;并依据BMI将CHC组患者分为BMI正常亚组(BMI:18～25 kg/m2,n=78)和BMI升高亚组(BMI>25 kg/m2,n=237)。选取同期在本院体检健康者100例为健康对照组。收集CHC组及健康对照组的一般资料(包括性别、年龄、体质量、身高、BMI)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGTP)、HCV-RNA、总胆红素、血红蛋白、白细胞计数、血小板计数、清蛋白(Alb)、总蛋白(TP)、总胆固醇、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油、空腹血糖、空腹胰岛素、空腹C肽、胰岛素抵抗指数(HOMA-IR)、胰岛素B细胞功能指数(HBCI)、空腹B细胞功能指数(FBCI)、胰岛素敏感指数(IAI)、fetuin-A、AST/ALT(AAR)、AST/血小板计数(APRI)。结果 CHC组ALT、AST、空腹胰岛素、空腹C肽、HOMA-IR、fetuin-A、AAR、APRI高于健康对照组,HDL-C低于健康对照组(P<0.05)。BMI正常亚组空腹胰岛素、HOMA-IR、HBCI、FBCI、fetuin-A低于BMI升高亚组(P<0.05)。CHC患者fetuin-A与BMI(r=0.210,P=0.031)、HOMA-IR(r=0.389,P=0.023)呈正相关,与ALT、AST、GGTP、空腹胰岛素、空腹C肽、HDL-C、空腹血糖、HBCI、FBCI、AAR、APRI无线性相关关系(r值分别为0.102、0.184、0.276、0.162、0.151、0.123、0.179、0.015、0.049、0.017、-0.038,P值分别为0.335、0.181、0.104、0.124、0.154、0.337、0.327、0.883、0.645、0.923、0.830)。结论 CHC患者体内存在IR和部分血脂代谢紊乱,fetuin-A升高,且fetuin-A与IR关系密切。
Background Chronic infectious liver disease caused by HCV infection is associated with insulin resistance(IR),but the study of fetuin-A in IR from patients with chronic hepatitis C(CHC) has rarely been reported.Objective To investigate the level of fetuin-A and the relationship between fetuin-A and IR in patients with CHC.MethodsThree hundred fifteen patients with CHC admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2009 to February 2011 were retrospectivly selected as CHC group.According to BMI,patients in CHC group were divided into normal BMI subgroup(BMI:18-25 kg/m2,n=78) and elevated BMI subgroup(BMI>25 kg/m2,n=237).A hundred healthy people who underwent physical examination in the hospital during the same period were selected as healthy control group.General information(including sex,age,weight,height,BMI),ALT,AST,gamma-glutamyl transpeptidase(GGTP),HCV-RNA, total bilirubin,hemoglobin,white blood cell count,platelet count,Alb,TP,total cholesterol,HDL-C,LDL-C,triglyceride,fasting blood glucose,fasting insulin,fasting C-peptide,insulin resistance index(HOMA-IR),HBCI,FBCI,IAI,fetuin-A,AST/ALT ratio(AAR),AST/platelet count ratio(APRI) of CHC group and healthy control group were collected.Results ALT,AST,GGTP,fasting insulin,fasting C-peptide,HOMA-IR,fetuin-A,AAR,APRI in CHC group were higher than those in healthy control group,and HDL-C was higher than that in healthy control group(P<0.05).Fasting insulin,HOMA-IR,HBCI,FBCI,and fetuin-A in normal BMI subgroup were higher than those of elevated BMI subgroup(P<0.05).Fetuin-A of CHC patients was positively related to BMI(r=0.210,P=0.031) and HOMA-IR(r=0.389,P=0.023),while it was not linear related to other indicators,such as ALT,AST,GGTP,HDL-C,fasting blood glucose,fasting insulin,fasting C-peptide,HBCI,FBCI,AAR and APRI(r values were 0.102,0.184,0.276,0.162,0.151,0.123,0.179,0.015,0.049,0.017,-0.038,respectively;P values were 0.335,0.181,0.104,0.124,0.154,0.337,0.327,0.883,0.645,0.923,0.830,respectively).Conclusion There is IR and certain lipid metabolism disorder in CHC patients,and fetuin-A is closely related to IR.
Background Chronic infectious liver disease caused by HCV infection is associated with insulin resistance(IR),but the study of fetuin-A in IR from patients with chronic hepatitis C(CHC) has rarely been reported.Objective To investigate the level of fetuin-A and the relationship between fetuin-A and IR in patients with CHC.MethodsThree hundred fifteen patients with CHC admitted to the First Affiliated Hospital of Wenzhou Medical University from June 2009 to February 2011 were retrospectivly selected as CHC group.According to BMI,patients in CHC group were divided into normal BMI subgroup(BMI:18-25 kg/m2,n=78) and elevated BMI subgroup(BMI>25 kg/m2,n=237).A hundred healthy people who underwent physical examination in the hospital during the same period were selected as healthy control group.General information(including sex,age,weight,height,BMI),ALT,AST,gamma-glutamyl transpeptidase(GGTP),HCV-RNA, total bilirubin,hemoglobin,white blood cell count,platelet count,Alb,TP,total cholesterol,HDL-C,LDL-C,triglyceride,fasting blood glucose,fasting insulin,fasting C-peptide,insulin resistance index(HOMA-IR),HBCI,FBCI,IAI,fetuin-A,AST/ALT ratio(AAR),AST/platelet count ratio(APRI) of CHC group and healthy control group were collected.Results ALT,AST,GGTP,fasting insulin,fasting C-peptide,HOMA-IR,fetuin-A,AAR,APRI in CHC group were higher than those in healthy control group,and HDL-C was higher than that in healthy control group(P<0.05).Fasting insulin,HOMA-IR,HBCI,FBCI,and fetuin-A in normal BMI subgroup were higher than those of elevated BMI subgroup(P<0.05).Fetuin-A of CHC patients was positively related to BMI(r=0.210,P=0.031) and HOMA-IR(r=0.389,P=0.023),while it was not linear related to other indicators,such as ALT,AST,GGTP,HDL-C,fasting blood glucose,fasting insulin,fasting C-peptide,HBCI,FBCI,AAR and APRI(r values were 0.102,0.184,0.276,0.162,0.151,0.123,0.179,0.015,0.049,0.017,-0.038,respectively;P values were 0.335,0.181,0.104,0.124,0.154,0.337,0.327,0.883,0.645,0.923,0.830,respectively).Conclusion There is IR and certain lipid metabolism disorder in CHC patients,and fetuin-A is closely related to IR.
引文
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[11]ALI S A,NASSIF W M,ABDELAZIZ D H.Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes:a case-control study[J].Clin Res Hepatol Gastroenterol,2016,40(4):465-470.DOI:10.1016/j.clinre.2015.12.003.
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[14]KAWAGUCHI T,YOSHIDA T,HARADA M,et al.Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3[J].Am J Pathol,2004,165(5):1499-1508.
[15]HICKMAN T J,POWELL E E,PRINS J B,et al.In overweight patients with chronic hepatitis C,circulating insulin is associated with hepatic fibrosis:implications for therapy[J].J Hepatol,2003,39(6):1042-1048.
[16]李光伟.胰岛素抵抗评估及其临床应用[J].中华老年多器官疾病杂志,2004,3(1):11-12.
[17]IKEDAY,SUEHIROT,NAKAMURAT,etal.Clinical significanceoftheinsulinresistanceindexasassessedby homeostasis model assessment[J].Endocr J,2001,48(1):81-86.
[18]GOUSTIN A S,ABOU-SAMRA A B.The"thrifty"gene encoding Ahsg/Fetuin-A meets the insulin receptor:insights into the mechanism of insulin resistance[J].Cell Signal,2011,23(6):980-990.DOI:10.1016/j.cellsig.2010.11.003.
[19]PESSIN J E,SALTIEL A R.Signaling pathways in insulin action:molecular targets of insulin resistance[J].J Clin Invest,2000,106(2):165-169.DOI:10.1172/JCI10582.
[20]GOUSTIN A S,DERAR N,ABOU-SAMRA A B.Ahsg-fetuin blocks the metabolic arm of insulin action through its interaction with the 95-kDβ-subunit of the insulin receptor[J].Cell Signal,2013,25(4):981-988.DOI:10.1016/j.cellsig.2012.12.011.
[21]陈婷,靳彦文,瞿秀华,等.胎球蛋白A的纯化及其对3T3-L1脂肪细胞胰岛素通路的抑制作用[J].解放军医学杂志,2010,35(7):819-822.CHEN T,JIN Y W,QU X H,et al.Purification of AHSG and its inhibition effect on insulin pathway of 3T3-L1 adipocyte[J].Med J Chin PLA,2010,35(7):819-822.
[22]张春梅,陈婷,李平,等.AHSG对胰岛素刺激下的HL-7702细胞中FAS、SREBP-1基因表达的影响[J].军事医学,2012,36(3):182-185,195.DOI:10.3969/j.issn.1674-9960.2012.03.005.ZHANG C M,CHEN T,LI P,et al.AHSG impact on expression of FAS and SREBP-1 genes of HL-7702 cells under insulin treatment[J].Military Medical Sciences,2012,36(3):182-185,195.DOI:10.3969/j.issn.1674-9960.2012.03.005.
[2]QIU N C,ZHANG Q,SONG X,et al.Impact of the hepatic branchofthevagusandRoux-en-Ygastricbypassonthe hypoglycemic effect and glucagon-like petide-1 in rats with type 2diabetes mellitus[J].J Surg Res,2014,191(1):123-129.DOI:10.1016/j.jss.2014.03.062.
[3]NAING C,MAK J W,AHMED S I,et al.Relationship between hepatitis C virus infection and type 2 diabetes mellitus:metaanalysis[J].World J Gastroenterol,2012,18(14):1642-1651.DOI:10.3748/wjg.v18.i14.1642.
[4]MOUCARI R,ASSELAH T,CAZALS-HATEM D,et al.Insulin resistance in chronic hepatitis C:association with genotypes 1 and 4,serum HCV RNA level,and liver fibrosis[J].Gastroenterology,2008,134(2):416-423.DOI:10.1053/j.gastro.2007.11.010.
[5]TRPKOVIC A,STOKIC E,RADAK D,et al.Chronic hepatitis C,insulin resistance and vascular disease[J].Curr Pharm Des,2010,16(34):3823-3829.
[6]FALLAHI P,FERRARI S M,COLACI M,et al.Hepatitis C virus infection and type 2 diabetes[J].Clin Ter,2013,164(5):e393-404.
[7]GARCIA-COMPEáND,GONZALEZ-GONZALEZJA,LAVALLE-GONZALEZ F J,et al.Current concepts in diabetes mellitus and chronic liver disease:clinical outcomes,hepatitis C virus association,and therapy[J].Dig Dis Sci,2016,61(2):371-380.DOI:10.1007/s10620-015-3907-2.
[8]IOVANESCU V F,STREBA C T,IONESCU M,et al.Diabetes mellitus and renal involvement in chronic viral liver disease[J].J Med Life,2015,8(4):483-487.
[9]SPRADLINGPR,SIMONSB,NARAYANANM,etal.Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection[J].J Viral Hepat,2013,20(7):510-513.DOI:10.1111/jvh.12071.
[10]NAINGC,MAKJW,AHMEDSI,etal.Relationship between hepatitis C virus infection and type 2 diabetes mellitus:metaanalysis[J].World J Gastroenterol,2012,18(14):1642-1651.DOI:10.3748/wjg.v18.i14.1642.
[11]ALI S A,NASSIF W M,ABDELAZIZ D H.Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes:a case-control study[J].Clin Res Hepatol Gastroenterol,2016,40(4):465-470.DOI:10.1016/j.clinre.2015.12.003.
[12]MEHTASH,BRANCATIFE,STRATHDEESA,etal.HepatitisCvirusinfectionandincidenttype2diabetes[J].Hepatolagy,2003,38(1):50-56.DOI:10.1053/jhep.2003.50291.
[13]LECUBEA,HEMANDEZC,GENESCAJ,etal.High prevalence of use abnormalities in patients with hepatitis C virus infection:a multivariate analysis considering the liver injury[J].Diabetes Care,2004,27(5):1171-1175.
[14]KAWAGUCHI T,YOSHIDA T,HARADA M,et al.Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3[J].Am J Pathol,2004,165(5):1499-1508.
[15]HICKMAN T J,POWELL E E,PRINS J B,et al.In overweight patients with chronic hepatitis C,circulating insulin is associated with hepatic fibrosis:implications for therapy[J].J Hepatol,2003,39(6):1042-1048.
[16]李光伟.胰岛素抵抗评估及其临床应用[J].中华老年多器官疾病杂志,2004,3(1):11-12.
[17]IKEDAY,SUEHIROT,NAKAMURAT,etal.Clinical significanceoftheinsulinresistanceindexasassessedby homeostasis model assessment[J].Endocr J,2001,48(1):81-86.
[18]GOUSTIN A S,ABOU-SAMRA A B.The"thrifty"gene encoding Ahsg/Fetuin-A meets the insulin receptor:insights into the mechanism of insulin resistance[J].Cell Signal,2011,23(6):980-990.DOI:10.1016/j.cellsig.2010.11.003.
[19]PESSIN J E,SALTIEL A R.Signaling pathways in insulin action:molecular targets of insulin resistance[J].J Clin Invest,2000,106(2):165-169.DOI:10.1172/JCI10582.
[20]GOUSTIN A S,DERAR N,ABOU-SAMRA A B.Ahsg-fetuin blocks the metabolic arm of insulin action through its interaction with the 95-kDβ-subunit of the insulin receptor[J].Cell Signal,2013,25(4):981-988.DOI:10.1016/j.cellsig.2012.12.011.
[21]陈婷,靳彦文,瞿秀华,等.胎球蛋白A的纯化及其对3T3-L1脂肪细胞胰岛素通路的抑制作用[J].解放军医学杂志,2010,35(7):819-822.CHEN T,JIN Y W,QU X H,et al.Purification of AHSG and its inhibition effect on insulin pathway of 3T3-L1 adipocyte[J].Med J Chin PLA,2010,35(7):819-822.
[22]张春梅,陈婷,李平,等.AHSG对胰岛素刺激下的HL-7702细胞中FAS、SREBP-1基因表达的影响[J].军事医学,2012,36(3):182-185,195.DOI:10.3969/j.issn.1674-9960.2012.03.005.ZHANG C M,CHEN T,LI P,et al.AHSG impact on expression of FAS and SREBP-1 genes of HL-7702 cells under insulin treatment[J].Military Medical Sciences,2012,36(3):182-185,195.DOI:10.3969/j.issn.1674-9960.2012.03.005.