福州地区非酒精性脂肪肝的流行病学调查及游离脂肪酸在非酒精性脂肪肝病发病中的意义
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:通过对福州城区进行非酒精性脂肪肝(Non-alcoholic Fatty Liver Disease,NAFLD)的流行病学调查,分析福州地区NAFLD的危险因素及患病率;初探游离脂肪酸(Free fatty acids, FFA)在NAFLD发病中的意义,探讨NAFLD患者中胰岛素抵抗与FFA的关系,为NAFLD的发病机制和防治提供新的理论依据。
     方法:第一部分采用随机多级分层整群抽样的方法对福州地区2条街道16岁以上居民进行调查。内容包括问卷、体格检查、生化检查、肝脏彩超检查;第二部分采用病例对照方法选出NAFLD组和对照组,除了前面的内容,还用ELISA法测血清胰岛素(Insulin,INS)、FFA,。
     结果:2850名居民接受了完整调查,此次调查对象约占福州城区人口的17.59/10000人。研究对象中男性1350人,女性(不包括孕妇)1500人,男女之比为1:1.11。年龄16~82岁,平均(52.40±16.20)岁,男女间年龄差异无统计学意义。彩超共检出脂肪肝729例,占25.58%,其中酒精性脂肪肝、可疑酒精性脂肪肝、NAFLD患病率分别占17.28%、3.43%、79.29%。经过性别、年龄调整后,脂肪肝患病率为25.58%,故NAFLD、酒精性脂肪肝、可疑酒精性脂肪肝的患病率分别为20.28%、4.42%、0.88%。NAFLD患病率随年龄增长而增加,55岁以前男性NAFLD患病率显著高于女性,χ2=25.708,P<0.001;而55岁后女性脂肪肝患病率显著高于男性,χ2=4.320,P<0.05。NAFLD组体重指数(Body mass index, BMI)、腰围、血压、空腹血糖(Fasting blood glucose, FBG)、甘油三酯(Triglycerides, TG)、总胆固醇(Total cholesterol, TC)、低密度脂蛋白胆固醇(Light density lipoprotein-cholesterol, LDL-C)显著高于非脂肪肝组(所有P<0.001),高密度脂蛋白胆固醇(High density lipoprotein-Cholesterol, HDL-C)水平显著低于非脂肪肝组(P<0.001);肥胖、糖尿病、高血压病、血脂异常和肝功能异常发生率均显著高于非脂肪肝组(所有P<0.001)。二分类变量Logistic回归分析显示:腰围、BMI、HDL-C、TG、FBG、腰臀比(Waist hip ratio,WHR)、糖尿病、高血压病、肝功能异常等9项因子与NAFLD密切相关。NAFLD患者中FFA水平高于正常对照组(P<0.01),差异有统计学意义。NAFLD患者中FFA水平与胰岛素敏感度(Insulin sensitivity index,ISI)呈显著负相关,FFA水平与胰岛素抵抗密切相关。
     结论:1、福州城区脂肪肝的患病率为25.58%,其中以NAFLD(20.28%)为主。2、高血压病、2型糖尿病、肝功能异常、FBG、WHR、TG、BMI及腰围与NAFLD呈正相关,是其危险因素;HDL-C与NAFLD呈负相关,是其保护因素。3、FFA与NAFLD密切相关, NAFLD患者中IR与FFA呈负相关。
Objective To investigate the prevalence and major risk factors of non-alcoholic fatty liver(NAFLD) among adult residents in Fuzhou, explore the role of free fatty acids in NAFLD and the relationship between insulin resistance and the free fatty liver(FFA) in NAFLD patients, and provide the new theory for the pathogenesis and prevention of NAFLD.
     Methods In first part, a cross-sectional survey with multiple-stage stratified cluster and random sampling was performed. All residents aged 16 years and above were invited to participate in the survey; they came from 2 streets of Fuzhou. Ques-tionnaire, physical examination, serum lipid-profile, 75 gram oral glucose tolerance test, and ultrasonographic examination of liver were undertaken; in second part, case-control study was perfoemed, NAFLD and conctol group, all the above were undertaken, also including serum insulin, FFA by ELISA. Analysis of data was performed by SPSS13.0 for Windows statistical package.
     Results A total of 2850 adult residents took part in the survey,which was 87.31% of residents of the investigated communities and 17.59/10000 of Fuzhou municipal residents. Of the 2850, 1350 were males and 1500 were females. The mean age of the participants was 52.40±16.20 years and ranged from 16~82 years. Fatty liver was detected with ultrasound examination in 729 participants(25.58%),among which 17.28% had alcoholic fatty liver, 3.43% had suspected alcoholic fatty liver, and 79.29% had NAFLD.The age-adjusted, sex-adjusted prevalence of fatty liver in Fuzhou residents was 25.58%, the prevalence of alcoholic fatty liver,suspicious alcoholic fatty liver,and NAFLD in Fuzhou residents were 4.42%, 0.88%, and 20.28% respectively. The prevalence of NAFLD was increased with aging in males and in females.Among participants younger than 55 years,the prevalence of NAFLD in males was significantly higher than that in females(χ2= 25.708, P<0.001), but in participants older than 55 years the case was just the opposite, higher in females(χ2= 4.320, P<0.05). The body mass index(BMI), waist circumference, blood pressure, fasting blood glucose level, triglyceride(TG), Total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and the incidence of obesity, diabetes2 mellitus, hypertension, dyslipidemia in NAFLD group were significantly higher than those in the group without fatty liver(all P<0.001), but the high-density lipoprotein cholesterol(HDL-C) level was lower in NAFLD group (P<0.001). Logistic regression analysis demonstrated that the prevalence of fatty liver was only closely correlated to nine factors, including waist circumference, WHR, BMI, FBG, TG, hypertension, abnormal hepatic function and diabetes mellitus. The level of FFA in NAFLD patients was higher than that of the control group, P<0.01, the difference was statistically significant. In NAFLD patients FFA levels was significantly negatively correlated with insulin sensitivity index(ISI), the level of FFA was positively related to insulin resistance.
     Conclusion 1. The prevalence of fatty liver among residents in Fuzhou is 25.58%, and NAFLD(20.28%) is the major type. 2.The hypertension, type 2 diabetes, TG, waist circumference, BMI, FBG, WHR and abnormal hepatic function are positively related to NAFLD,which are risk factors; HDL-C is negatively correlated with NAFLD,which is protective factor; 3. FFA concentration is closely associated with NAFLD, in NAFLD patients FFA is positively related to IR.
引文
1.Medina J, Femandez-Salazar LI, Garcia-Buey L, et al. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis〔J〕. Diabetes Care,2004, 27: 2057- 2066.
    2.范建高,朱军,李新建等.上海市成人脂肪肝患病率及其危险因素流行病学调查[J].中华肝脏病杂志,2005,13(2):83-86.
    3.Day C P, Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut, May 2002;50: 585–588.
    4. 范 建 高 . 非 酒 精 性 脂 肪 肝 的 临 床 流 行 病 学 研 究 [J]. 中 华 消 化 杂志,2002 ,22(2):106-107.
    5.李葳,江倔,夏国光,等.脂肪肝高脂血症的年龄性别因素与胰岛素抵抗的关系探讨[J].中国全科医学杂志,2000,3(5):355-356.
    6.何江,王建英,汪伟伟,等.不同职业人群脂肪肝流行病学调查研究[J].中华流行病学杂志,1999,20(3):169-169.
    7.卢和.45 岁以上中老年人脂肪肝患病情况分析[J].临床内科杂志,2000, 17(2):95-96.
    8.Kumar KS ,Malet PF.Nonalcoholic steatohepatitis[J].Mayo Clin Proc,2000,75(7):733-739.
    9.Rashid M,Roberts ER. Nonalcoholic steatohepatitis in child[J] . J Pediatr Gastroenterol Nutr,2000,30(1):48-53.
    10.Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001,121:91–100.
    11.Crespo J,Fernandez-Gil P,Hernandez-Guerra M,et al.Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis? Obes Surg.2001;11:254-7.
    12.Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg. 2002,12:49–51.
    13.高爱滨,肖谦,高原,苗菁等.重庆市公务员非酒精性脂肪肝患病率及危险因素分析[J].中国慢性病预防与控制,2007,15(1):22-25.
    14.Choudhury J, Samyal AJ,Lusulin resistance and the pathogenesis of nonalcoholic fay liver disease Clin Liver Dis,2004,8:575-594.
    15.Diehl AM. Fatty liver,hypertension , and the metabolic syndrome[J].Gut, 2004,53:923-924.
    16.毛腾淑,路影,胡肇衡,等.Ⅱ型糖尿病人的胰岛素抵抗与动态血压的关系[J].北京医科大学学报,1997,29:516-518.
    17.袁和顺.高血压与相关疾病的调查分析[J].实用预防医学,2002,9(5):547.
    18.彭健.高血压与血脂代谢紊乱[J].中国实用内科杂志,2002,22(4):202.
    19. 陈 文 瑞 . 原 发 性 高 血 压 与 代 谢 异 常 相 关 分 析 [J]. 实 用 临 床 医学,2001,2(3):112-113.
    20. 李 淑 彩 . 高 血 压 与 高 血 脂 高 血 糖 脂 肪 肝 的 关 系 [J]. 中 国 校医,2004,18(5):443.
    21.陆 奇,李一平,杨家珍,等.老年收缩期高血压患者血脂、血糖及胰岛素水平的测定[J].中华老年医学杂志,1999,18(2):97-101.
    22.Seppala-Lindroos A,Vehkavaara S,Hakkinen A-M.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 [J].J Clin Endocrinol metab,2002,87:3023-3028.
    23.林小荣,林广玲,冯欣衡,等.脂肪肝与高脂血症的关系探讨[J].现代医院2006,6(6):64-65.
    24.路 萍,赵春颖,刘 霞.高脂血症与脂肪肝患病率分析[J].齐齐哈尔医学报, 2000,2(1):68.
    25.Clark JM, Brancati FL, and Diehl AM. Nonalcoholic fatty liver disease: the most common cause of abnormal liver enzymes in the U.S. population. Gastroenterology. 2001;120(Suppl 1):A-65.
    26.Clark JM, Brancati FL, Diehl AM.Nonalcoholic fatty liver disease. Gastroe- nterology.2002;122:1649–57.
    27.Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98:960–7.
    28.Silverman JF, O’brien KF, Long S, et al. Liver pathology in morbidly obese patients with and without diabetes. Gastroenterol, 1990, 85: 1349-1355.
    29.Marchesim C,BriziM,Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic Syndrome.Diabetes,2001,50:1844-1850.
    30.James O,Day C.Nonalcoholic steatohepatitis:another diasease of affluence[J]. Lancet,1999,353(9165):1634-1636.
    31.Randle PJ,Garland PB,Hales CN,et a1.The glucose fatty acid cycle:its role in insulin sensitivity and metabolic disturbance of diabetes mellitus[J].Lancet.1963,1:785~789.
    32.Kelley DE,Kuller LH,McKolanis TM et a1.Efects of moderate weight loss and orlistat on insulin resistance,regional adiposity,and fatty acids in type 2 diabetes[J].Diabetes Care,2004,7(1):33-40.
    33.Vettor R ,Lombardi AM ,Fabris R ,et al. Substrate competition and insulin action in animal models. Int J Obes Relat Metab Disord ,2000 ,24(suppl) 2 :s22-24.
    34.Griffin ME ,Marcucci MJ ,Cline GW,et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase Cθ and alterations in the insulin signaling Cascade.Diabetes,1999,48:1270-1274.
    1 Day C P, Non-alcoholic Steatohepatitis (NASH): where are we now and where are we going?[J].Gut, May 2002;50: 585-588.
    2 Marchesini G,Bugianesi E,Forlani G, et al. Non-alcoholic fatty liver,steatohepatitis, and the metabolic syndrome[J]. Hepatol,2003;37:917–23.
    3 Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Non-alcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities[J]. Gastroenterol, 2001;120:1183-92.
    4 Newgard CB,McGarry D.Metabolic coupling factors in pancreatic β-cell signal transduction[J].Annu Ren Biochem,1995,64:689-719.
    5 Kida V,Nyomba B L,Bogardus C,et a1.Defective insulin response of cyclic adenosine monophosphat dependent protein kinase in insulin resistant humans [J].Clin Invest,1991,87:673-679.
    6 Zeme1 MB.Nutritional and endocrine modu1ation 0f intracellu1ar calcium: implications in obesity,insulin resistance and hypertension[J].Mol Cell Biochem, l998,188(1-2):129-136.
    7 Jang YJ,Ryu HJ,Choi Y0,et a1.Improvement of insulin sensitivity by chelation of intracellular Ca2+ in high-fat-fed rats[J].Metabolism,2002:51(7):9l2-918.
    8 Xue BZ,Wilkison WO,Mynatt RI,et al .The agouti gene product stimulates pancreatic β-cell Ca2+ signaling and insulin release[J].Physiol Genoraics, l999 , l(1):l1-19.
    9 Missianenl,Robbrecht W,Vanden Bosch L,et a1.Abnormal Intracelhlar(Ca2+ ) homeostasis and disease[J].Cell Calcium,2002:28(1):1-21.
    10 Barbagallo M,Gupta P K,Resnick L M.Cellularions in NIDDM :relation of calcium to hyperglycemia and cardiac mass [J].Diabetes Care,1996,19:1393.
    11 Reid AE. Non-alcoholic steatohepatitis[J]. Gastroenterology,2001,121: 710-723.
    12 Wang SY,CLagee JR,Langer GA.Increase in calcium leak channel Activity by metaboilc inhibition on hydrogen peroxide in rat ventricular myocytes and its inhibition by polycation [J].Mol Cell Cardiol,l995;27:2l1-2l6.
    13 Ungvan E,Koller A Endothelin and prostaglandin H2/thromboxane A2 enhancemyogenic constriction in hypertension by increasing Ca2+ sensitivity of arteriolar smooth muscle [J].Hypertension,2000;36(5):856-861.
    14 Vau Tits I J,Hak-Lemmers HI ,Demacker PN,et a1.Oxidized low-density lipoprotein induces calcium influx in polymorphonuclear leukoeytes[J].Free Radic Bio1 Med,2O00,29(8):747-755.
    15 Zemel MB,Miller SL.Dietary calcium and dairy modulation of adiposity and obesity risk[J].Nutr Rev,2004,62(4):125-131.
    16 Zemel MB.Calcium modulation of hypertension and obesity.mechanisms andimplicate-ons[J].J Am Coll Nutr,200l,20[5 Suppl]:428S-435S.
    17 Zemel Michael B.Regulation of adiposity and obesity risk by dietary calcium:mechanism and implications[J].The American College of Nutrition,2002 21(2):146S-151S.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700