非酒精性脂肪肝患者血浆FGF21水平及与肥胖、胰岛素抵抗关系研究

Correlation between plasma fibroblast growth factor 21 level,obesity and insulin resistance in nonalcoholic fatty liver disease patients

目的探讨非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)患者血浆成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)水平及与肥胖、胰岛素抵抗等因素的相关性。方法根据是否合并糖尿病将70例NAFLD患者分为单纯脂肪肝组36例和2型糖尿病合并脂肪肝组34例,正常对照组26例,采用酶联免疫分析法检测血浆FGF21水平,并测定空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting insulin,FINS)、游离脂肪酸(free fattyacids,FFA)、血脂水平,以及体质量指数(body mass index,BMI)、腰臀比(waist-to-hipratio,WHR);采用稳态模型HOMA-IR和胰岛素敏感指数(insulin sensitivity index,ISI)评价胰岛素抵抗状态。结果①2组脂肪肝患者中,肥胖比例、BMI及WHR均显著高于正常对照组,甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(lowdensity lipoprotein cholesterol,LDL-C)、FFA显著增高(P<0.05,P<0.01),高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)降低(P<0.05);糖尿病合并脂肪肝组HOMA-IR明显增高(P<0.01),ISI显著降低(P<0.05)。②单纯脂肪肝和糖尿病合并脂肪肝患者血浆FGF21水平[(1.86±0.64)、(1.97±0.60)ng/ml]明显高于健康对照组[(1.26±0.43)ng/ml,P<0.05]。③相关分析显示:血浆FGF21水平与BMI、WHR、HOMA-IR、TG、FFA呈正相关(r=0.278、0.335、0.326、0.312、0.307,P<0.05,P<0.01),与HDL、ISI呈负相关(r=-0.255、-0.279,P<0.05)。④多元逐步回归分析显示:WHR、HOMA-IR、TG是血浆FGF21的独立相关因素。结论NAFLD患者血浆FGF21水平升高,FGF21与肥胖、胰岛素抵抗、脂代谢紊乱有关,FGF21可能在脂肪肝的发生、发展中起了一定的作用。

Objective To investigate the correlation between plasma fibroblast growth factor 21 （FGF21） level, obesity and insulin resistance （IR） in nonalcoholic fatty liver disease （NAFLD） patients. Methods Seventy NAFLD patients were divided into fatty liver （FL） group （ n = 36）, type 2 diabetes complicated by fatty liver （DFL） group （ n = 34 cases）, and normal control （NC） group （ n = 26） according to their complication of type 2 diabetics. Levels of plasma FGF21, fasting plasma glucose （FPG） , fasting insulin （FINS）, free fatty acid （FFA）, lipid, body mass index （BMI） and waist-to-hip ratio （WHR） were measured by enzyme-linked immunosorbent assay. Insulin resistance was evaluated using the steady-state model HOMA- IR and insulin sensitivity index （ISI）. Results The levels of obesity, BMI, WHR, triglyceride （TG）, total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C）, and FFA were significantly higher in FL and type 2 DFL groups than in NC group（P 〈0.05, P 〈0.01 ）. The high-density lipoprotein cholesterol （HDL-C） level was lower in FL and type 2 DFL groups than in NC group （ P 〈 0.05 ）. The HAMO-IR was significantly higher and ISI was notably lower in type 2 DFL group than in NC group（P 〈0.01, 0.05）. The plasma FGF21 level was significantly higher in FL and type 2 DFL groups （ 1.86 ± 0. 64） ng/ml and （ 1.97 ± 0. 60） ng/ml than in NC group （1.26± 0. 43 ） ng/ml （P 〈 0.05 ）. Correlation analysis showed that the plasma FGF21 level was positively correlated with BMI, WHR, HOMA-IR, TG, and FFA（r =0.278, 0.335, 0. 326, O. 312, and 0. 307 ）, respectively （ P 〈 0.05 or P 〈 0.01 ）, and negatively correlated with HDL and ISI （ r = - 0. 255, -0. 279）, respectively （P 〈 0.05 ）. Multiple stepwise regression analysis indicated that WHR, HOMA-IR and TG were the independently relevant factors for serum FGF21 level. Conclusion Elevated plasma FGF21 level in NAFLD patients is closely related with obesity, insulin resistance and lipid metabolism disorder, and may play a role in the occurrence and development of FL.