非酒精性脂肪肝患者血清肿瘤坏死因子-α、脂联素水平与胰岛素抵抗的相关性

Pilot study correlating tumor necrosis factor-α,adiponectin and insulin resistance in patients with non-alcoholic fatty liver

目的:探讨非酒精性脂肪肝(NAFLD)患者肿瘤坏死因子-α、脂联素水平与胰岛素抵抗等指标的相互关系.方法:120例NAFLD患者根据空腹血糖水平分为合并2型糖尿病(T2DM)者32例(DFL组),不伴T2DM者88例(FL组),所有NAFLD患者根据B超结果分为轻度、中度、重度3组.测定NAFLD患者及42例健康对照者的体质量指数(BMI)、腰臀比(WHR)、空腹血糖(FPG)、空腹胰岛素(FINS)、肿瘤坏死因子-α(TNF-α)、脂联素(APN)水平;采用稳态模式计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(ISI)、反应胰岛β细胞分泌功能的指标(HOMA-IS)等指标.结果:NAFLD患者的FINS,HOMA-IR均显著升高,ISI显著低于NC组(P<0.01);FPG,FINS,ISI,HOMA-IS是IR抵抗的主要相关因素;DFL组的FINS,HOMA-IR较FL组为高,ISI,HOMA-IS较FL组为低,均有显著性差异(P<0.01);NAFLD患者轻、中度两组间HOMA-IR无显著差异(P>0.05),而重度脂肪肝患者的HOMA-IR明显升高(P<0.01).NAFLD患者血清TNF-α显著升高,APN显著降低(P<0.01);APN与TNF-α,IR呈显著负相关,与ISI呈显著正相关;TNF-α是影响APN水平的重要因素;TNF-α与APN,ISI呈显著负相关,与FPG,FINS,IR呈显著正相关,ISI,APN是其主要的影响因素.结论:NAFLD患者普遍存在IR,合并2型糖尿病的NAFLD患者体内胰岛素抵抗现象更为明显;TNF-α与APN呈显著负相关,且均与IR密切相关.APN作为保护性因子而TNF-α作为损害性因子在NAFLD的发生、发展中起着重要作用.

AIM： To measure serum tumor necrosis factor （TNF）-α and adiponectin （APN） levels in patients with non-alcoholic fatty liver disease （NAFLD）, and to explore the relationship between this and insulin resistance. METHODS： Forty-two normal controls （NCs） and 120 patients with NAFLD were recruited, According to fasting plasma glucose （FPG）, patients were divided into a group with NAFLD and type 2 diabetes （DFL; n = 32） and a simple NAFLD group （FL; n = 88）. All patients with NAFLD were divided into mild （n = 59）, moderate （n = 37） and severe （n = 24） categories, ac- cording to the results of B type ultrasound. Body mass index （BMI）, waist-to-hip ratio （WHR）, FPG, fasting insulin level in serum （FINS）, serum APN and TNF-α were measured. Homeo- stasis model assessment （HOMA）, insulin sensitive index （ISI） and insulin secretion （HOMA-IS） were applied to the status of insulin resistance （IR）. Correlation analysis among these factors was analyzed. RESULTS： Compared with the NC group, FINS and HOMA-IR levels in the DFL and FL groups were significantly increased, and ISI was signifi- cantly decreased （all P 〈 0.01）. Compared with the FL group, FINS and HOMA-IR levels in the DFL group were significantly increased, and ISI and HOMA-IS were significantly decreased （all P 〈 0.01）. The difference in HOMA-IR level was not significantly different between the mild and moderate NAFLD groups （P 〉 0.05）, which were both lower than the severe group （all P 〈 0.01）. TNF-α level in the DFL and FL groups was significantly higher, while serum APN was significantly lower than that in the NC group （P 〈 0.01）. Correlation analysis showed that APN was significantly negatively correlated with HOMA-IR and TNF-α, and positively correlated with ISI. TNF-α was significantly negatively correlated with APN and ISI, and positively correlated with FPG, FINS and IR. Multiple stepwise regression analysis showed that BMI, FPG, FINS and TNF-α were the main risk factors for IR. ISI and APN were the main risk factors for TNF-α. TNF-α was the main risk factor for APN. CONCLUSION： Insulin resistance is uniformly present in subjects with NAFLD and is more obvious in patients with type 2 diabetes. There is a significant negative correlation between APN and TNF-α, and both have close correlations with IR. APN has a protective role, while TNF-α causes impairment, and both have important roles in the pathogenesis and progression of NAFLD.