非酒精性脂肪性肝病合并2型糖尿病患者血清同型半胱氨酸、成纤维细胞生长因子21和核因子-κB水平变化及其临床意义探讨

Implication of serum homocystein, fibroblast growth factor-21 and nuclear factor-κB levels in patients with non-alcoholic fatty liver diseases and T2DM

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者血清同型半胱氨酸(HCY)、成纤维细胞生长因子21(FGF21)和核因子-κB(NF-κB)水平变化及其临床意义。方法 2020年5月~2022年3月我院诊治的192例NAFLD和106例NAFLD合并T2DM患者【单纯性脂肪肝(SFL)76例,非酒精性脂肪性肝炎(NASH)21例,肝硬化9例】,采用ELISA法检测血清HCY、FGF21和NF-κB水平,使用FibroTouch行肝脏硬度检测(LSM)发现肝纤维化S0~S1期75例,S2~S4期31例。结果 NAFLD合并T2DM组血清低密度脂蛋白(LDL-C)、空腹血糖(FPG)和糖化血红蛋白(HbA1c)水平分别为(3.9±0.7)mmol/L、(8.6±1.3)mmol/L和(8.1±1.7)%,均显著高于NAFLD组【分别为(3.1±0.6)mmol/L、(5.2±1.1)mmol/L和(5.7±1.0)%,P<0.05】,而血清高密度脂蛋白胆固醇(HDL-C)水平为(1.0±0.2)mmol/L,显著低于NAFLD组【(1.4±0.2)mmol/L,P<0.05】;NAFLD合并T2DM组血清HCY、FGF21和NF-κB水平分别为(17.8±2.3)μmol/L、(315.2±32.5)pg/ml和(4.1±0.8)pg/mL,显著高于NAFLD组【分别为(14.1±1.9)μmol/L、(278.9±30.7)pg/ml和(2.8±0.5)pg/mL,P<0.05】;肝硬化患者血清HCY和NF-κB水平分别为(20.3±2.1)μmol/L和(5.0±1.0)pg/mL,显著高于NASH组【分别为(18.9±1.9)μmol/L和(4.5±0.7)pg/mL,P<0.05】或SFL组【分别为(16.2±1.6)μmol/L和(3.9±0.6)pg/mL,P<0.05】,而血清FGF21水平为(284.7±30.5)pg/ml,显著低于NASH组【(337.8±25.1)pg/ml,P<0.05】或SFL组【(312.5±28.3)pg/ml,P<0.05】;肝纤维化S2~S4期血清HCY和NF-κB水平分别为(20.9±1.8)μmol/L和(5.1±1.1)pg/mL,显著高于S0~S1期【(17.2±2.1)μmol/L和(3.9±0.8)pg/mL,P<0.05】,而血清FGF21水平为(291.1±26.7) pg/ml,显著低于S0~S1期【(319.8±28.3)pg/ml,P<0.05】。结论 NAFLD合并T2DM患者血清HCY、FGF21和NF-κB水平显著高于NAFLD患者,且这些指标与NAFLD临床分型和肝纤维化程度有关。

Objective The aim of this study was to explore the implication of serum homocystein(HCY), fibroblast growth factor-21(FGF21) and nuclear factor-κB(NF-κB) levels in patients with non-alcoholic fatty liver diseases(NAFLD) and type 2 diabetes mellitus(T2DM). Methods A total of 192 patients with NAFLD and 106 patients with NAFLD and T2DM were enrolled in our hospital between May 2020 and March 2022. Serum HCY, FGF-21 and NF-κB levels were detected by ELISA. The fasting plasma glucose(FPG) and glycosylated hemoglobin(HbA1c) were detected by glucose oxidase and high performance liquid chromatography, respectivley. The patients with NAFLD and T2DM were divided into simple fatty liver(SFL) in 76 cases, nonalcoholic steatohepatitis(NASH) in 21 cases and cirrhosis in 9 cases. All patients underwent liver stiffness measurement(LSM) by FibroTouch, and the liver fibrosis stage S0-S1 was found in 75 cases and stage S2-S4 in 31 cases. Results Serum LDL-C, FPG and HbA1c levels in patients with NAFLD and T2DM were(3.9±0.7)mmol/L,(8.6±1.3)mmol/L and(8.1±1.7)%, all significantly higher than [(3.1±0.6) mmol/L,(5.2±1.1)mmol/L and(5.7±1.0)%, P<0.05], while serum HDL-C level was(1.0±0.2)mmol/L, significantly lower than [(1.4±0.2)mmol/L, P<0.05] in patients with NAFLD;serum HCY, FGF21 and NF-κB levels in patients with NAFLD and T2DM were(17.8±2.3)μmol/L,(315.2±32.5) pg/ml and(4.1±0.8)pg/mL, significantly higher than [(14.1±1.9)μmol/L,(278.9±30.7)pg/ml and(2.8±0.5)pg/mL, respectively, P<0.05] in patients with NAFLD;serum HCY and NF-κB levels in patients with cirrhosis were(20.3±2.1)μmol/L and(5.0±1.0)pg/mL, both significantly higher than [(18.9±1.9)μmol/L and(4.5±0.7)pg/mL, P<0.05] in patients with NASH or [(16.2±1.6)μmol/L and(3.9±0.6)pg/mL, P<0.05] in patients with SFL, while serum FGF21 level was(284.7±30.5)pg/ml, significantly lower than [(337.8±25.1)pg/ml, P<0.05] in patients with NASH or [(312.5±28.3)pg/ml, P<0.05] in patients with SFL;serum HCY and NF-κB levels in patients with liver fibrosis staging S2-S4 were(20.9±1.8)μmol/L and(5.1±1.1)pg/mL, both significantly higher than [(17.2±2.1)μmol/L and(3.9±0.8)pg/mL, P<0.05] in patients with staging S0-S1, while serum FGF21 level was(291.1±26.7) pg/ml, significantly lower than [(319.8±28.3)pg/ml, P<0.05] in patients with staging S0-S1. Conclusion Serum HCY, FGF21 and NF-κB levels significantly increase in patients with NAFLD and T2DM, which might be related to clinical catalogues of NAFLD and the severity of liver fibrosis.