2型糖尿病伴非酒精性脂肪肝病患者血清二肽基肽酶-4水平与外周单核细胞M1/M2失衡的关系

Relationship between serum DPP-4 level and M1/M2 imbalance of peripheral monocytes in type 2 diabetes mellitus combined with NAFLD patients

目的分析初发2型糖尿病伴非酒精性脂肪肝病(NAFLD)患者血清DPP-4水平与外周单核细胞M1/M2失衡的关系,探讨血清DPP-4对慢性低度炎症及胰岛素抵抗、糖脂代谢的影响。方法选取2019年1月至2019年6月在我院内分泌科门诊及住院初次诊断2型糖尿病患者,总病例数70例,根据其是否合并非酒精性脂肪肝分为2型糖尿病组(T2DM组)36例和2型糖尿病合并NAFLD组(T2DM+NAFLD组)34例。测量所有患者身高、体质量、并计算体质量指数(BMI);检测肝功能、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)与低密度脂蛋白胆固醇(LDL-C)、空腹胰岛素(FINS)及糖化血红蛋白(HbA1c),并计算胰岛素抵抗指数(HOMA-IR);酶联免疫吸附试验(ELISA)方法检测血清二肽基肽酶-4(DPP-4)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6及IL-10;采用实时荧光定量(Real-time)PCR法检测人血外周单核细胞TNF-α、IL-6及IL-10mRNA表达。结果与T2DM组比较,T2DM+NAFLD组BMI、HBA1c、FINS、AST、TG水平显著增高(P<0.05);且T2DM+NAFLD组血清促炎因子TNF-α、IL-6水平明显升高,而抗炎因子IL-10明显下降(P<0.05);脂肪因子DPP-4水平显著高于T2DM组(P<0.05);Pearson相关性分析显示血清DPP4水平与BMI、HBA1c、HOMA-IR、ALT、TG、TNF-α、IL-6呈正相关,与IL-10呈负相关;与外周血单核细胞炎症因子TNF-α、IL-6mRNA表达呈正相关,与IL-10mRNA表达呈负相关。结论对T2DM+NAFLD人群而言,其血清DPP4水平与外周单核细胞M1/M2失衡继发的促炎/抗炎因子表达异常有关,推断由此产生的慢性低度炎症加重了外周胰岛素抵抗及糖脂代谢紊乱。

Objective To analyze the relationship between serum DPP-4 level and M1/M2 imbalance of peripheral monocytes in newly diagnosed type 2 diabetes mellitus patients with NAFLD,and to explore the effects of serum DPP-4 on chronic low-grade inflammation,insulin resistance,glucose and lipid metabolism.Methods A total of 70 patients with type 2 diabetes who were diagnosed in the Department of endocrinology of our hospital from January 2019 to June 2019 for the first time were enrolled and divided into type 2 diabetes group(T2DM group/36 cases)and type 2 diabetes mellitus combined with nonalcoholic fatty liver disease group(T2DM+NAFLD group/34 cases)according to whether they were combined with nonalcoholic fatty liver disease.The height,weight and BMI of all patients were measured;liver function,total cholesterol(TC),triglyceride(TG),high density protein cholesterol(HDL-C),low density protein cholesterol(LDL-C),fasting insulin(fins)and HbA1c were detected,and HOMA-IR was calculated;serum DPP-4,TNF-α,IL-6 and IL-10 were detected by ELISA;real-time PCR was used to detect the expression of TNF-α,IL-6 and IL-10 mRNA in human peripheral monocytes was measured.Results Compared with T2DM group,the levels of BMI,HbA1c,fins,AST,ALT and TG in T2DM+NAFLD group were significantly increased(P<0.05);the levels of serum pro-inflammatory factors TNF-αand IL-6 were significantly increased in T2DM+NAFLD group,while the anti-inflammatory factor IL-10 was significantly decreased(P<0.05);the level of fat factor DPP-4 was significantly higher than that of T2DM group(P<0.05);the level of DPP-4 was positively correlated with BMI,serum TG,HBA1c,ALT,TNF-α,IL-6 and HOMA-IR.It was negatively correlated with and IL-10,positively correlated with TNF-αand IL-6 mRNA expression in peripheral blood mononuclear cells,and negatively correlated with IL-10 mRNA expression.Conclusion For T2DM+NAFLD population,the serum DPP4 level is related to the abnormal expression of pro-inflammatory/anti-inflammatory factors induced by the imbalance of M1/M2 of peripheral monocytes.It is in-ferred that the chronic low-grade inflammation caused by this may aggravate the peripheral insulin resistance and the disorder of glucose and lipid metabolism.