西格列汀联合二甲双胍治疗2型糖尿病合并NAFLD的疗效及其对患者糖脂代谢、肝功能、脂肪因子的影响

Efficacy of sitagliptin combined with metformin in the treatment of type 2 diabetes mellitus patients with nonalcoholic fatty liver disease and its effect on glucose and lipid metabolism,liver function,and adipokines

目的观察西格列汀联合二甲双胍治疗2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)患者的疗效,并探讨其对患者糖脂代谢、肝功能、脂肪因子的影响。方法选取2020年5月至2022年6月平顶山市第一人民医院收治的116例T2DM合并NAFLD患者作为研究对象,按随机数表法分为二甲双胍组和西格列汀联合组各58例。二甲双胍组患者予以二甲双胍治疗,西格列汀联合组患者在二甲双胍组治疗的基础上联合西格列汀治疗。治疗6个月后,比较两组患者的临床效果,以及治疗前后的糖脂代谢相关指标[空腹血糖(FPG)、糖化血红蛋白(HbA1c)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)]、肝功能相关指标[γ谷氨酰基转移酶(GGT)、天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)]水平、脂肪因子[血清趋化素(chemerin)、摄食抑制因子-1(nesfatin-1)水平]、体质量指数(BMI)、肝脏脂肪含量、CT肝脾密度比值、非酒精性脂肪性肝纤维化评分(NAFLDFS),并比较两组患者治疗期间的不良反应发生情况。结果治疗6个月后,西格列汀联合组患者的治疗总有效率为77.59%,明显高于二甲双胍组的60.34%,差异有统计学意义(P<0.05);治疗6个月后,西格列汀联合组患者的HbA1c、FPG、LDL-C水平、血清GGT、AST、ALT、chemerin、nesfatin-1水平、BMI、肝脏脂肪含量、NAFLDFS评分分别为(6.69±0.64)%、(6.87±0.76)mmol/L、(2.49±0.30)mmol/L、(41.78±2.71)U/L、(34.09±2.38)U/L、(35.75±2.09)U/L、(72.49±10.73)ng/mL、(5.70±1.85)ng/mL、(25.37±0.95)kg/m^(2)、(8.27±1.28)%、(0.32±0.06)分,明显低于二甲双胍组的(7.24±0.78)%、(7.46±0.82)mmol/L、(2.84±0.41)mmol/L、(46.47±3.35)U/L、(38.12±3.26)U/L、(39.52±2.63)U/L、(80.51±12.09)ng/mL、(6.62±2.09)ng/mL、(26.18±1.02)kg/m^(2)、(9.41±1.56)%、(0.47±0.08)分,HDL-C水平、CT肝脾密度比值分别为(1.92±0.68)mmol/L、0.93±0.08,明显高于二甲双胍组的(1.57±0.59)mmol/L、0.81±0.12,差异均有统计学意义(P<0.05);治疗期间,西格列汀联合组患者的不良反应发生率为12.07%,略高于二甲双胍组的8.62%,但差异无统计学意义(P>0.05)。结论西格列汀联合二甲双胍治疗T2DM合并NAFLD患者临床疗效较好,可有效改善糖脂代谢和肝功能指标,降低BMI、肝脏脂肪含量、脂肪肝与肝纤维化程度,并下调血清chemerin、nesfatin-1水平,具有较高的安全性。

Objective To observe the efficacy of sitagliptin combined with metformin in treatment of type 2 di-abetes mellitus(T2DM)patients with nonalcoholic fatty liver disease(NAFLD),and to explore its effects on glucose and lipid metabolism,liver function,and adipokines.Methods A total of 116 patients with T2DM and NAFLD admitted to Pingdingshan First People's Hospital from May 2020 to June 2022 were collected as research objects and randomly di-vided into metformin group and sitagliptin combined with metformin group by random number table,with 58 patients in each group.The metformin group was treated with metformin,while the sitagliptin combined with metformin group was treated with sitagliptin on the basis of the metformin group.After 6 months of treatment,the clinical effects,glucose and lipid metabolism indicators[glycosylated hemoglobin A1c(HbA1c),fasting plasma glucose(FPG),low density lipopro-tein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)],and liver function indicators[γ-glutamyltrans-ferase(GGT),aspartate aminotransferase(AST),alanine aminotransferase(ALT)],adipose factors[serum levels of chemo-kine,dietary inhibitor-1(nesfatin-1)],body mass index(BMI),liver fat content,CT liver spleen density ratio,and nonalco-holic fatty liver fibrosis score(NAFLDFS)before and after treatment were compared between the two groups.The inci-dence of adverse reactions was compared between the two groups during the treatment.Results After 6 months of treat-ment,the total effective rate in the sitagliptin combined with metformin group was 77.59%,which was significantly higher than 60.34%in the metformin group(P<0.05).After 6 months of treatment,the levels of HbA1c,FPG,LDL-C,serum lev-els of GGT,AST,ALT,chemerin,nesfatin-1,BMI,liver fat content,and NAFLDFS in sitagliptin combined with metfor-min group were(6.69±0.64)%,(6.87±0.76)mmol/L,(2.49±0.30)mmol/L,(41.78±2.71)U/L,(34.09±2.38)U/L,(35.75±2.09)U/L,(72.49±10.73)ng/mL,(5.70±1.85)ng/mL,(25.37±0.95)kg/m2,(8.27±1.28)%,and(0.32±0.06)points,respec-tively,which were significantly lower than(7.24±0.78)%,(7.46±0.82)mmol/L,(2.84±0.41)mmol/L,(46.47±3.35)U/L,(38.12±3.26)U/L,(39.52±2.63)U/L,(80.51±12.09)ng/mL,(6.62±2.09)ng/mL,(26.18±1.02)kg/m2,(9.41±1.56)%,and(0.47±0.08)points in the metformin group;the HDL-C level and CT liver spleen density ratio were(1.92±0.68)mmol/L and 0.93±0.08,respectively,which were significantly higher than(1.57±0.59)mmol/L and 0.81±0.12 in the metformin group;the differences were statistically significant(P<0.05).During the treatment,the incidence of adverse reactions in the sitagliptin combined with metformin group was 12.07%,which was slightly higher than 8.62%in the metformin group(P>0.05).Conclusion Sitagliptin combined with metformin in the treatment of patients with T2DM and NAFLD can effectively improve glucose and lipid metabolism and liver function,reduce BMI,liver fat content,fatty liv-er,and liver fibrosis,and down-regulate serum levels of chemerin and nesfatin-1,with high safety.