Research On The Relationship Between Liver Fibrosis And Insulin Resistance In Patients Combined With Type 2 Diabetes Mellitus And Nonalcoholic Fatty Liver Disease

Objective In this study,patients with type 2 diabetes(T2DM)combined with non-alcoholic fatty liver disease(NAFLD)as the main subjects to explore the relationship between liver fibrosis and insulin resistance(IR),and to analyze other risk factors that may affect the progression of liver fibrosis.Methods A total of 484 patients with T2DM who met the inclusion and exclusion criteria and were admitted to the Special Needs Internal Medicine Department of The Second Hospital of Lanzhou University from December 2018 to July 2020 were collected.According to the results of abdominal ultrasound,107 patients were divided into the simple T2DM group,and 377 patients were divided into the T2DM combined with NAFLD group.Medical history data including gender,age and course of T2DM were captured,body weight and height were measured,and body mass index(BMI)was counted.Inspection result such as glycosylated hemoglobin(HbA1c),aspertate aminotransferase(AST),alanine aminotransferase(ALT),AST/ALT,triglyceride(TG),total cholesterol(CHO),high-density lipoprotein(HDL),low density lipoprotein(LDL),albumin(propagated),blood uric acid(UA),platelet(PLT)were gathered;The standard steamed bread meal test was completed,and fasting blood glucose(FPG),fasting insulin(FINS),fasting C peptide(FCP),and Postprandial Blood Glucose and insulin were recorded at each time point,and the systolic and diastolic blood pressure of brachial artery were taken after a 30min break;IR degree indicators were calculated,such as ① Homeostasis model assessment insulin resistance index(HOMA-IR)②Insulin sensitivity assessment index(ISImatsuda)③Insulin sensitivity index(ISI)④steamed buns postprandial area under insulin curve/area under blood glucose curve(AUCI/AUCG)and NAFLD fibrosis score(NFS)of patients with NAFLD.Then,NFS was used as the severe liver fibrosis hierarchy standard,incorporating T2DM patients with NAFLD group is divided into three subgroups,namely the NFS<1.455 for the exclusion of liver fibrosis subgroups(T2DM+F0,136 cases),1.455≤NFS<0.676 for uncertain subgroups(T2DM+F1,146 cases),NFS≥0.676 for fibrosis subgroups(T2DM+F2,95 cases),comparing the IR degree between subgroups,explore the relationship between IR and liver fibrosis.SPSS25.0 statistical software was used for data analysis.The Logistic regression analysis was used to analyze the independent risk factors for liver fibrosis in T2DM combined with NAFLD patients.Pearson correlation analysis was used to analyze the relationship between NFS and various IR indicators.ROC curve was used to evaluate the value of different IR applications in the diagnosis of liver fibrosis,the standard for statistically significant difference was P<0.05.Results 1.The general results:compared with the simple T2DM group,the IR indexes and biochemical data of the T2DM combined with NAFLD was found that except HOMA-IR(9.08(5.84～12.09)VS 2.52(1.30～4.91)),AUCI/AUCG(2.86(1.62～4.13)VS 1.85(0.93～3.44))elevated,BMI,AST,ALT,FPG,HbAlc,FCP,FINS,UA,CHO,TG and blood pressure increased at different degrees also,while the ISImatsuda(32.07(23.97～45.86)VS 89.31(59.11～160.56))and ISI(0.005(0.004～0.008)VS 0.018(0.009～0.034))、PLT decreased.the differences were statistically significant(P<0.05).2.Study on the relationship between IR and hepatic fibrosis of T2DM complicated with NAFLD:Patients with T2DM complicated with NAFLD were divided into three subgroups,in which the fibrosis subgroup(T2DM+F2)accounted for 25.20%.The HOMA-IR of the T2DM+F0 group,T2DM+F1 group and T2DM+F2 group were 6.21±2.99,9.74±4.16,11.96±4.66,respectively,ISImatsuda:45.61(32.55～68.60),29.59(22.31～38.11),27.33(22.32～36.85),ISI:0.007(0.005～0.120),0.005(0.004～0.006),0.004(0.003～0.005),with statistically significant differences(P<0.05).Take fibrosis severity level as the dependent variable,multivariate logistic regression analysis was performed,the result shows:after adjustment for other factors such as gender,age,course,BMI,AST,AST/ALT,ALB,PLT,CHO,SBP,HOMA-IR(β=0.236,OR=1.266,95%CI:1.185～1.353),FCP(β=0.361,OR=1.435,95%CI:1.227～1.678)、FINS(β=0.059,OR=1.061,95%CI:1.040～1.082)were still independent risk factors for aggravating the development of liver fibrosis,and ISImatsuda(β=0.008,OR=0.992,95%CI:0.984～0.999)is protective factors for delaying liver fibrosis(P<0.05).In addition,Pearson correlation analysis showed that NFS level was positively correlated with HOMA-IR(r=0.482),FCP(r=0.405),FINS(r=0.543),(P<0.05,P<0.001).3.Research on the value of IR in the diagnosis and prediction of liver fibrosis in NAFLD:ROC curve plot showed that HOMA-IR,FCP and FINS could be used for the diagnosis of advanced liver fibrosis in T2DM complicated with NAFLD(the curve area under ROC was all greater than 0.70).When HOMA-IR=9.895,the sensitivity and specificity reached 75.80%and 71.60%.FCP=2.735ng/mL,the sensitivity was 69.40%,the specificity was 72.90%.FINS=20.67 mu/L,sensitivity was 67.70%,specificity was 82.60%.Conclusions 1.T2DM patients with high levels of HOMA-IR,AUCI/AUCG,FCP and FINS were more likely to have NAFLD.2.HOMA-IR,FCP,FINS were independently associated with liver fibrosis in T2 DM patients with NAFLD.IR is risk factor for promoting the development of liver fib rosis in NAFLD.3.HOMA-IR,FINS and FCP levels were positively correlated with NFS,which could be used for early screening and evaluation of liver fibrosis in NAFLD.