| Objective:Metabolic-associated fatty liver disease(MAFLD)is a metabolic liver disease closely related to type 2 diabetes mellitus(T2DM).MAFLD and T2 DM often coexist and cooperate with each other.The prevalence of MAFLD and T2 DM is increasing rapidly worldwide,and the combination of the two increases the risk of adverse liver and extrahepatic outcomes.Many studies have shown that insulin-like growth factor I(IGF-I)and insulin-like growth factor binging protein 3(IGFBP-3)can participate in glucose homeostasis and hepatocyte injury by affecting glucose and lipid metabolism and insulin sensitivity.In this study,we explored the correlation between liver fibrosis and IGF-I and IGFBP-3 in T2 DM patients with MAFLD,provided predictors for the degree of liver fibrosis in T2 DM patients with MAFLD,and analyzed the mechanism of IGF-I and IGFBP-3 affecting the occurrence and development of liver fibrosis in T2 DM patients with MAFLD.Methods:In this study,a total of 380 individuals suffering from T2 DM and MAFLD,who had been hospitalized in our department from December 2020 to August 2021 were included.According to the Hepamet fibrosis score,they were divided into three groups :1)there were 227 cases in the low-risk group of T2 DM combined with MAFLD liver fibrosis(Hepamet liver fibrosis score<0.12);2)there were 112 cases in the moderate risk group of T2 DM combined with MAFLD liver fibrosis(0.12≤ Hepamet liver fibrosis score≤0.47);3)there were 41 cases in the high-risk group of T2 DM combined with MAFLD liver fibrosis(Hepamet liver fibrosis score>0.47).The general data of all patients were collected : gender,age,duration of diabetes,body mass index(BMI),and blood biochemical indexes : fasting plasma glucose(FPG),glycosylated hemoglobin(Hb Alc),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),fasting serum insulin(FINS),alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB),platelets(PLT),IGF-I,IGFBP-3 were measured,and homeostasis model assessment of insulin resistance was calculated,also known as homeostasis model assessment of insulin resistance(HOMA-IR)and Hepamet liver fibrosis score.SPSS26.0 was used to analyze the data by single factor variance test,non-parametric test,logistics regression analysis,Pearson correlation analysis and other statistical methods.Results:1.In this study,the general data and clinical indicators of patients were compared between groups,and it was found that there was no significant difference in Hb Alc,FINS,BMI,ALT,TC,HDL-C and LDL-C between groups with different degrees of liver fibrosis(P>0.05);there were significant differences in age,sex,course of disease,AST,TG,PLT,ALB,HOMA-IR,FPG,IGF-I and IGFBP-3 between different groups with different degrees of liver fibrosis(P<0.05).There were significant differences in age,ALB,TG and IGF-I between the low-risk group and the other two groups.The high-risk group of AST was significantly different from the other two groups.There were significant differences between the low-risk group and the middle-risk group in course of disease,IGFBP-3 and FPG.There was significant difference between HOMA-IR low-risk group and high-risk group.PLT was significantly different among the three groups(P < 0.05).2.The results of multivariate logistic regression analysis showed that age,gender,IGFBP-3,AST,ALB,PLT,HOMA-IR and TG were independent factors affecting the severity of liver fibrosis(P<0.05).There was a significant positive correlation between age,AST,gender,HOMA-IR and the severity of liver fibrosis.The levels of IGFBP-3,ALB,PLT and TG had a significant negative effect on the degree of liver fibrosis.This indicates that AST,age,HOMA-IR and women are risk factors for the degree of liver fibrosis in T2 DM with MAFLD,and IGFBP-3,ALB,PLT and TG are protective factors for the degree of liver fibrosis in T2 DM with MAFLD.3.The middle-risk group and the high-risk group were renamed as the liver fibrosis group(n=153),and the low-risk group was named as the non-liver fibrosis group(n=227).The receiver operating characteristic curve(ROC)curve showed that the area under the curve(AUC)of IGF-I,IGFBP-3,and the combination of the two was0.626,0.645,and 0.643,respectively(P<0.001).The optimal cut-off value of IGF-I in the diagnosis of liver fibrosis was 127.5,and the Youden index was 0.45.The sensitivity and specificity of predicting the degree of liver fibrosis in T2 DM with MAFLD were0.768 and 0.218,respectively.The optimal cut-off value of IGFBP-3 in the diagnosis of liver fibrosis was 4.125,and the Youden index was 0.40.The sensitivity and specificity of predicting the degree of liver fibrosis in T2 DM with MAFLD were 0.848 and 0.248,respectively.The Youden index of combined diagnosis of liver fibrosis was0.41,the sensitivity of predicting the degree of liver fibrosis in T2 DM with MAFLD was 0.727,and the specificity was 0.247.4.No significant correlation between serum IGF-I and HOMA-IR,TG,TC,LDLC,HDL-C,FPG,and Hb Alc was revealed by Pearson correlation analysis(P>0.05).There was a significant correlation between serum IGFBP-3 and HOMA-IR(r=0.125,P<0.05),TG(r=0.270,P<0.01),TC(r=0.224,P<0.01),LDL-C(r=0.109,P<0.05),FPG(r=0.190,P<0.01),Hb Alc(r=0.128,P<0.05),and there was a positive correlation.There was no significant correlation between HDL-C(P>0.05).Conclusion:1.Age,female,IGFBP-3,AST,ALB,PLT,HOMA-IR and TG are independent factors affecting the severity of liver fibrosis in T2 DM with MAFLD.2.Serum IGF-I,IGFBP-3 and their combination have predictive value for the degree of liver fibrosis in T2 DM with MAFLD,and the more severe the degree of liver fibrosis,the lower the levels of serum IGF-I and IGFBP-3.3.Serum IGFBP-3 can affect the progression of liver fibrosis in T2 DM patients with MAFLD by increasing insulin resistance and interfering with glucose and lipid metabolism.Although serum IGF-I can be used as a predictor of liver fibrosis in T2 DM with MAFLD,the mechanism of serum IGF-I affecting its pathogenesis has not been found yet,which needs further study. |
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