Study On The Association Of Serum Thyroid Stimulating Hormone With Non-alcoholic Fatty Liver Disease In Euthyroid Subjects

Objective: Non-alcoholic fatty liver disease(NAFLD)is emerging as a global epidemic,and the prevalence rate of NAFLD is increasing year by year.NAFLD is not only likely to develop into advanced liver disease,cirrhosis and hepatocellular carcinoma,but also affects extrahepatic organs and extrahepatic regulatory pathways,and is associated with the presence and progression of cardiovascular diseases,diabetes mellitus,chronic kidney disease,colorectal tumors and polycystic ovary syndrome.Currently,there is a lack of effective treatment for NAFLD,and the study of its risk factors can lead to early and effective intervention and delay the progression of the disease.Multiple studies have shown that serum thyroid stimulating hormone(TSH)levels are significantly associated with NAFLD in hypothyroidism and subclinical hypothyroidism.However,the conclusions on the relationship between TSH and NAFLD are inconsistent in people with normal thyroid function.The purpose of this study is to investigate the relationship between TSH with NAFLD in euthyroid subjects.Methods: A total of 444 eligible subjects were included,including 80 normal population,90 study subjects with simple NAFLD,49 study subjects with simple type 2 diabetes mellitus(T2DM),and 225 study subjects with NAFLD and T2 DM.To obtain clinical indicators such as body mass index(BMI),blood pressure(BP),serum 25 hydroxyvitamin D(25(OH)D),albumin,total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),alkaline phosphatase(ALP),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamine transferase(GGT),free fatty acid(FFA),fasting plasma glucose(FPG),2-hour postprandial blood glucose(2h PG),fasting insulin(FIN),glycosylated hemoglobin(Hb A1c),serum creatinine(CR),urinary microalbumin(MALB),blood uric acid(UA),urinary albumin/creatinine ratio(UACR),thyroid stimulating hormone(TSH)of eligible subjects from the hospital information management system and the data were input into Excel.Homeostasis model insulin resistance index(HOMR-IR)=FPG(mmol/L)×FIN(MIU /L)/22.5.NAFLD was diagnosed by color ultrasound.SPSS 22.0 statistical software was used for statistical analysis.The measurement data did not meet normal distribution.The median and interquartile interval(IQR)were used to express the data.The non-parametric test was used to compare the differences between the two groups.Chi square test was used to compare the differences of data between multiple groups.Spearman correlation was used to analyze the correlation between TSH and other clinical indicators.Binary logistic regression was used to analyze the influencing factors of NAFLD.P<0.05 indicates statistical significance.Results: 1.A total of 444 subjects were included,ranging in age from 18 to 82 years old,including 190 males,accounting for 42.80%.Among them,315 patients met the diagnostic criteria for NAFLD,and the prevalence of NAFLD was 70.95%,which were defined as the NAFLD group,while 129 patients without NAFLD were defined as the non-NAFLD group.Comparison between groups showed that the levels of age,BMI,SBP,DBP,albumin,ALT,AST,ALP,GGT,Hb A1 c,FPG,FIN,HOMR-IR,UA,TG,TC and FFA in NAFLD group were higher than those in non-NAFLD group(P<0.05).The levels of Cr,HDL-C and TSH in NAFLD group were lower than those in non-NAFLD group(P<0.05).There were no significant differences in gender,2h PG,m ALB,UACR,LDL-C,25(OH)D levels between the two groups.2.All subjects were divided into four subgroups according to TSH level.In the whole population,the prevalence of NAFLD in TSH groups Q1-Q4 was 82.30%,73.39%,70.80% and 56.88%,showing an increasing trend(χ~2=17.848,P<0.001).Among females,the prevalence of NAFLD was 84.40%,76.30%,75.40% and 57.60% respectively(χ~2=12.737,P=0.005).In males,there was no significant difference in the prevalence of NAFLD among all groups(χ~2=6.298,P=0.098).3.Spearman correlation analysis of TSH and metabolic parameters showed that serum TSH level of normal thyroid function was positively correlated with albumin,HDL-C and 25(OH)D levels,and negatively correlated with DBP,Hb A1 c,HOMR-IR,TG,FPG and 2h PG.After adjusting for age and sex,TSH was positively correlated with albumin(r=0.190,P=0.004),HDL-C(r=0.202,P=0.002),25(OH)D(r=0.188,P=0.004),and was negatively correlated with DBP(r=-0.129,P=0.049),Hb A1c(r=-0.201,P=0.002),FPG(r=-0.156,P=0.017)and 2h PG(r=-0.266,P=0.000).4.Multivariate regression analysis showed that the influencing factors of NAFLD were BMI(OR: 1.240,95%CI: 1.089~1.414,P=0.001),ALT(OR: 1.084,95%CI:1.042~1.128,P<0.001),ALP(OR:1.023,95%CI:1.002~ 1.045,P=0.031),TG(OR: 5.469,95%CI: 2.822~10.596,P<0.001).Conclusion: 1.The level of TSH in NAFLD group was lower than that in non-NAFLD group,and the difference was statistically significant;2.BMI,ALT,ALP and TG are independent risk factors for NAFLD;3.TSH is not an independent influencing factor of NAFLD in euthyroid subjects.