Association Between Sensitivity To Thyroid Hormones And Metabolic Phenotype Of Obesity In Euthyroid Subjects

ObjectiveThyroid hormone plays an important role in regulating energy metabolism.To date,the link between thyroid hormones sensitivity and different metabolic phenotypes of obesity remains unknown.Thus,this study intends to investigate the association between the indicators of thyroid function,sensitivity to thyroid hormones and different metabolic phenotypes of obesity in euthyroid subjects.MethodsIn this cross-sectional study,781 euthyroid subjects who had complete baseline data and were hospitalized in our hospital between December 2019 and November 2022 were included.Demographic information,biochemical parameters,and indicators of thyroid function were collected.FT3/FT4 ratio,PTFQI,TT4RI as well as TSHI,which reflected the peripheral and central sensitivity to thyroid hormones respectively were calculated.According to the diagnostic criteria of overweight/obesity and metabolic syndrome,the patients were divided into metabolically healthy with overweight/obesity(MHO)and metabolically unhealthy with overweight/obesity(MUO).Then,the clinical characteristics of the two groups were further compared.Pearson and/or Spearman correlation analysis between the indicators of thyroid function,sensitivity to thyroid hormones and clinical parameters was performed.To further exclude the interference of cofounding factors,logistic regression analysis was used to evaluate the correlation between thyroid parameters and the risk of MUO.Receiver operating characteristic(ROC)was also analyzed to evaluate the effectiveness of FT3/FT4 ratio in predicting MUO.ResultsAmong 781 subjects enrolled in this study,665(85.1%)met the diagnostic criteria for metabolically unhealthy with overweight/obesity.MHO and MUO groups had differences in baseline characteristics such as age,gender,BMI,SBP,DBP,FPG,HbAlc,Cr,TG,HDL-C,and the proportion of diabetes,hypertension,dyslipidemia as well as fatty liver(P<0.05).Compared with MHO group,MUO group had increased level of FT4,PTFQI and decreased level of FT3/FT4 ratio(P<0.05).The level of FT3/FT4 ratio of female patients was negatively associated with the level of age,SBP,FPG,HbA1c,Urea,Cr and TC,while positively associated with the level of ALT.Besides,the level of FT3/FT4 ratio of male patients was negatively associated with FPG,HbAlc,Urea,while positively associated with BMI,ALT and AST(P<0.05).In addition,the study population were divided into three groups according to the FT3/FT4 ratio tertiles and the proportion of MUO patients was significantly different in the FT3/FT4 tertiles groups.The proportion of MUO was 91.2%in T1 group,83.9%in T2 group and 80.3%in T3 group,respectively(P=0.002).However,multivariate logistic regression analysis adjusting for confounding factors such as age,gender and BMI,showed that the risk of MUO was negatively associated with the level of FT3/FT4 ratio(OR=0.452,95%CI:0.244-0.838),while was not significantly associated with the level of PTFQI,TSHI and TT4RI.Compared with subjects in the lowest tertiles of FT3/FT4 ratio,those in the highest tertiles had lower risk of MUO(OR=0.322,95%CI:0.159-0.649).Subgroup analysis showed that the association remained significant in female and<65 years old euthyroid subjects.The FT3/FT4 ratio was selected for predicting MUO in euthyroid subjects and the area under the ROC curve was 0.617.Additionally,the area under the ROC curve for female subjects was 0.658 and the specificity was high.ConclusionIncreased levels of FT3/FT4 ratio(indicators of peripheral sensitivity to thyroid hormones)were associated with lower risk of MUO in euthyroid subjects,and the results differed between genders and ages.Peripheral thyroid hormone sensitivity index can be used as an essential reference index to evaluate or predict the occurrence of metabolically unhealthy with overweight/obesity.