Association between Lower Normal Free Thyroxine Concentrations and Obesity Phenotype in Healthy Euthyroid Subjects

We investigated whether thyroid function could identify obesity phenotype in euthyroid subjects. A cross-sectional analysis was performed among nondiabetic, euthyroid subjects. We stratified subjects into four groups by BMI and insulin resistance (IR). Of 6241 subjects, 33.8% were overweight or obese (OW/OB) and 66.2% were normal weight (NW). Free thyroxine (FT4) levels were negatively associated with body mass index, waist circumference, triglyceride, c-reactive protein, and HOMA-IR and positively with high-density lipoprotein cholesterol in both genders. In multivariate regression analysis, FT4 level, a continuous measurement, was negatively correlated with HOMA-IR (beta --0.155,P < 0.001 in men;beta--0.175, P < 0.001 in women). After adjustment for age, sex, metabolic, and life style factors, subjects in the lowest FT4 quartile had an odds ratio (OR) for IR of 1.99 (95% confidence interval 1.61-2.46), as compared to those in the highest quartile. The association between low FT4 and IR remained significant in both NW and OW/OB subgroups. In conclusion, low normal FT4 levels were independently related to IR in NW and OW/OB euthyroid subjects. Further studies are needed to investigate the mechanisms by which low FT4 levels are linked to high IR in euthyroid ranges.