Free triiodothyronine/free thyroxine (FT3/FT4) ratio is strongly associated with insulin resistance in euthyroid and hypothyroid adults: a cross-sectional study

Introduction: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if being early detected and mitigated, for lowering the burden of the diseases. Available data are conflicting to what extent adult thyroid dysfunction is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR. Material and Methods: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tolerance test (OGTT) and insulin, 1425 middle-aged individuals were divided into three groups according to the thyroid parameters: overt hypothyroidism (OH), subclinical hypothyroidism (SH) and euthyroidism (EU). Results: The homeostasis model assessment of IR (HOMA-IR), fasting insulin and 2-hour glucose levels of OGTT showed a steady, yet insignificant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically significant correlations were observed with FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid hormones, linear logistic regression proved the FT3/FT4 ratio as the only significant predictor of HOMA-IR (linear coefficient = 5.26, p = 0.027) and insulin levels (linear coefficient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR in either correlation or regression analysis. Conclusions: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benefit from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a risk of the cardiometabolic diseases.