Low-Normal Free Thyroxine Confers Decreased Serum Bilirubin in Type 2 Diabetes Mellitus

Background: Bilirubin may confer cardiovascular protection because of its strong antioxidative properties. Both thyroid dysfunction and the diabetic state affect bilirubin metabolism. Here we tested whether low-normal thyroid function affects serum bilirubin among euthyroid subjects with and without type 2 diabetes mellitus (T2DM). Methods: Serum total bilirubin, thyrotropin and free thyroxine (free T4), transaminases, insulin sensitivity (homeostasis model assessment), and lipids were measured in 74 T2DM and 82 nondiabetic subjects with thyrotropin and free T4 levels within the euthyroid range. Results: Bilirubin was positively related to free T4 in T2DM subjects (r=0.370, p<0.001), but not in nondiabetic subjects (r=0.047, p=0.68). In age- and sex-adjusted multiple linear regression analysis, free T4 was found to interact positively with the presence of T2DM on serum bilirubin (interaction term: =0.251, p=0.024). This interaction remained present after additional adjustment for alcohol intake, aspartate aminotransferase and insulin sensitivity (interaction term: =0.222, p=0.043), or alternatively for cholesterol and triglycerides (interaction term: =0.203, p=0.057). Conclusions: Lower free T4 levels within the euthyroid range confer decreased bilirubin in T2DM. Low-normal thyroid function could enhance atherosclerosis susceptibility in T2DM by decreasing serum bilirubin.