Low normal free T4 confers decreased high‐density lipoprotein antioxidative functionality in the context of hyperglycaemia

Abstract

Low normal thyroid function may promote the development of atherosclerotic cardiovascular disease by thus far poorly defined mechanisms. We tested the impact of thyroid function on HDL antioxidative capacity, a metric of its antiatherogenic functionality, in euthyroid subjects with varying degrees of glucose tolerance. Seventy subjects with Type 2 diabetes mellitus (T2DM), 37 subjects with impaired fasting glucose (IFG) and 31 subjects with normal fasting glucose (NFG) (revised NCEP-ATPIII criteria) participated in a cross-sectional study. HDL antioxidative capacity (standardized for HDL cholesterol) was measured as the percentage inhibition of low-density lipoprotein oxidation in vitro. TSH, free T4 and HDL antioxidative capacity were not different among NFG, IFG and T2DM subjects (P > 0·25 for each). HDL antioxidative capacity was correlated positively with free T4 (r = 0·320, P = 0·007), and negatively with plasma glucose (r = -0·394, P < 0·001) in T2DM only. Taking account of age and sex, the relationship of HDL antioxidative functionality with free T4 was modified by glucose tolerance status (P = 0·040 and P = 0·008 for interactions of IFG and T2DM with free T4 respectively). Prevailing plasma glucose also interacted positively with free T4 on HDL antioxidative capacity (P = 0·054). In the context of chronic hyperglycaemia, low free T4 within the euthyroid range confers diminished HDL antioxidative capacity, a pathophysiologically relevant metric of HDL functionality.