The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects

High levels of TSH are associated with an increased cardiovascular risk. Ma ny cardiovascular risk factors cluster within the insulin resistance syndro me. It is not known whether levels of TSH cluster as well. We conducted thi s research to test the hypothesis that TSH, insulin sensitivity, and levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotei n cholesterol (HDL-C) are interdependent in euthyroid subjects. Levels of T SH, free thyroid hormone, and serum Lipids were measured in fasting serum s amples taken before performance of a hyperinsulinemic euglycemic clamp to a ssess insulin sensitivity in 46 healthy euthyroid subjects with a mean TSH of 1.8 +- 0.7 mU/L. Significant age- and sex-adjusted partial correlations of TSH with LDL-C (r = 0.48; P < 0.01) and HDL-C (r = -0.36; P < 0.05) were observed. TSH was not significantly correlated with insulin sensitivity or fasting triglyceride concentrations. In line with these results, we found the associations of TSH with LDL-C and HDL-C to be independent of insulin s ensitivity. However, we observed significant effect-modification of the ass ociation of TSH with LDL-C by insulin sensitivity (P = 0.02). This effect-m odification implies a range of associations of TSH with LDL-C that varies f rom absent in insulin-sensitive subjects to strongly positive in insulin-re sistant subjects. We conclude that the increased cardiovascular risk associ ated with subclinical hypothyroidism seems to extend itself into the normal range of thyroid function. Importantly, the effect-modification of the ass ociation of TSH with LDL-C by insulin sensitivity suggests that insulin-res istant subjects are most susceptible to this increased risk.