Tumor Necrosis Factor-α is Inversely Related to Free Thyroxine in Euthyroid Subjects Without Diabetes.

Lower thyroid functional status within the euthyroid range may confer increased atherosclerosis susceptibility, as evidenced by increased intima media thickness and coronary artery calcification. Associations of lower thyroid functional status with pro-atherogenic (inflammatory) biomarkers may also extend into the euthyroid range. Here we established relationships of plasma tumor necrosis factor-α (TNF-α) with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). Fasting TSH, free T4, and TNF-α were measured in 81 nondiabetic subjects and in 73 T2DM subjects with Type 2 diabetes mellitus (T2DM; insulin using subjects were excluded) with TSH and free T4 levels each within the institutional reference ranges. TSH was similar and free T4 was slightly higher in T2DM (p<0.016). Plasma TNF-α was increased in T2DM (p=0.007). In nondiabetic subjects, TNF-α was correlated inversely with free T4 (r=-0.254, p=0.022), whereas such a relationship was absent in T2DM subjects (r=0.058, p=0.63). Multivariable linear regression analysis showed that in nondiabetic subjects TNF-α remained inversely associated with free T4 after adjustment for age and sex (ß=-0.243, p=0.032) and additionally for thyroid autoantibodies (ß=-0.251, p=0.027), contrasting the lack of relationship in T2DM subjects (interaction: p=0.053). In T2DM subjects, TNF-α was also unrelated to free T4 taking account of possible confounders, as well as after exclusion of subjects using metformin or antihypertensive medication. In conclusion, higher levels of TNF-α relate to lower free T4. Low-normal thyroid function could influence pro-inflammatory pathways. This relationship appears to be disturbed in T2DM.

Higher Plasma ApoE Levels are Associated with Low-Normal Thyroid Function: Studies in Diabetic and Nondiabetic Subjects.

Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation.