Low normal thyroid function enhances plasma cholesteryl ester transfer in Type 2 diabetes mellitus

• Published in: Atherosclerosis Vol. 228; no. 2; pp. 466 - 471
• Main Authors: Triolo, Michela, Kwakernaak, Arjan J, Perton, Frank G, de Vries, Rindert, Dallinga-Thie, Geesje M, Dullaart, Robin P.F
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.2013
• Subjects: Aged; atherosclerosis; Biomarkers - blood; blood glucose; Blood Glucose - analysis; body mass index; Cardiovascular; Case-Control Studies; Chi-Square Distribution; cholesterol; Cholesterol Ester Transfer Proteins - blood; Cholesteryl ester transfer; Cholesteryl ester transfer protein; cholesteryl esters; correlation; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Euthyroidism; Female; Glycated Hemoglobin A - analysis; high density lipoprotein; Humans; hyperglycemia; Linear Models; low density lipoprotein; Male; metabolism; Middle Aged; Multivariate Analysis; noninsulin-dependent diabetes mellitus; Predictive Value of Tests; Reference Values; regression analysis; thyroid function; Thyroid Function Tests; Thyroid Gland - metabolism; Thyroid Gland - physiopathology; Thyroid-stimulating hormone; thyrotropin; Thyrotropin - blood; thyroxine; Thyroxine - blood; triacylglycerols; Triglycerides; Triglycerides - blood; Type 2 diabetes mellitus; Up-Regulation; Thyroid-stimulating hormone; Triglycerides; Type 2 diabetes mellitus; Cholesteryl ester transfer; Euthyroidism; Cholesteryl ester transfer protein
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2013.03.009

Abstract Background Plasma cholesteryl ester transfer (CET), reflecting endogenous transfer of cholesteryl esters from HDL to very low and low density lipoproteins, is elevated in Type 2 diabetes mellitus (T2DM), and may predict (subclinical) cardiovascular disease. Low normal thyroid function may adversely affect lipoprotein metabolism and atherosclerosis development. We tested whether plasma CET is related to thyroid function in euthyroid T2DM and non-diabetic subjects. Subjects and methods Plasma CET was measured in 74 T2DM and 82 non-diabetic subjects with thyroid-stimulating hormone (TSH) and free thyroxine levels within the reference range. Results Plasma CET was 20% higher in T2DM ( P  = 0.003) coinciding higher cholesteryl ester transfer protein (CETP) mass ( P  = 0.009) and triglycerides ( P  = 0.02). In univariate analysis, plasma CET was correlated positively with TSH in T2DM only ( r  = 0.330, P  = 0.004). Multiple linear regression analysis revealed a positive interaction between the presence of T2DM and TSH on plasma CET after controlling for age, sex, body mass index, non-HDL cholesterol, triglycerides and CETP mass (β = 0.167, P  = 0.030). The relationship of plasma CET with TSH was also positively modified by plasma glucose and HbA1c (interaction terms: β  = 0.119, P  = 0.036, β  = 0.170, P  = 0.001, respectively). Additionally, plasma triglycerides interacted positively with TSH on plasma CET in T2DM ( β  = 0.198, P  = 0.011). Conclusions Low normal thyroid function, as inferred from higher TSH, confers increased plasma CET in the context of chronic hyperglycemia. Effects of thyroid function on plasma CET may be particularly relevant in hypertriglyceridemic T2DM. Low normal thyroid function could influence atherosclerosis susceptibility in T2DM by affecting the plasma cholesteryl ester transfer process.