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

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. 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. 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). 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.

Triolo M ，Kwakernaak AJ ，Perton FG ，de Vries R ，Dallinga-Thie GM ，Dullaart RP ... -  《-》

Increased large VLDL particles confer elevated cholesteryl ester transfer in diabetes.

Plasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to which the relationship of plasma CET with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions is modified in T2DM. Plasma CET, cholesteryl ester transfer protein (CETP) mass, as well as VLDL and LDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 62 patients with T2DM and 53 nondiabetic subjects. Plasma CET and CETP mass were increased in T2DM, coinciding higher triglycerides and large VLDL particles (all P < 0·02). Plasma CET was positively related to the VLDL and the LDL particle concentration in age-, sex- and diabetes status-adjusted analysis (both P < 0·001). Multivariable linear regression analysis demonstrated an independent positive interaction between the presence of T2DM and the VLDL concentration on plasma CET (β = 0·238, P = 0·033). The relationship of plasma CET with the VLDL concentration was also positively modified by plasma glucose (β = 0·211, P = 0·004) and glycated haemoglobin (β = 0·190, P = 0·012). Of the individual VLDL subfractions, a positive interaction of diabetes status with large VLDL on plasma CET was observed (β = 0·280, P = 0·003). Neither the relationship of the LDL particle concentration nor of CETP mass with plasma CET was modified by the presence of T2DM (P > 0·15). Abnormalities in the concentration and composition of large VLDL particles are likely to contribute to elevated plasma CET in T2DM.

Dullaart RP ，de Vries R ，Kwakernaak AJ ，Perton F ，Dallinga-Thie GM ... -  《-》

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.

van Tienhoven-Wind LJ ，Dallinga-Thie GM ，Dullaart RP 《-》

Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects: role of CETP and triglycerides.

de Vries R ，Perton FG ，Dallinga-Thie GM ，van Roon AM ，Wolffenbuttel BH ，van Tol A ，Dullaart RP ... -  《-》

Low normal thyroid function as a determinant of increased large very low density lipoprotein particles.

Low-normal thyroid function may relate to increases in plasma cholesterol and triglycerides, but effects on lipoprotein subfractions are largely unknown. Associations of alterations in lipoprotein metabolism and functionality with low-normal thyroid function could be more pronounced in Type 2 diabetes mellitus (T2DM). We determined relationships of plasma lipids and lipoprotein subfractions with thyroid-stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects, and assessed whether such relationships are modified in the context of T2DM. TSH, free T4, (apo)lipoproteins and lipoprotein subfractions (nuclear magnetic resonance spectroscopy) were measured after an overnight fast in 61 T2DM subjects and 52 non-diabetic subjects. TSH and free T4 were similar in T2DM and non-diabetic subjects. Plasma triglycerides, large very low density (VLDL) particles, VLDL size and small low density lipoprotein (LDL) particles were increased, whereas high density lipoprotein (HDL) cholesterol was decreased in T2DM subjects (p ≤ 0.05 for each). Age-, sex-, and diabetes status-adjusted multivariable linear regression analysis demonstrated that plasma triglycerides were associated positively with TSH (β=0.196, p=0.039). Large VLDL particles (β=-0.215, p=0.020) and VLDL size were inversely associated with free T4 (β=-0.285, p<0.001). These relationships were not significantly modified by diabetes status (interaction terms: p>0.10 for each). In all subjects combined, LDL and HDL subfraction characteristics were not significantly related to thyroid function status. Low-normal thyroid function may confer increased plasma triglycerides, large VLDL particles and increased VLDL particle size. These relationships are not to a major extent modified in the context of T2DM.

van Tienhoven-Wind L ，Dullaart RP 《-》