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 ... -  《-》

Plasma cholesteryl ester transfer, but not cholesterol esterification, is related to lipoprotein-associated phospholipase A2: possible contribution to an atherogenic lipoprotein profile.

Dullaart RP ，Constantinides A ，Perton FG ，van Leeuwen JJ ，van Pelt JL ，de Vries R ，van Tol A ... -  《-》

Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus (NIDDM).

Elchebly M ，Porokhov B ，Pulcini T ，Berthezène F ，Ponsin G ... -  《-》

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus.

Bilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM). Plasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects. Triglycerides, large VLDL, small LDL and small HDL particles were increased (all p<0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p<0.05), coinciding lower bilirubin levels in T2DM (p<0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p<0.05 to p<0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p<0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p<0.05). Increased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.

Dullaart RP ，de Vries R ，Lefrandt JD 《-》

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 ... -  《-》