Increased esterification of cholesterol and transfer of cholesteryl ester to apo B-containing lipoproteins in Type 2 diabetes: relationship to serum lipoproteins A-I and A-II

Abstract

This study examines the activity of two key enzymes of reverse cholesterol transport, cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 patients with non-insulin dependent diabetes mellitus (NIDDM) and 21 control subjects. Serum CETP was assessed by measuring plasma-mediated cholesteryl ester transfer between pooled exogenous lipoprotein with endogenous LCAT inhibited — an estimate of CETP mass. CETP activity was determined as cholesteryl ester transfer in the presence of the patients' lipoproteins and LCAT (endogenous assay). LCAT activity was determined in the same assay. There was no significant difference in CETP mass between the diabetic and non-diabetic subjects and there was no correlation between CETP mass and LCAT activity. Using the endogenous lipoprotein assay, CETP was elevated in serum from diabetic patients compared to control subjects (10.05 ± 1.89 vs. 5.50 ± 0.53 nmol/ml/h P < 0.05). LCAT was also increased in the diabetic patients (53.63 ± 4.70 vs. 41.22 ± 3.40 nmol/ml/h P < 0.05). Serum free cholesterol from diabetic and control subjects correlated with CETP activity measured using endogenous lipoprotein assay ( r = 0.77, P < 0.001 and r = 0.82, P < 0.001), and also with LCAT activity ( r = 0.76, P < 0.01 and r = 0.79, P < 0.01). There was a negative correlation between CETP activity with the endogenous lipoprotein assay and serum high density lipoprotein (HDL) cholesterol in the diabetic patients ( r = −0.38, P < 0.01), but not in control subjects. In a subgroup of 10 control subjects, there was a positive correlation between LCAT activity and apolipoprotein (apo) A-I ( r = 0.49, P < 0.05) and apo A-II ( r = 0.51, P < 0.05) and also between CETP activity (endogenous assay) and apo A-I ( r = 0.87, P = 0.001) and apo A-II ( r = 0.63, P < 0.05). No relationship was observed between CETP activity and apo A-I or apo A-II in the diabetic subjects. Thus, serum CETP mass was normal in Type 2 diabetes but CETP activity (endogenous assay) was increased and was related to free cholesterol levels and LCAT activity in both diabetic and non-diabetic subjects.