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

This study examines the activity of two key enzymes of reverse cholest erol transport, cholesterol ester transfer protein (CETP) and lecithin :cholesterol acyl transferase (LCAT) in 21 patients with non-insulin d ependent 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. Th ere was no significant difference in CETP mass between the diabetic an d non-diabetic subjects and there was no correlation between CETP mass and LCAT activity. Using the endogenous lipoprotein assay, CETP was e levated 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 in creased in the diabetic patients (53.63 +/- 4.70 vs. 41.22 +/- 3.40 nm ol/ml/h P < 0.05). Serum free cholesterol from diabetic and control su bjects correlated with CETP activity measured using endogenous lipopro tein assay (r = 0.77, P < 0.001 and r = 0.82, P < 0.001), and also wit h 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 lipo protein assay and serum high density lipoprotein (HDL) cholesterol. in the diabetic patients (r = -0.38, P < 0.01), but not in control subje cts. In a subgroup of 10 control subjects, there was a positive correl ation between LCAT activity and apolipoprotein (ape) A-I (r = 0.49, P < 0.05) and apo A-II (r = 0.51, P < 0.05) and also between CETP activi ty (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 activit y and apo A-I or apo A-II in the diabetic subjects. Thus, serum CETP m ass was normal in Type 2 diabetes but CETP activity (endogenous assay) was increased and was related to free cholesterol levels and LCAT act ivity in both diabetic and non-diabetic subjects.