Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes.
BACKGROUND
Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism.


METHODS
The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h.


RESULTS
No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = -0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET.


CONCLUSIONS
Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.
Dullaart
R P
RP
University Hospital, Groningen, The Netherlands. R.P.F.Dullart@int.AZG.NL
Riemens
S C
SC
Scheek
L M
LM
Van Tol
A
A
D001055:Apolipoproteins B / Q000097:blood; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D006023:Glycoproteins; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D007328:Insulin; D008075:Lipoproteins, HDL; D014280:Triglycerides