Fd. Brites et al., Abnormal capacity to induce cholesterol efflux and a new LpA-I pre-beta particle in type 2 diabetic patients, CLIN CHIM A, 279(1-2), 1999, pp. 1-14
In this study, we first characterized the lipoprotein components of serum s
amples obtained from a group of well-controlled diabetic patients and from
healthy subjects in fasting and postprandial states. We then explored some
aspects of reverse cholesterol transport in the same population. Patients s
howed high levels of fasting triglycerides, postprandial triglyceride respo
nses and LpC-III levels (3.18+/-0.86 vs 2.17+/-0.54 mg/dl, P < 0.001). Ther
e were also positive correlations between LpC-III and fasting triglycerides
(r = 0.82, P < 0.001), total triglyceride area (r = 0.75, P < 0.001) and i
ncremental triglyceride area (r = 0.54, P <0.001). HDL-C and apo A-I were s
ignificantly decreased in diabetic patients due to a selective reduction in
LpA-I subfraction, whose antiatherogenic role is generally accepted (37.4/-8.0 vs 49.2+/-12.5 mg/dl, P < 0.001). In addition, HDL from patients prov
ed to be triglyceride enriched and cholesteryl ester depleted, alterations
which were further amplified in the postprandial state. The molar ratio HDL
-C/apo A-I + apo A-II, already defined as a predictor of apo A-I fractional
catabolic rate, was significantly diminished in the patient group (15.1+/-
2.2 vs 20.8+/-3.3, P<0.001), thus suggesting an accelerated catabolism of a
po A-I. For the first time, we describe here the presence of a small apo A-
I-containing particle, isolated by two-dimensional electrophoresis and char
acterized by immunoblotting, only in samples From diabetic patients. This p
article that we named pre-P,, has an apparent molecular weight of 30 kDa. A
s regards the capacity of serum samples to promote cholesterol efflux from
[H-3]cholesterol-labeled Fu5AH rat hepatoma cells, patient samples were Fou
nd to induce significantly lower cholesterol efflux than controls only in t
he postprandial state (21.2+/-3.3 vs 23.8+/-1.8%, P = 0.012). The presence
of pre-P, in samples from diabetic patients might therefore be associated t
o an altered capacity of these serum samples to promote cellular cholestero
l efflux. Overall, these abnormalities may contribute to a delay in the rev
erse cholesterol transport pathway in type 2 diabetic patients. (C) 1999 El
sevier Science B.V. All rights reserved.