statement of the problem: Low levels of high-density lipoprotein cholestero
l (HDL-C) have a strong association with coronary artery disease (CAD) in p
atients with non-insulin-dependent diabetes mellitus (NIDDM). In this study
, we tried to evaluate whether one or both of the major HDL subclasses (HDL
2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. Met
hods: The separation of HDL subclasses was carried out by ultracentrifugati
on in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant an
d its cholesterol content was measured enzymatically. Plasma HDL3 cholester
ol was calculated as the difference between results for total HDL cholester
ol and HDL2 cholesterol. Results: NIDDM patients with CAD had significantly
higher triglyceride levels compared to either control (217.09 +/- 55.04 ve
rsus 89.62 +/- 31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09 /- 55.04 versus 156.28 +/- 46.39 mg/dl, P<.05). However, in the diabetic pa
tients with CAD, there was a statistically significant decrease in HDL chol
esterol (39.63<plus/minus>8.59 versus 55.86 +/- 13.49 mg/dl, P<.01), HDL2 c
holesterol (8.74<plus/minus>3.28 versus 16.95 +/-5.73 mg/dl, P<.001),and HD
L3 cholesterol (31.23<plus/minus>7.41 versus 38.91 +/-8.93 mg/dl, P<.05) in
comparison to nondiabetic controls. Moreover, in the comparison between no
n-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL
cholesterol (39.63<plus/minus>8.59 versus 46.13 +/-6.33 mg/dl, P<.05) and H
DL2 cholesterol (8.74<plus/minus>3.28 versus 11.84 +/-4.01 mg/dl, P<.02) we
re significantly reduced, while HDL3 cholesterol levels were (31.23<plus/mi
nus>7.41 versus 34.29 +/-7.94 mg/dl, P=.92) unaltered. Additionally, the pe
rcentage reduction of cholesterol in HDL2 fraction was proportionately grea
ter than the decrease in HDL3 subclass in both comparisons. Moreover, in NI
DDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol
by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to
controls and CAD subjects without NIDDM. Conclusions: In conclusion, HDL2 i
s the more variable subclass and reflects changes in HDL. This suggests tha
t the protective role of total I IDL against CAD is mainly mediated through
HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary hea
rt disease than total I-IDL, in non-insulin-dependent diabetes mellitus. (C
) 2001 Elsevier Science Inc. All rights reserved.