HDLS CONTAINING APOLIPOPROTEINS A-I AND A-II (LPA-I-A-II) AS MARKERS OF CORONARY-ARTERY DISEASE IN MEN WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Background Abnormalities in HDL and an increased risk of coronary arte ry disease (CAD) coexist in non-insulin-dependent diabetes mellitus (N IDDM). HDLs can be separated by their apolipoprotein (apo) content int o particles containing apoA-I but not apoA-II (LpA-I) and those contai ning both apoA-I and apoA-II (LpA-I:A-II). The LpA-I particles have be en suggested to be more effective in conferring protection against CAD than the LpA-I:A-II particles. However, data are sparse, and no studi es have defined the role of these two classes of particles in NIDDM. M ethods and Results LpA-I and LpA-I:A-II particles were quantified by a differential electroimmunoassay in four groups of men with similar ag e and body mass index (BMI) distributions. Group 1 consisted of 50 pat ients with NIDDM and angiographically verified CAD; group 2, 50 men wi th CAD but no diabetes; group 3, 50 men with NIDDM but no CAD; and gro up 4, 31 healthy men. Serum apoA-I and apoA-II concentrations were mea sured by immunoturbidimetry, and HDL(2) and HDL(3) were separated by u ltracentrifugation. Concentrations of LpA-I:A-II particles in group 1 were 13.8%, 18.3%, and 26.9% lower than in groups 2 through 3, respect ively. In a two-by-two factorial ANOVA, adjusted for age and BMI, the differences were significant for both CAD (P<.001) and NIDDM (P<.001), with no interaction between the factors. These results were confirmed by comparable differences in the serum concentrations of apoA-I and a poA-II. LpA-I particles were related to the presence or absence of CAD (P=.013), but the difference was lost in a multivariate analysis. A l ow HDL(3) cholesterol concentration characterized both CAD (P=.002) an d NIDDM (P=.024). HDL(2) cholesterol differed significantly with regar d to the presence of NIDDM (P=.033) but only borderline with respect t o CBD (P=.073). Conclusions ApoA-II-containing lipoproteins and HDL(3) cholesterol are powerful markers of CAD in men with NIDDM.