DIABETIC POSTPRANDIAL TRIGLYCERIDE-RICH LIPOPROTEINS INCREASE ESTERIFIED CHOLESTEROL ACCUMULATION IN THP-1 MACROPHAGES

The risk of cardiovascular disease is increased in subjects with insul in-dependent diabetes mellitus (IDDM), although the mechanism remains unclear. To assess whether diabetic postprandial triglyceride (TG)-ric h lipoprotein (TGRLP) subfractions (S-f > 400, 100-400, and 20-100) is olated from non-obese, normolipidemic IDDM subjects (n = 14) are poten tially more atherogenic than lipoproteins from normal controls (n = 13 ), we measured cholesteryl ester (CE) synthesis and esterified cholest erol (EC) mass accumulation in THP-1 macrophages incubated with postpr andial TGRLP. Diabetic S-f > 400 and S-f 100-400 but not S-f 20-100 si gnificantly increased the mean (+/-SE) rate (pmol/mg cell protein/24 h ) of CE synthesis in THP-1 macrophages compared with normal controls ( S-f > 400, 673 +/- 26 v 301 +/- 64, P < .025; S-f 100-400, 560 +/- 27 v 298 +/- 39, P < .0005; S-f 20-100, 743 +/- 51 v 831 +/- 45). As well , all three diabetic TGRLP increased the mass of EC (mu g EC/mg cell p rotein/48 h) as compared with normal controls (S-f > 400, 4.9 +/- 0.61 v 2.9 +/- 0.50, P < .025; S-f 100-400, 5.7 +/- 0.91 v 3.4 +/- 0.34, P < .05; S-f 20-100, 5.4 +/- 0.7 v 3.2 +/- 0.52, P < .05). This effect is sustained for at least 7 hours postprandially and is greater than t hat of fasting S-f 100-400 (P < .03) and S-f 20-100 (P < .05) and simi lar to malondealdehyde low-density lipoprotein (MDA-LDL). To assess th e mechanisms involved, the chemical composition and cellular degradati on of diabetic and control lipoproteins were compared. Postprandial di abetic S-f 100-400 had abnormal composition (phospholipid to protein r atio. 1.86 +/- 0.14 v 1.5 +/- 0.13, P < .05) and in preliminary experi ments demonstrated increased cell association (mean +/- SD at 6 hours, 126 +/- 34.3 v 57 +/- 4.2) and degradation (584 +/- 141 v 254 +/- 13) compared with that of normal controls, and may account for the observ ed increase in EC accumulation. In summary, postprandial diabetic S-f > 400 and S-f 100-400 TGRLP increase CE synthesis and S-f > 400, S-f 1 00-400, and S-f 20-100 lipoproteins increase EC accumulation in human macrophages compared with normal control lipoproteins. Diabetic S-f 10 0-400 lipoproteins have abnormal composition and seem to have increase d cellular association and degradation compared with normal lipoprotei ns. Our findings suggest a role for postprandial TGRLP in the increase d risk of cardiovascular disease among subjects with IDDM. Copyright ( C) 1994 by W.B. Saunders Company