FASTING AND POSTPRANDIAL DETERMINANTS FOR THE OCCURRENCE OF SMALL DENSE LDL SPECIES IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH AND WITHOUT HYPERTRIGLYCERIDEMIA - THE INVOLVEMENT OF INSULIN, INSULIN PRECURSOR SPECIES AND INSULIN-RESISTANCE

We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandia l triglyceride (TG)rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:c holesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intest inal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a pr eponderance of small dense LDL particles present in the plasma and red uced amounts of large buoyant species when compared to normotriglyceri daemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concent rations of proinsulin (P < 0.05), although insulin content did not dif fer significantly. 32-33 split proinsulin (SPI) was the major insulin- like molecule present in HTG and was present in significantly higher a mounts in these patients (P < 0.05) than either NTG or control subject s and correlated significantly with the presence of small dense LDL pa rticles, After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylo micron remnants were present to a greater extent in HTG than in NTG an d controls (P < 0.05), although in this case NTG also contained more c hylomicron remnants than control subjects (P < 0.05). There was no dif ference in the LPL activity, CETP and LCAT between diabetics and contr ols, whereas an increase in hepatic lipase activity was seen in the HT G diabetics (P < 0.05). Both CETP and LCAT activities increased postpr andially. Multivariate analysis showed that TG, HDL content and HL act ivity were the most important determinants of small dense LDL concentr ation in the fasting state (R(2) = 67%). Postprandially, chylomicron r emnant clearance, HL and insulin resistance were the major determinant s (R(2) = 61%) Of LDL-III.