Abnormal clearance of postprandial S(f) 100-400 plasma lipoproteins in insulin-dependent diabetes mellitus

Studies were carried out in three normolipidemic non-obese men with insulin-dependent diabetes mellitus (IDDM) and three normal men, to assess whether the clearance of postprandial S(f) 100-400 lipoproteins is decreased in IDDM. S(f) > 100 lipoproteins isolated from plasma 4.5 h after fat ingestion were labeled with ¹²⁵I and injected into the same subject intravenously. ApoB radioactivity was measured over time in S(f) > 400, S(f) 100-400, and S(f) 20-100 lipoproteins isolated from plasma and analyzed using a kinetic model that included both fast and slow delipidation cascades, where lipolysis and uptake of particles by the liver and other tissues were represented. Fractional catabolic rates of S(f) 100-400 lipoproteins (min^-1) were decreased in diabetic versus control subjects: fast = 0.170 ± 0.126 versus 0.680 ± 0.242 (mean ± SD) (P < 0.05, two-tailed) and slow = 0.011 ± 0.006 versus 0.031 ± 0.015 (P < 0.05, one-tailed). Kinetic analysis showed that the data were consistent with decreased uptake by the tissues for the fast cascade (diabetic, 0.084 ± 0.082, vs. control, 0.617 ± 0.328, P < 0.05, one-tailed). A similar trend was observed for the slow cascade. There were no significant differences between the two groups in the intraplasma lipolysis rates of S(f) 100-400 particles. Analysis of the composition of the injected particles showed that they were total cholesterol (TC)- versus triglyceride (TG)-enriched (P < 0.001, log-ratio analysis of composition) in IDDM subjects. In conclusion, the decreased clearance of postprandial S(f) 100-400 lipoproteins in IDDM men appears to result from decreased tissue uptake (fast cascade) rather than impaired lipolysis, and may be related to cholesterol enrichment.