Postprandial lipoprotein metabolism may be important in atherogenesis and has not been studied in detail in noninsulin-dependent diabetes mellitus (NIDDM). We used the vitamin A fat-loading test to label triglyceride-rich lipoprotein particles of intestinal origin after ingestion of a high fat mixed meal containing 60 g fat/m2 and 60,000 U vitamin A/m2 in 12 untreated NIDDM subjects with normotriglyceridemia (NTG; triglycerides, less than 1.7 mmol/L), 7 untreated NIDDM subjects with moderate hypertriglyceridemia (HTG; triglycerides, 1.7-4.7 mmol/L), and 8 age- and weight-matched normotriglyceridemic nondiabetic controls. The postprandial triglyceride increment was greater in NIDDM with HTG (P = 0.0001) and correlated strongly in all groups with the fasting triglyceride concentration (r = 0.83; P = 0.0001). Retinyl palmitate measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction was also significantly greater in NIDDM with HTG, but did not differ significantly between NIDDM with NTG and controls. In NIDDM with HTG, chylomicrons appeared to be cleared at a slower rate, as evidenced by the significantly later intersection of the chylomicron and nonchylomicron retinyl palmitate response curves (13.7 h in HTG NIDDM vs. 8.5 h in NTG NIDDM vs. 7.3 h in controls; P less than 0.01). Although fasting FFA levels were similar in all three groups, the HTG diabetic subjects had a late postprandial surge in FFAs that lasted for up to 14 h. The postprandial FFA elevation in all groups correlated with the fasting triglyceride concentration (r = 0.57; P less than 0.002) and postprandial triglyceride increment (r = 0.80; P = 0.0001). The fasting core triglyceride content of the HDL particles in NIDDM with HTG was significantly elevated compared to those in NIDDM with NTG and controls (21.0% vs. 14.0% vs. 14.1% respectively; P less than 0.05), and this increased proportionately in all groups after the meal at the expense of cholesteryl ester, the increase correlating with total plasma postprandial triglyceride increment (r = 0.51; P less than 0.01). We conclude that moderate fasting hypertriglyceridemia in NIDDM is predictive of a constellation of postprandial changes in lipids and lipoproteins that may potentiate the already unfavorable atherogenic fasting lipid profile in these subjects.

Abnormalities in fasting lipid and lipoprotein levels are known to occur in obesity and other hyperinsulinemic states. However, postprandial lipoprotein metabolism has not been studied systematically in obese subjects using sensitive techniques to distinguish between triglyceride-rich lipoprotein particles derived from the intestine and the liver. In the present study the vitamin A fat-loading test was used to label intestinally derived triglyceride-rich lipoprotein particles in the postprandial state. Lipid parameters in seven normolipidemic obese subjects [body mass index, 43.7 +/- 2.81 kg/m2 (mean +/- SEM)] were compared to those in eight matched normal weight controls (body mass index, 23.6 +/- 0.72 kg/m2) during the 24-h period following ingestion of a mixed meal with a high fat content to which vitamin A had been added. Although subjects were selected for normal fasting lipid levels, in the obese group fasting triglycerides were significantly higher (1.35 +/- 0.12 vs. 0.68 +/- 0.08 mmol/L; P less than 0.0005) and high density lipoprotein (HDL) cholesterol was lower (0.94 +/- 0.08 vs. 1.35 +/- 0.11 mmol/L; P less than 0.01). The obese subjects had a greater postprandial triglyceride response to the test meal (P less than 0.05). The cumulative increment in total plasma triglycerides was 3.35-fold greater in obese than control subjects, while that of retinyl ester was only 1.63-fold greater, suggesting that a significant portion of the postprandial triglyceride response is due to endogenous hepatic lipoproteins. Postprandial plasma triglyceride and retinyl ester increment correlated with basal triglycerides (r = 0.72; P less than 0.005 and r = 0.57; P less than 0.03, respectively) and negatively with fasting HDL (r = -0.51; P less than 0.05 and r = -0.60; P less than 0.02, respectively). In the obese, the HDL triglyceride content increased maximally 4 h postprandially (4.1% to 6.1%; P less than 0.005) and phospholipid at 12 h (25.8% to 28.7%; P less than 0.05), with lower cholesteryl ester (21.1% to 17.5%; P less than 0.002) at 8 h, reflecting exchange of surface and core lipids with triglyceride-rich particles after the meal. In obese and control subjects the magnitude of HDL triglyceride enrichment after the meal correlated positively with the postprandial triglyceride increment (r = 0.74; P less than 0.007) and negatively with the fasting HDL cholesterol concentration (r = -0.80; P = 0.002). We conclude that even normolipidemic obese subjects have greater postprandial lipemia and triglyceride enrichment of HDL after ingestion of a high fat meal.(ABSTRACT TRUNCATED AT 400 WORDS)

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