Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease.

The aim of the present cross-sectional angiographic study was to examine if there is a relationship between the severity of CAD and postprandial lipemia in patients with type 2 diabetes mellitus. Special emphasis was directed to determining the contribution of apolipoprotein B-48 (apoB-48)-containing and B-100 (apoB-100)-containing triglyceride-rich particles to the magnitude of postprandial lipemia and degree of CAD. The role of apolipoprotein E (apoE) phenotype as a modulator of postprandial lipemia was also evaluated. The severity of CAD was determined by a quantitative coronary angiography and the subjects were classified into two groups based on the presence (severe CAD) or absence (mild CAD) of at least 50% stenosis in a major coronary vessel. The study population consisted of 43 subjects (31 men and 12 women) with fair glycemic control and comparable fasting lipids and body mass index. Postprandial responses of TG, apoB-48 and apoB-100 in lipoprotein subfractions (chylomicrons, VLDL1, VLDL2 and IDL) were determined after a fat load. Type 2 diabetic patients exhibited the classical dyslipidemia of the insulin resistance syndrome and delayed clearance of both hepatic and intestinal particles. Fasting or postprandial lipid or lipoprotein measurements, including apoB-48 and apoB-100 concentrations, did not differ between the groups. The presence or absence of apoE-4 allele did not significantly influence postprandial lipemia. The severity of the most significant coronary stenosis in angiography correlated with plasma and with chylomicron area under curve (AUC) for TG (n=27) and chylomicron AUC for apoB-48 (n=20). The strongest correlate of maximal stenosis was area under incremental curve (AUIC) for apoB-100 in IDL fraction (r=0.548, P=0. 012, n=20). In conclusion, postprandial apoB-48 and apoB-100 metabolism in triglyceride rich lipoproteins is distorted in type 2 diabetic patients, even in those with only mild CAD. The data suggest that postprandial change in small remnant particle numbers may contribute to the severity of CAD in type 2 diabetes.

Delayed clearance of postprandial large TG-rich particles in normolipidemic carriers of LPL Asn291Ser gene variant.

The carrier frequency of Asn291Ser polymorphism of the lipoprotein lipase (LPL) gene is 4;-6% in the Western population. Heterozygotes are prone to fasting hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol concentrations especially when secondary factors are superimposed on the genetic defect. We studied the LPL Asn291Ser gene variant as a modulator of postprandial lipemia in heterozygote carriers. Ten normolipidemic carriers were compared to ten control subjects, who were selected to have similar age, sex, BMI, and apolipoprotein (apo)E-phenotype. The subjects were given a lipid-rich mixed meal and their insulin sensitivity was determined by euglycemic hyperinsulinemic clamp technique. The two groups had comparable fasting triglycerides and glucose utilization rate during insulin infusion, but fasting HDL cholesterol was lower in carriers (1.25 +/- 0.05 mmol/L) than in the control subjects (1. 53 +/- 0.06 mmol/L, P = 0.005). In the postprandial state the most pronounced differences were found in the very low density lipoprotein 1 (VLDL1) fraction, where the carriers displayed higher responses of apoB-48 area under the curve (AUC), apoB-100 AUC, triglyceride AUC, and retinyl ester AUC than the control subjects. The most marked differences in apoB-48 and apoB-100 concentrations were observed late in the postprandial period (9 and 12 h), demonstrating delayed clearance of triglyceride-rich particles of both hepatic and intestinal origin. Postprandially, the carriers exhibited enrichment of triglycerides in HDL fraction. Thus, in normolipidemic carriers the LPL Asn291Ser gene variant delays postprandial triglyceride, apoB-48, apoB-100, and retinyl ester metabolism in VLDL1 fraction and alters postprandial HDL composition compared to matched non-carriers.

Decreased postprandial high density lipoprotein cholesterol and apolipoproteins A-I and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities.

We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.

Comparison of three fatty meals in healthy normolipidaemic men: high post-prandial retinyl ester response to soybean oil.

BACKGROUND: Oral fat tolerance tests (FTTs) have been widely used as a tool to investigate post-prandial lipaemia. However, there is no consensus regarding the type and amount of fat used in the tests. METHODS: We compared three commonly used FTTs, each containing 63 g of fat: a mixed meal, a liquid cream meal and a liquid soybean oil meal. The study group consisted of 10 healthy normolipidaemic men. We measured triglycerides (TGs), retinyl esters (REs), apolipoprotein E (apoE), apolipoprotein B-48 (apoB-48) and apolipoprotein B-100 (apoB-100) in plasma and in triglyceride-rich lipoprotein (TRL) fractions separated by density-gradient ultracentrifugation at baseline and 3, 4, 6, and 8 h after the FTTs. RESULTS: We observed similar TGs, apoE, apoB-48 and apoB-100 responses after all three FTTs, despite the different fatty acid composition of the meals. In contrast, the commonly used marker for exogenous particles, RE, differed clearly when polyunsaturated (soybean oil) and saturated fat (cream or mixed meal) were used. The RE response in plasma (P < 0.005, repeated measures ANOVA), in chylomicrons (P < 0.013) and in very low-density lipoprotein (VLDL) 1 (P < 0.017), as well as the RE area under the incremental curve in plasma and chylomicron fractions, were markedly increased after the soybean oil meal compared with the mixed meal and cream meal tests. The peak of RE response occurred parallel to the responses of other markers (i.e. TG or apoB-48) of post-prandial TRL during soybean oil meal. In contrast, RE peak concentration was delayed after saturated fat-containing meals. After soybean oil, FTT plasma cholesterol concentration was lower and the chylomicron cholesterol concentration was higher compared with mixed or cream meals, but no differences were detected in post-prandial high-density lipoprotein (HDL)-cholesterol concentration. CONCLUSION: When the amount of fat is similar, post-prandial responses of TG, apoE, apoB-48, apoB-100 and HDL-cholesterol were comparable after different FTTs.

Postprandial lipid metabolism in diabetes.

Postprandial lipemia is an inherent feature of diabetic dyslipidemia and highly prevalent in diabetic patients even with normal fasting triglyceride concentrations. Postprandial lipemia is characterized by long residence time of chylomicron and VLDL remnants in the circulation. Insulin resistance causes increased flux of free fatty acids, and thus enhanced VLDL apolipoprotein B (apo B) synthesis in the liver. Together with chylomicron and VLDL remnant competition for the common removal mechanisms the increased substrate input results in exaggerated and prolonged postprandial lipemia. Studies using both apo B-48 and retinyl esters as a marker for intestinally derived particles have shown that increased postprandial lipemia does not predict the presence or absence of coronary artery disease between non-insulin-dependent diabetes mellitus (NIDDM) subjects. Recent data have shown that postprandial triglyceride-rich remnants are atherogenic, and postprandial hypertriglyceridemia contributes to the metabolic disturbances transforming LDL and HDL subclasses into more atherogenic direction in diabetic subjects.

Postprandial elevation of ApoB-48-containing triglyceride-rich particles and retinyl esters in normolipemic males who smoke.

Smokers have an increased risk for coronary artery disease (CAD), which can only partly be explained by fasting lipoprotein changes. Recent studies have indicated that smokers express metabolic abnormalities characteristic of insulin resistance syndrome. A preliminary study reported an increased postprandial triglyceride (TG) response in smokers compared with nonsmokers. To investigate the effect of smoking on postprandial lipemia, a fat-rich mixed meal (837 kcal, 63 g of fat) was served to 12 healthy smokers and 12 controls with similar fasting lipoprotein profiles, body composition, and lifestyles. Blood was drawn before and 3, 4, 6, and 8 hours postprandially, and triglyceride-rich lipoprotein (TRL) fractions (chylomicrons, VLDL1, VLDL2, and IDL) were separated with density gradient ultracentrifugation. Pre- and postprandial TG, retinyl esters (RE), apolipoprotein B-48 (apoB-48) and B-100 (apoB-100) were measured in each fraction. Smokers showed a significantly increased postprandial TG response in chylomicrons, VLDL1, and VLDL2. The areas under the incremental curve (AUIC) of apoB-48 in chylomicrons (2.83 +/- 0.84 versus 0.56 +/- 0.17; P < .05) and VLDL1 (10.17 +/- 1.96 versus 2.95 +/- 2.44; P = < .01) were markedly higher in smokers than in controls. Changes of RE responses of all TRL fractions were consistent with those of apoB-48. Postprandial apoB-100 concentrations and lipolytic enzymes were similar between the two groups. In conclusion, smokers have the syndrome of impaired TG tolerance because of defective clearance of chylomicrons and their remnants. Prolonged residence time of atherogenic remnant particles may constitute a significant risk factor for CAD in smokers.

The insulin resistance syndrome and postprandial lipid intolerance in smokers.

BACKGROUND: The effects of cigarette smoking on insulin resistance, postprandial lipemia following a mixed meal, lipoproteins and other aspects of the insulin resistance syndrome (IRS) were investigated in healthy middle-aged men. METHODS: 36 smoking and 25 age- and body mass index (BMI)-matched non-smoking men participated. They were non-obese (BMI < 27), healthy and without any medication. The smokers had been smoking more than 10 cigarettes per day for more than 20 years; the non-smokers had never been habitual smokers. Body composition and several metabolic and cardiovascular risk factors were studied, including the prevalence of small dense LDL-particles, lipoprotein and hepatic lipase activity and triglyceride levels after a mixed test meal. For determination of degree of insulin sensitivity the euglycemic hyperinsulinemic clamp technique was used. RESULTS: The smokers had lower HDL-cholesterol and lipoprotein A-I levels but higher fasting triglycerides, as well as an increased proportion of small dense LDL-particles and higher postheparin hepatic lipase activity. They also had higher levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1) activity and fasting and steady-state C-peptide levels during the clamp. The smokers were insulin resistant and lipid intolerant with an impaired triglyceride clearance after a mixed test meal. This lipid intolerance was not mirrored by fasting hypertriglyceridemia. CONCLUSIONS: This study, using the euglycemic hyperinsulinemic clamp technique, shows that smokers are both insulin resistant and lipid intolerant. The postprandial lipid intolerance is also seen in individuals with normal fasting triglyceride levels and is related to an increased prevalence of atherogenic small dense LDL. IRS is likely to be an important reason for the increased cardiovascular morbidity in smokers.