Triglyceride-rich Lipoprotein Cholesterol Research Articles

The relationship between migraine and lipid sub-fractions among individuals without cardiovascular disease: A cross-sectional evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Introduction Recent studies have explored the relationship between dyslipidemia and migraine in a cardiovascular context. Thus, we aimed to evaluate the possible association between lipids, lipoprotein subfractions and migraine according to aura symptoms in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods 1,560 women and 1,595 men, without CVD or lipid disorders requiring medication, underwent a baseline clinical assessment. Total-cholesterol and its sub-fractions (LDL, VLDL and HDL subclass cholesterol); triglycerides and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL1+2-C VLDL3-C + IDL-C)] were determined by vertical auto profile (VAP). We also calculated logarithmic LDL density ratio [LLDR = ln ((LDL3-C + LDL4-C)/(LDL1-C + LDL2-C))], T-Chol/HDL-C and triglycerides/HDL-C ratios. Odds ratios (OR) with 95% confidence intervals (CI) were obtained to evaluate the relationship between lipids tertiles and migraine for both sexes. Results Main findings revealed positive associations between migraine without aura (MO) and the highest tertiles of VLDL-C (OR, 1.61; 95%CI, 1.07-2.40) and TRL-C (OR, 1.55; 95% CI, 1.03-2.34) in women. In men, the highest tertile of VLDL3-C (OR, 3.87; 95%CI, 1.23-12.19) was positively associated with MO, as well. Conclusions In middle-aged participants without CVD or lipid disorders requiring medication, the worst lipid profile was determined by the highest levels of TRL-C and their cholesterol-rich remnants in migraineurs without aura for both sexes.

Relation of Fasting Triglyceride-Rich Lipoprotein Cholesterol to Coronary Artery Calcium Score (from the ELSA-Brasil Study)

Although low-density lipoprotein cholesterol (LDL-C) is widely accepted as the principal lipid fraction associated with atherosclerosis, emerging evidence suggests a causal relation between lifelong elevations in triglyceride-rich lipoprotein cholesterol (TRL-C) and cardiovascular disease (CVD) in genetic studies. To provide further evidence for the potential relevance of TRL-C and atherosclerosis, we have evaluated the relation between TRL-C and coronary artery calcium (CAC) score. We included 3,845 subjects (49.9 ± 8.4years, 54% women) who had no history of CVD, were not using lipid-lowering medications, and underwent CAC evaluation. We assessed the relation between increasing fasting TRL-C and the graded increase in CAC and to what extent TRL-C were independently associated with CAC over and above LDL-C using logistic regression models. Overall, 973 (25%) of the participants had a CAC >0 and 308 (8%) had a CAC >100. The median TRL-C level was 22 mg/dL (IQR 16 to 32). Subjects with CAC >0 had higher TRL-C levels than thosewithCAC= 0 (p <0.001). Similarly, subjects with CAC >0 had higher levels of LDL-C, non-high-density lipoprotein cholesterol, and lower high-density lipoprotein cholesterol (all p<0.001). After multivariate adjustment, log-transformed TRL-C remained associated with the presence and severity of CAC (all p <0.05). When TRL-C was added to models that contained demographic factors and conventional lipids, it significantly improved the model to predict the presence of CAC >0 (p= 0.01). In conclusion, in a large cohort of asymptomatic subjects, TRL-C was associated with subclinical atherosclerosis supporting a potentially causal role in CVD.

The future of n-3 polyunsaturated fatty acid therapy.

This article focuses on the potential role by which a complex mixture of omega-3 fatty acids (OM3-FAs) may beneficially modify cardiovascular risk by modifying the cholesterol composition of atherogenic lipoproteins. This hypothesis is being tested in the STRENGTH trial, which is enrolling 13 000 patients on statins at high cardiovascular risk with hypertriglyceridemia and low HDL cholesterol (HDL-C) treated with an OM3-carboxylic acid. Complex mixtures of OM3-FAs containing predominately eicosapentanoic acid and docosahexanoic acid in combination with statins lowers non-HDL by reducing triglyceride-rich lipoprotein cholesterol (TRL-C) while shifting small LDL cholesterol (LDL-C) to large LDL-C. Recent genomic and epidemiological studies have implicated TRL-C and small LDL-C as causal for cardiovascular disease. Therefore OM3-FAs containing both eicosapentanoic acid and docosahexanoic acid in combination with statins may beneficially modify the high residual risk for patients with hypertriglyceridemia and low HDL-C. Although outcome trials are underway, subgroup analyses of data from previous randomized controlled trials are suggestive of a reduction in coronary artery disease and atherosclerotic cardiovascular disease event rates with triglyceride and TRL-C lowering therapies, particularly if accompanied by low HDL-C. Although the limitations of such data are acknowledged, clinicians must make treatment decisions while awaiting more definitive results from well-designed large-scale randomized controlled trials.

Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia.

The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin.

PITAVASTATIN REDUCES REMNANT LIPOPROTEIN CHOLESTEROL SIGNIFICANTLY MORE THAN DOES PRAVASTATIN IN HIV-INFECTED SUBJECTS: THE INTREPID TRIAL

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in those with chronic HIV infection, due in part to HIV associated dyslipidemia. An emerging CVD risk factor is triglyceride-rich remnant lipoprotein cholesterol (RLP-C: the sum of IDL and VLDL3 cholesterol). The effects of

Novel unbiased equations to calculate triglyceride-rich lipoprotein cholesterol from routine non-fasting lipids

BackgroundNon-fasting triglyceride-rich lipoproteins cholesterol (TRL-C) contributes to cardiovascular risk, in that it includes remnant cholesterol (RC). TRL-C is computed as total C - [LDL-C + HDL-C]. Such calculation applies only if LDL-C is directly measured, or obtained from a non-Friedewald’s formula, a method as yet never benchmarked against independent markers of TRL burden.MethodsThe Discriminant Ratio (DR) methodology was used in 120 type 2 diabetic patients in order: (i) to compute TRL-C from non-fasting lipids; (ii) to establish the performance of TRL-C and TRL-C/apoA-I (vs. TG-based markers) to grade TRLs and atherogenic dyslipidemia (AD); and (iii) to relate TRL-C with non-fasting TG.ResultsDepending on apoB100 availability, TRL-C (mg/dL) can be derived from non-fasting lipids in two ways: (a) total cholesterol (TC) - [(0.0106 * TC - 0.0036 * TG + 0.017 * apoB100 - 0.27) * 38.6] - HDL-C; and (b) TC - [(0.0106 * TC - 0.0036 * TG + 0.017 * [0.65 * (TC - HDL-C) + 6.3] - 0.27) * 38.6] - HDL-C. Discrimination between log[TG] and TRL-C was similar (DR 0.94 and 0.84, respectively), whereas that of log[TG]/HDL-C was better than TRL-C/apoA-I (DR 1.01 vs. 0.65; p 0.0482). All Pearson’s correlations between pairs reached unity, allowing formulation of two unbiased equivalence equations: (a) TRL-C = 97.8 * log[TG] - 181.9; and (b) TRL-C/apoA-I = 8.15 * (log[TG]/HDL-C) - 0.18.ConclusionsTRL-C and log[TG] are as effective and interchangeable for assessing remnant atherogenic particles. For grading TRL-AD, it is best to use log[TG]/HDL-C, inherently superior to TRL-C/apoA-I, while measuring the same underlying variable.

Abstract 18730: Correlates and Cut-points of the Triglyceride/HDL Cholesterol Ratio: The Very Large Database of Lipids 4 (VLDL-4)

Background: An elevated TG/HDL-C is predictive of atherosclerotic cardiovascular disease; however, advanced lipoprotein correlates of the TG/HDL-C ratio and discrimination by standard cut-points are incompletely characterized. Hypothesis: Elevated TG/HDL-C correlates most strongly with triglyceride-rich remnant lipoprotein cholesterol (RLP-C) and also with LDL density, Lp(a)-C, and male gender. Methods: We examined 1,350,908 individuals from the Very Large Database of Lipids (Baltimore, MD; NCT01698489 ) who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL). LDL density was assessed as a continuous LDL density parameter (LLDR) calculated as the natural log of the ratio of dense to buoyant LDL-C subfractions. RLP-C was defined as VLDL 3 -C plus IDL-C. Results: The strongest univariate correlates of the TG/HDL-C ratio were VLDL 3 -C (spearman rho= 0.824, p&lt;0.0001) and IDL-C (spearman rho=0.537, p&lt;0.0001). In a multivariable linear regression model including age, gender, LLDR, Lp(a)-C, VLDL 3 -C, and IDL-C, the overall adjusted R 2 was 0.764 (p&lt;0.0001). In this model, IDL-C was inversely correlated (partial R=-0.140, p&lt;0.0001) while VLDL 3 -C (partial R=0.697, p&lt;0.001) was more strongly and positively associated with TG/HDL-C. We compared demographic and lipid parameters across standard cut-points of TG/HDL-C (&lt;3, 3-5, &gt;5) ( Table ). Compared with the TG/HDL-C &lt;3 group, there was a 36% higher VLDL 3 -C level in those with a TG/HDL-C of 3-5, and 73% higher level in those with a TG/HDL-C &gt;5. There was a progressively higher LLDR across these groups characteristic of increasing LDL density. Conclusions: A higher TG/HDL ratio is correlated with an increasingly atherogenic lipid phenotype. Across increasing TG/HDL-C groups, VLDL 3 -C, IDL-C, and RLP-C increase. Non-HDL-C rises across these groups along with LDL density, despite similar LDL-C.

Intensive Glucose Lowering and Cardiovascular Disease Prevention in Diabetes

Cardiovascular disease (CVD) is a very common, if not the most common, cause of morbidity and mortality in developed countries, and there has been longstanding recognition that diabetes is a potent risk factor for CVD.1,–,3 Individuals with either type 1 or type 2 diabetes mellitus manifest CVD rates up to 4 to 10 times higher than those observed in nondiabetic subjects. Subjects with diabetes also have been shown to have more advanced atherosclerosis, as measured by carotid intima-media thickness (CIMT) measures or coronary artery calcium (CAC) scores.4,–,7 The potential pathophysiology of accelerated atherosclerosis and CVD risk in diabetes is complex8 (Table 1). Patients with type 2 diabetes mellitus commonly have hypertension and manifest a number of abnormalities in systemic lipoprotein metabolism and in inflammatory and coagulation pathways that are predicted to be proatherogenic and to increase CVD risk on the basis of observational and mechanistic studies conducted in diabetic and nondiabetic experimental models. These abnormalities are related to coexisting insulin resistance in the majority of patients with diabetes and manifest as low high-density lipoprotein cholesterol, increased triglyceride-rich lipoprotein cholesterol, postprandial lipemia, elevated levels of C-reactive protein and other inflammatory markers, and increased levels of plasminogen activator inhibitor 1 and fibrinogen levels. Insulin resistance in patients with type 2 diabetes mellitus is generally but not always related to obesity and may be more specifically linked to central obesity and accumulation of fat in the visceral fat depot.9,10 View this table: Table 1. Potential Contributors to Accelerated Atherosclerosis and CVD in Diabetes In patients with type 1 diabetes mellitus, understanding of the potential pathophysiologies for accelerated atherosclerosis and CVD is complicated by the young age (usually before the second or third decade of life) of these patients at the time of diagnosis of …

Hypertriglyceridemic Waist Phenotype Predicts Increased Visceral Fat in Subjects With Type 2 Diabetes

OBJECTIVEGreater accumulation of visceral fat is strongly linked to risk of cardiovascular disease. However, elevated waist circumference by itself does not always identify individuals with increased visceral fat.RESEARCH DESIGN AND METHODSWe examined 375 subjects with type 2 diabetes from the CHICAGO cohort for presence of hypertriglyceridemic waist phenotype (waist circumference >90 cm in men or >85 cm in women, in conjunction with a plasma triglyceride concentration of ≥177 mg/dl) to determine its usefulness for identifying subjects with increased amounts of visceral fat. We divided subjects into three groups: group 1 (low waist circumference and low triglycerides; waist circumference ≤90 cm in men or ≤85 cm in women and triglyceride <177 mg/dl, n = 18), group 2 (high waist circumference and low triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides <177 mg/dl, n = 230), and group 3 (high waist circumference and high triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides ≥177 mg/dl, n = 127).RESULTSSubjects in group 3 had significantly higher visceral fat (P < 0.0001), A1C (P < 0.01), and coronary artery calcium (P < 0.05) compared with group 2, despite similar age, BMI, and waist circumference. The relationship of the phenotype to atherosclerosis, however, was attenuated by adjustment for HDL cholesterol, triglyceride-rich lipoprotein cholesterol, apolipoprotein B, or LDL particle number.CONCLUSIONSThe presence of hypertriglyceridemic waist phenotype in subjects with type 2 diabetes identifies a subset with greater degree of visceral adiposity. This subset also has greater degree of subclinical atherosclerosis that may be related to the proatherogenic lipoprotein changes.

Relationship of Traditional and Nontraditional Cardiovascular Risk Factors to Coronary Artery Calcium in Type 2 Diabetes

We evaluated correlates of coronary atherosclerosis, measured by coronary artery calcium, in a racially diverse group of male and female subjects with type 2 diabetes. Age, systolic blood pressure, sex, and race/ethnicity were significant determinants of coronary artery calcium. Among lipoproteins, cholesterol level contained in a particle excluded from direct measures of LDL and HDL cholesterol (designated triglyceride-rich lipoprotein cholesterol) was most strongly linked to coronary artery calcium. Neither inflammatory markers nor metabolic factors correlated with coronary artery calcium in models adjusted for age and sex, but measures of adipose distribution did. Waist-to-hip ratio and the ratio of visceral to total abdominal tissue were positively associated with coronary artery calcium. In fully adjusted multivariate models, the relationship of adiposity measures to coronary artery calcium was no longer significant after inclusion of apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Traditional risk factors and race/ethnicity remain important correlates of coronary artery calcium in a cohort at elevated risk of cardiovascular disease because of type 2 diabetes. Adiposity measures are significantly associated with coronary artery calcium score, but their importance may be largely explained by apolipoprotein B or triglyceride-rich lipoprotein cholesterol.

The Plasma and Lipoprotein Triglyceride Postprandial Response to a Carbohydrate Tolerance Test Differs in Lean and Massively Obese Normolipidemic Women

The goal of the present study was to compare the plasma lipid responses of massively obese and lean women to a fat load and a carbohydrate load. For this purpose, 11 lean [body mass index (BMI), 21.6 +/- 2 kg/m(2)] and 8 obese (BMI, 50.8 +/- 7 kg/m(2)) normolipidemic women were given, in random order, either a dietary carbohydrate load (3.43 MJ, 166 g carbohydrates, 38 g proteins) or a dietary fat load (3.35 MJ, 70 g fat, 36 g proteins). Blood samples were collected hourly for 9 h after the test meal for measurements of triglyceride-rich lipoprotein (TRL)-lipid, apolipoprotein (apo)B-48 and apoB-100. Triglycerides (P < 0.0001), TRL triglycerides (P < 0.0001), TRL cholesterol (P < 0.04) and apoB-48 (P < 0.0001) peaked 3 h after the fat meal and returned progressively to baseline values in both obese women and lean controls. These lipid and apolipoprotein changes did not differ between the two groups. In contrast, after the carbohydrate load, the plasma triglyceride (P < 0.0001) and TRL triglyceride (P < 0.0001) increments were significantly greater in obese women than in lean controls. This carbohydrate-induced TRL triglyceride increment was half of that following the isocaloric fat load. The carbohydrate load did not affect apoB-100 and apoB-48 levels. These findings suggest that postprandial triglyceride metabolism is impaired after a carbohydrate load in normolipidemic massively obese women.

Inactive Lipoprotein Lipase (LPL) Alone Increases Selective Cholesterol Ester Uptake in Vivo, Whereas in the Presence of Active LPL It Also Increases Triglyceride Hydrolysis and Whole Particle Lipoprotein Uptake

We have previously shown that transgenic expression of catalytically inactive lipoprotein lipase (LPL) in muscle (Mck-N-LPL) enhances triglyceride hydrolysis as well as whole particle lipoprotein and selective cholesterol ester uptake. In the current study, we have examined whether these functions can be performed by inactive LPL alone or require the presence of active LPL expressed in the same tissue. To study inactive LPL in the presence of active LPL in the same tissue, the Mck-N-LPL transgene was bred onto the heterozygous LPL-deficient (LPL1) background. At 18 h of age, Mck-N-LPL reduced triglycerides by 35% and markedly increased muscle lipid droplets. In adult mice, it reduced triglycerides by 40% and increased lipoprotein particle uptake into muscle by 60% and cholesterol ester uptake by 110%. To study inactive LPL alone, the Mck-N-LPL transgene was bred onto the LPL-deficient (LPL0) background. These mice die at approximately 24 h of age. At 18 h of age, in the absence of active LPL, inactive LPL expression did not diminish triglycerides nor did it result in the accumulation of muscle lipid droplets. To study inactive LPL in the absence of active LPL in the same tissue in adult animals, the Mck-N-LPL transgene was bred onto mice that only expressed active LPL in the heart (LPL0/He-LPL). In this case, Mck-N-LPL did not reduce triglycerides or increase the uptake of lipoprotein particles but did increase muscle uptake of chylomicron and very low density lipoprotein cholesterol ester by 40%. Thus, in the presence of active LPL in the same tissue, inactive LPL augments triglyceride hydrolysis and increases whole particle triglyceride-rich lipoprotein and selective cholesterol ester uptake. In the absence of active LPL in the same tissue, inactive LPL only mediates selective cholesterol ester uptake.

Triglyceride-rich lipoprotein cholesterol exceeds low-density lipoprotein cholesterol in hypertriglyceridemia patients.

The atherogenicity of triglyceride-rich lipoprotein has been revealed. This study was performed to explore the clinical importance of triglyceride-rich lipoprotein by measuring its cholesterol content and comparing it with other lipoprotein fractions. Blood samples were obtained from 103 patients whose fasting plasma triglyceride concentration exceeded 300 mg/dl. The cholesterol monitor using the technique of high-performance liquid chromatography was used for the measurement of their plasma cholesterol concentrations and the determination of cholesterol distribution among lipoprotein fractions. This monitor showed 4 peaks: large-triglyceride-rich lipoprotein, small-triglyceride-rich lipoprotein, low-density lipoprotein, and high-density lipoprotein. Total cholesterol increased with increasing triglyceride. The increment of total cholesterol was nearly equal to that of small-triglyceride-rich lipoprotein cholesterol. Small-triglyceride-rich lipoprotein cholesterol exceeded low-density lipoprotein cholesterol where plasma triglyceride concentration was over 500 mg/dl. In conclusion, triglyceride-rich lipoprotein may be clinically important for hypertriglyceridemic patients as a source of cholesteryl ester in arteriosclerotic plaques, and increased triglyceride-rich lipoprotein cholesterol may be used as a basis for hypertriglyceridemia atherogenicity. Our study suggests that hypertriglyceridemia should be treated to prevent arteriosclerotic disease.

Whole Wheat and Triticale Flours with Differing Viscosities Stimulate Cecal Fermentations and Lower Plasma and Hepatic Lipids in Rats

Whole flours from oat, rye or barley effectively modify digestive fermentation and lipid metabolism, whereas the effectiveness of whole wheat flour has not been established. To address this question, cecal digestion, short-chain fatty acid (SCFA) metabolism and cholesterol metabolism were investigated in four groups of rats fed the following semipurified diets differing in their carbohydrate source: a control diet (purified wheat starch) and three whole cereal flour diets [Valoris wheat (Wv), Soissons wheat (Ws), or Carnac triticale (Tc)]. Wv is particularly viscous and rich in arabinoxylans, and Tc is richer in hemicellulose than wheat. Compared with controls, rats fed the whole-flour diets had enlarged ceca and a moderate acidification of the bulk pH ( approximately 6.4). In these rats, the cecal SCFA pool size was enhanced (P < 0.05), and the SCFA molar ratio reflected propionic/butyric acid-rich fermentations, especially in those fed TC: The portal SCFA concentrations reflected the rise of the acetic and propionic acid pools in the cecum, whereas portal butyric acid remained relatively low, probably reflecting extensive metabolism by the cecal wall. The fecal excretion of total steroids (bile acids + sterols) was markedly enhanced by all of the whole-flour diets, with Wv (+78%) > Tc (+64%) > Ws (+47%). In parallel, there was a significant plasma cholesterol-lowering effect for rats fed Wv (-27%) and Tc (-32%) and a plasma triglyceride-lowering effect (approximately -40%) in all rats fed whole-flour diets (P < 0.05). This effect was observed mainly for triglyceride-rich lipoprotein-cholesterol, whereas HDL cholesterol was unaffected. These results indicate that whole wheat flours can strikingly affect cecal SCFA, especially butyrate, and are effective plasma cholesterol-lowering agents.

Amphotericin B lipid complex or amphotericin B multiple-dose administration to rabbits with elevated plasma cholesterol levels: pharmacokinetics in plasma and blood, plasma lipoprotein levels, distribution in tissues, and renal toxicities.

The purpose of the present study was to determine if a relationship exists between the plasma cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the pharmacokinetics of AmpB in plasma in hypercholesterolemic rabbits administered multiple doses of amphotericin B (AmB) deoxycholate (Doc-AmB) and AmB lipid complex (ABLC). After 7 days of administration of a cholesterol-enriched diet (0.50% [wt/vol]) or a regular rabbit diet, each rabbit was administered a single intravenous bolus of Doc-AmB (n = 8) or ABLC (n = 10) (1.0 mg/kg of body weight) daily for 7 consecutive days (a total of eight doses). Blood samples were obtained daily before and 24 h after the administration of each dose and serially thereafter following the administration of the last dose for the assessment of pharmacokinetics in plasma, kidney toxicity, plasma lipoprotein levels, and drug distribution in tissue. The pharmacokinetics of AmB in blood following the administration of ABLC were also determined in rabbits fed cholesterol-enriched and regular diets (n = 3 each group). Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total, low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) cholesterol levels in plasma compared with the levels in rabbits on a regular diet. No significant differences in total plasma triglyceride levels were observed. Significant increases in plasma creatinine levels were observed in rabbits fed a cholesterol-enriched diet (P < 0.05) and rabbits fed a regular diet (P < 0.05) when administered AmB. However, the magnitude of this increase was twofold greater in rabbits fed a regular diet than in rabbits fed a cholesterol-enriched diet. An increase in plasma creatinine levels was observed only in rabbits on a cholesterol-enriched diet administered ABLC. The pharmacokinetics of AmB were significantly altered in rabbits on a cholesterol-enriched diet administered Doc-AmB or ABLC compared to those in rabbits on a regular diet administered each of these compounds. The pharmacokinetics of AmB in blood were significantly different following ABLC administration but not following Doc-AmB administration in both rabbits fed cholesterol-enriched diets and rabbits fed regular diets compared to their corresponding pharmacokinetics in plasma. An increased percentage of AmB was recovered in the TRL fraction when Doc-AmB was administered to rabbits fed a cholesterol-enriched diet than when it was administered to rabbits fed a regular diet. Furthermore, an increased percentage of AmB was recovered in the LDL and TRL fractions when ABLC was administered to rabbits fed a cholesterol-enriched diet rabbits fed a regular diet. These findings suggest that an increase in plasma cholesterol levels modifies the pharmacokinetics of AmB and renal toxicity following the administration of multiple intravenous doses of Doc-AmB and ABLC.

Alterations in apolipoprotein B-48 in the postprandial state in NIDDM

The intestine is a major site of cholesterol synthesis and produces apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density < 1.006 g/ml). Apolipoprotein B-48 was separated on 4-15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the triglyceride-rich lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial triglyceride-rich apolipoprotein B-48 profile significantly different from that of control subjects (p < 0.05). The triglyceride and total protein concentration in the triglyceride-rich lipoprotein fraction mirrored the post-prandial profile and apolipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p < 0.02) and total protein (p < 0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial triglyceride-rich lipoprotein cholesterol and total apolipoprotein B were significantly higher in diabetic patients than in control subjects (p < 0.05). Since apolipoprotein B-48 is the structural protein of intestinally-derived lipoprotein particles, these studies suggest an abnormality in intestinal lipoprotein metabolism in diabetes.