Postprandial Dyslipidemia Research Articles

Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial

The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Effect of a mixed meal on plasma lipids, insulin resistance and systemic inflammation in non-obese Indian adults with normal glucose tolerance and treatment naïve type-2 diabetes

AimAsian Indians are believed to have a lower capacity to clear a glucose load even during normoglycemia. High post meal glucose levels have been linked to postprandial dyslipidemia and generation of proinflammatory cytokines. Since humans spend most of their time in the postprandial state, the present study aims to evaluate the relationship of insulin resistance (IR) in the basal state with dyslipidemia and systemic inflammation (hs-CRP, IL-6 and TNF-a), in the fasting state, 2h and 4h after a mixed meal, in Indian adults with normal glucose tolerance, and new onset type-2 diabetes. MethodsForty-eight people with type 2 diabetes and 32 individuals with normoglycemia, 30–70 years age, not on medications, underwent blood sampling after overnight (12h) fast and 2 and 4h after a mixed meal (carbohydrates, proteins and fat content 79.1%, 7.7% and 13.2%, respectively). ResultsTriglyceride (TG), TG/HDL-C (high density lipoprotein), HDL-C/LDL-C (low density lipoprotein) ratios, IR parameters, and inflammatory markers were significantly higher among patients with diabetes. There was a fall in total cholesterol (TC), HDL-C and LDL-C at 2 and 4h after the meal in both groups. Compared with fasting, 4-h postprandial TC, TG and HDL-C were significantly better positively correlated with IR in normal individuals. Postprandial hs-CRP was not significantly different to fasting in both groups. Postprandial IL-6 and TNF-α were significantly lower in both groups. ConclusionConsumption of a carbohydrate rich meal is associated with a rise in TG and fall in TC, HDL-C, LDL-C, IL-6 and TNF-α among normal individuals and people with type 2 diabetes.

A CHO/fibre diet reduces and a MUFA diet increases postprandial lipaemia in type 2 diabetes: no supplementary effects of low-volume physical training

The aim of the study was to evaluate the effects of a supervised physical training added to a healthy diet-rich in either carbohydrate and fibre (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia, an independent cardiovascular risk factor particularly relevant in type 2 diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D, of both genders, in good blood glucose control with diet or diet+metformin, with normal fasting plasma lipids. According to a parallel groups 2×2 factorial design, participants were randomized to an 8-week isoenergetic intervention with a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic training programme. The main outcome of the study was the incremental area under the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856). Body weight remained stable during the trial in all groups. Physical fitness slightly improved with training (VO2 peak, 16±4 vs. 15±3ml/kg/min, M±SD, p<0.05). Postprandial triglyceride and cholesterol iAUCs in plasma and chylomicron+VLDL fraction decreased after the CHO/fibre diet, but increased after the MUFA diet with a significant effect for diet by two-way ANOVA (p<0.05). The addition of exercise training to either dietary intervention did not significantly influence postprandial lipid response. A diet rich in carbohydrates and fibre reduced postprandial triglyceride-rich lipoproteins compared with a diet rich in MUFA in patients with T2D. A supervised low-volume physical training did not significantly influence these dietary effects.

The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: Developing a new framework for future therapies

Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by marked elevation of plasma low-density lipoprotein (LDL) cholesterol concentrations and premature coronary artery disease (CHD). In addition to impaired LDL receptor-mediated clearance of LDL particles, in vitro and in vivo studies suggest that hepatic oversecretion of apolipoprotein (apo) B may contribute to the hypercholesterolemia in FH. This may be due to an effect of the expanded hepatic pool of cholesterol (a consequence of increased receptor-independent uptake of LDL) and/or a direct effect of the LDL receptor on apoB secretion. Hepatic oversecretion of apoB may depend on the type and severity of the genetic mutation causing FH. FH can also increase plasma Lp(a) concentration by an undefined mechanism that may not directly involve the LDL receptor pathway. Decreased catabolism of triglyceride-rich lipoproteins could also be due to deficient LDL receptor function, accounting for postprandial dyslipidemia in FH. The metabolism of high-density lipoprotein (HDL) in FH is poorly understood, but preliminary data suggest abnormal HDL composition and functionality, as well as altered transport of apoA-I. Beyond effects related to specific genetic defects in the LDL pathway, co-existing secondary causes, particularly obesity and insulin resistance, and other genetic variants may also perturb lipoprotein metabolism in individuals with FH. Furthermore, residual risk remains high in statin-treated FH. Knowledge of an extended metabolic framework will, therefore, provide the basis for judiciously selecting new pharmacotherapies to treat FH, including apoB antisense oligonucleotides, microsomal transfer protein (MTP) inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

A Comparative Study on the Fasting and the Postprandial Dyslipidaemia in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (Type 2 DM), which is characterized by a relative insulin deficiency or insulin resistance is associated with a cluster of metabolic abnormalities, which includes glucose intolerance, hypertension, a unique dyslipidaemia, a procoagulant state, and an increase in macrovascular diseases. The present study was conducted to assess the significance of postprandial dyslipidaemia with respect to fasting dyslipidaemia, in the pathogenesis of atherosclerotic changes and possible cardiovascular diseases (CVD) and complications. Methods and Statistical Analysis: Fifty diagnosed cases of type 2 DM which were in the age group of 35-65 years, which had a duration of diabetes of more than five years, were included in the study and 50 age and sex matched healthy subjects were taken as the controls. In both the study groups, we measured the serum levels of fasting as well as the postprandial lipid profile, which was comprised of the total Cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and the waist-hip ratio (WHI) as the cardiovascular risk factors. The statistical analysis was done by using the Students unpaired 't'-test. The results of this study showed significantly increased levels of serum total cholesterol, TGs, LDL-C and VLDL-C in the postprandial state as compared to those in the fasting state (p<0.001) and as compared to those in the fasting and the postprandial states of the controls (p<0.001). The serum HDL-C level was significantly lower in the postprandial state as compared to that in the fasting state (p<0.001). Also, the postprandial and the fasting HDL-C levels were significantly lower as compared to the levels in their respective control groups (p<0.001). The findings of the present study indicated that the lipid profile, as a cardiovascular risk factor, was significantly elevated in the postprandial state as compared to that in the fasting state and that it was significantly elevated in the postprandial and the fasting states in the Type 2 DM patients as compared to the levels in their respective control groups. This signified a routine estimation of the postprandial lipid profile, rather than the fasting lipid parameters, in the cardiovascular risk assessment in Type 2 DM.

Regulation of Intestinal Chylomicron Production by Glucagon-Like Peptides

Apolipoprotein B48 (apoB48)-containing triglyceride-rich lipoproteins are atherogenic and therefore it is important to understand factors that regulate their metabolism in the intestine. Insulin resistant states are associated with increased intestinal output of apo B48, but the mechanistic studies explaining this overproduction have relied heavily on models of diet-induced insulin resistance. There is evidence that glucagon-like peptide (GLP) secretion is diminished in insulin resistant and diabetic states, which may have implications for postprandial lipid secretion. This review presents a survey of studies on GLPs and intestinal lipoprotein metabolism, along with some insights into the net physiological significance of GLP action in postprandial lipoprotein metabolism. Studies with GLP-1 receptor agonists and dipeptidyl peptidase-IV inhibitors have indicated that GLP-1 in pharmacological and physiological doses can inhibit intestinal TRL production. On the other hand, GLP-2 has an acute stimulatory effect on intestinal apoB48 secretion. Modulating GLP action may serve as a strategy to improve postprandial dyslipidemia in insulin resistant states.

SOD1 deficiency causes postprandial dyslipidemia due to impaired lipid metabolism in the intestine

SOD1 deficiency causes postprandial dyslipidemia due to impaired lipid metabolism in the intestine

Postprandial Dysmetabolism and the Heart

Epidemiologic evidence indicates that abnormal elevations in glycemia and lipidemia after a meal, termed postprandial dysmetabolism, are linked with increased risk of morbidity and mortality due to cardiovascular disease in individuals with or without type 2 diabetes. Both postprandial hyperglycemia and postprandial hyperlipidemia are independently associated with deteriorating endothelial function and vascular damage, which are likely mediated by increased oxidative stress and are more pronounced when both derangements coexist. Pharmacotherapies that target postprandial hyperglycemia and/or postprandial dyslipidemia are likely to improve endothelial function, which may have positive implications for cardiovascular outcomes.

Postprandial dyslipidaemia and diabetes

There has been a resurgence of interest in the role of triglyceride-rich lipoproteins in the development of atherosclerosis and cardiovascular disease, and this is particularly relevant to diabetes mellitus and the postprandial state. Recent evidence suggests that insulin resistance in diabetes induces postprandial dyslipidemia by increasing the enterocytic production of chylomicrons and their remnant particles, but an impaired clearance capacity is also involved. Postprandial dyslipidaemia in diabetes induces oxidative stress, inflammation and endothelial dysfunction and this may be compounded by dysglycaemia. New guidelines for managing hypertriglyceridaemia in diabetes have been published, first-line therapies being improved glycaemic control, treatment of other secondary causes of dyslipidaemia and statin therapy, followed by judicious use of fibrates, n-3 fatty acids or niacin. A new role for incretin-based therapies in regulating dyslipidaemia has been identified. Postprandial dyslipidaemia is a pivotal mechanism whereby diabetes can induce and accelerate atherosclerosis. Regulating the plasma concentrations of triglyceride-rich lipoproteins may decrease the cardiovascular complications of diabetes. The mechanisms of action of incretin-based treatments on dyslipidaemia and endothelial dysfunction need further investigation. The efficacy of new therapies targeted at postprandial dysmetabolism in diabetes need to be confirmed, against best current levels of care, in clinical endpoint trials.

Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states

In prediabetes and diabetes, hyperglycemia is often accompanied by fasting and postprandial hyperlipidemia. Incretin-based therapies are in increasing clinical use for treating hyperglycemia, but recent evidence emphasizes their ability to improve lipoprotein abnormalities. This is significant as heightened postprandial chylomicron levels during insulin resistance contribute to atherogenic diabetic dyslipidemia. This review summarises the evidence supporting a beneficial effect of incretin-based therapies on diabetic dyslipidemia through modulation of intestinal lipoprotein metabolism. Preclinical and clinical trials have involved administering dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists to healthy and insulin-resistant individuals. Results indicate that enhancing GLP-1R signalling decreases postprandial apoB48-containing triglyceride-rich lipoproteins. These effects may be direct or may be secondary to reduced gastric emptying, increased insulin secretion, or enhanced chylomicron clearance. Enhancing GLP-1R activity improves intestinal lipoprotein metabolism. GLP-1-mediated control of postprandial chylomicron production may be lost in type 2 diabetes in which the incretin response is impaired and in which associated dyslipidemia involves an excess of atherogenic chylomicron remnants. Further human studies are needed to better establish the impact of incretin-based therapies on dyslipidemia, as this offers a major new therapeutic approach to reduce cardiovascular risk in type 2 diabetic patients.

Dietary supplementation of n‐3 PUFA reduces weight gain and improves postprandial lipaemia and the associated inflammatory response in the obese JCR:LA‐cp rat

Postprandial dyslipidaemia occurs in obesity and insulin resistance (IR), and is associated with an increased risk of developing cardiovascular disease. We have recently established that the JCR:LA-cp rodent model develops postprandial dyslipidaemia concomitant with complications of the metabolic syndrome. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) are proposed to modulate plasma lipids, serum hormone levels, lipoprotein metabolism and the inflammatory state; however, results remain inconsistent during conditions of IR. To assess the acute metabolic and inflammatory effects of dietary fish oil supplementation on existing postprandial dyslipidaemia in the JCR:LA-cp model. JCR:LA-cp rats (14 weeks of age) were fed either a control, isocaloric, lipid balanced diet (15% w/w total fat, 1.0% cholesterol, P:S ratio 0.4), a lipid balanced diet with 5% n-3 PUFA [fish oil derived eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] or a lipid balanced diet with 10% n-3 PUFA for 3 weeks. Fasting plasma lipid, cytokine levels, postprandial chylomicron (apoB48) metabolism and the postprandial inflammatory response [haptoglobin and lipopolysaccharide binding protein (LBP)] were assessed following a standardized 'oral fat challenge'. n-3 PUFA treatment resulted in a significant improvement (i.e. decrease) in the postprandial response for triglyceride (45%) (p < 0.05), apoB48 (45%) (p < 0.03) and LBP (33%) (p < 0.05) compared to controls (measured as area under the clearance curve). In contrast, we observed a significant elevation in postprandial haptoglobin (165%) (p < 0.001) in obese rats supplemented with 10% n-3 PUFA. Treatment with 5% n-3 PUFA in the JCR:LA-cp obese animals resulted in a complementary decrease in total body weight gain (6%) (p < 0.001) and an increase (i.e. improvement) in adiponectin (33%) (p < 0.05) compared to controls, without a concomitant reduction in food intake. Acute dietary n-3 PUFA dietary supplementation can improve fasting as well as postprandial lipid metabolism and components of the associated inflammatory response in the JCR:LA-cp rat. Further, moderate dose n-3 PUFA supplementation may reduce corresponding body weight during conditions of hypercholesterolaemia and/or modulate inflammation associated with obesity and the metabolic syndrome.

Type 2 diabetes mellitus is characterized by reduced postprandial adiponectin response: a possible link with diabetic postprandial dyslipidemia

We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (−0.27 ± 0.25 AU, P = .01) but was unchanged in OND ( P = .59) and C ( P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity ( P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism.

Isolation and Characterization of Apolipoprotein B48-Containing Lipoproteins with a Monoclonal Antibody Against Apolipoprotein B48

Remnant lipoproteins are well known to play a pivotal role in atherosclerosis. In patients with postprandial dyslipidemia, metabolic pathways for exogenous lipoproteins are generally disturbed, resulting in accumulation of chylomicron remnants. Although it has been difficult to make a specific antibody against apolipoprotein B48 (apoB48) , a constituent of exogenous lipoproteins, we succeeded in creating a specific monoclonal antibody against apoB48. In this study, we isolated apoB48-containing lipoproteins from lipoproteins with a density less than 1.019 g/mL using this anti-apoB48 monoclonal antibody (4C8). Apolipoproteins and lipids were analyzed to confirm whether apoB48-containing lipoproteins are isolated from other lipoproteins. The characteristics of apoB48-containing lipoproteins in the plasma of patients were compared with type 2 diabetes mellitus and non-diabetic patients. Furthermore, the uptake of apoB48-containing lipoproteins by THP-1 cells (a human acute monocytic leukemia cell line) , HepG2 cells (a human hepatoma cell line) , and human umbilical vein endothelial cells (HUVEC) was investigated. Also, the expression of apoB48 receptors in these cells was tested with RT-PCR. Apolipoprotein analysis of 4C8-bound lipoproteins indicated the isolation of apoB48-containing lipoproteins, because the content of apoB100 was quite low (less than 5%) . Compared with lipoproteins that were not bound to the antibody, apoB48-containing lipoproteins had a higher content of triglycerides. There was no significant difference in the composition of apoB48-containing lipo-proteins between patients with and without type 2 diabetes. Uptake of fluorescence-labeled apoB48-containing lipoproteins by THP-1-derived macrophages and HepG2 cells, but not by HUVEC, was observed. The specificity of this uptake was confirmed because the fluorescent signal was competed out by an excess amount of the same unlabeled lipoproteins. RT-PCR revealed the expression of apoB48 receptors in THP-1 and HepG2 cells but not in HUVEC. These results suggest that specific uptake of apoB48-containing lipoproteins may occur via apoB48 receptors. ApoB48-containing lipoproteins have a higher triglyceride content and are taken up into THP-1-derived macrophages and HepG2 cells by a specific pathway.

Effects of Pitavastatin on Fasting and Postprandial Endothelial Function and Blood Rheology in Patients With Stable Coronary Artery Disease

Because postprandial hypertriglyceridemia and hyperglycemia may promote atherosclerosis, the present study investigated the effects of a clinical dose of pitavastatin on endothelial function and blood rheology in patients with coronary artery disease (CAD) before and after eating a test meal. The 16 patients with stable CAD and mild dyslipidemia and 6 age-matched healthy men as controls were recruited. In each group, forearm blood flow (FBF) was measured during postischemic reactive hyperemia and blood samples were taken before and 2 h after the test meal. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also measured. The patients were started on pitavastatin 2 mg/day. The tests were repeated after 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in CAD patients than in control subjects (P=0.040). Fasting and postprandial FBF during reactive hyperemia significantly improved after pitavastatin treatment (P<0.05 vs baseline data for each phase) associated with reduced urine 8-OHdG, increased plasma adiponectin and improved lipid profile. No significant differences in baseline rheological parameters were seen between controls and CAD patients. Pitavastatin significantly improved fasting and postprandial dyslipidemia and endothelial dysfunction in CAD patients, partly via reducing oxidative stress and increasing plasma adiponectin, although rheological parameters remained unchanged.

Postprandial lipemia, diet, and cardiovascular risk

Recently published studies have provided additional evidence of the pathophysiology and clinical relevance of postprandial dyslipidemia. Notably, the relationship with cardiovascular risk has been considerably strengthened by two large prospective studies showing an independent role for nonfasting plasma triglycerides. Knowledge of the genetic influence has been expanded by the identification of new gene variants associated with postprandial lipemia. More data have confirmed the strict relation between postprandial lipoprotein alterations and insulin resistance, whereas studies on the association with endothelial dysfunction have not been conclusive. Recent medium-term intervention studies have mainly evaluated the different dietary fatty acids and compared diets rich in monounsaturated fatty acids with diets rich in carbohydrates. Results indicate that the diet generally recommended for cardiovascular prevention (ie, low in saturated fat, rich in omega-3 fatty acids, moderately rich in carbohydrates, and rich in fiber) may also correct postprandial lipid abnormalities.

Postprandial dyslipidemia in insulin resistance: Mechanisms and role of intestinal insulin sensitivity

Postprandial dyslipidemia in insulin resistance: Mechanisms and role of intestinal insulin sensitivity

Postprandial dyslipidemia in insulin resistance: Mechanisms and role of intestinal insulin sensitivity

Insulin resistance is strongly associated with metabolic dyslipidemia, which is largely a postprandial phenomenon. Though previously regarded as a consequence of delayed triglyceride-rich lipoprotein clearance, emerging evidence present intestinal overproduction of apoB-48-containing lipoproteins as a major contributor to postprandial dyslipidemia. The majority of mechanistic information is however derived from animal models, namely the fructose-fed Syrian Golden hamster, and extension to human studies to date has been limited. Work in our laboratory has established that aberrant insulin signalling exists in the enterocyte, and that inflammation appears to induce intestinal insulin resistance. The intestine is a major site of lipid synthesis in the body, and upregulated intestinal de novo lipogenesis and cholesterogenesis have been noted in insulin resistant and diabetic states. There is also enhanced dietary lipid absorption attributable to changes in ABCG5/8, NPC1L1, CD36/FAT, and FATP4. Proteins that are involved in chylomicron assembly and secretion, including MTP, MGAT, DGAT, apoAI-V, and Sar1 GTPase, show evidence of increased expression and activity levels. Increased circulating free fatty acids, typically observed in insulin resistant states, may serve to deliver lipid substrates to the intestine for enhanced chylomicron assembly and secretion. To compound the dysregulation of intestinal lipid metabolism, there are changes in the secretion of gut-derived peptides, which include GLP-1, GLP-2, and GIP. Thus, accumulating evidence presents intestinal lipoprotein secretion as a highly regulated process that is sensitive to perturbations in whole body energy homeostasis, and is severely perturbed in insulin resistant states.

Chylomicrons in disease-future challenges: Invited keynote address

It has taken many years to unravel the pathological implications of postprandial dyslipidaemia. Life-style and pharmacological interventions to reduce risk of atherosclerosis have developed empirically, without clear understanding of the underlying mechanisms. Acceptance of the premise that chylomicrons play a key role in atherogenesis brings new understanding to the mechanisms underlying empirical risk-reduction strategies. Raised LDL cholesterol while definitely associated with increased risk, is not present in many patients with established atherosclerosis. A large body of research points to a clear association of atherosclerosis with postprandial dyslipidaemia, not only for coronary disease but also for carotid lesions. Bayesian considerations imply that the majority of the community atherosclerosis burden is attributable to disordered chylomicron metabolism. Risk reduction by life-style interventions such as consumption of low fat meals, Mediterranean diets, low cholesterol intake, weight reduction and exercise can all be explained rationally in terms of the impact of these interventions on chylomicron metabolism. Diabetes is strongly associated with postprandial dyslipidaemia. Needed are long-term controlled trials of life-style interventions and management of dyslipidaemia, with endpoints of progression or regression of atherosclerosis. The paradigm that postprandial dyslipidaemia underlies much of the atherosclerosis burden should become a focus of drug development. Agents that reduce absorption of triglycerides and cholesterol will generally be beneficial. Probucol markedly affects chylomicron metabolism. The mechanism for optimization by Probucol is unclear but appears to be unrelated to effects on oxidation. Adrenergic agonists and thyromimetics are also likely to be beneficial. Statins and fish oils appear beneficial but data are limited. Long-term intervention studies are needed with appropriate attention to improvement in postprandial dyslipidaemia.

Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

Background and aims Postprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue. Methods and results Ten subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) – males, aged 26–59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6 h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/ I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188 ± 28 and 135 ± 22 mg/dl·6 h) than C (87 ± 13 mg/dl·6 h, M ± SEM, p < 0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132 ± 23 vs. 75 ± 14 mg/dl·6 h, p < 0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C. Conclusions In insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity.

Effect of short-term lycopene supplementation and postprandial dyslipidemia on plasma antioxidants and biomarkers of endothelial health in young, healthy individuals

Effect of short-term lycopene supplementation and postprandial dyslipidemia on plasma antioxidants and biomarkers of endothelial health in young, healthy individuals