LDL Particle Size Research Articles

Effects of Small Dense LDL in Diabetic Nephropathy in Females with Type 2 Diabetes Mellitus

Objective: This study investigated the association between small-dense low-density lipoprotein (sdLDL) and diabetic nephropathy (DN) in type 2 diabetic patients. Methods: A total of 172 type 2 diabetic patients (95 men and 77 women) who had not taken lipid-lowering agents were enrolled in this study. Measured LDL cholesterol fractionates into seven parts (LDL1 through 7) according to the size and the extent of charge. Using this system, we analyzed mean LDL particle size and the proportion of sdLDL (the percent of LDL3 through 7 over whole LDL). DN was defined as the albumin-to-creatinine ratio (ACR) ≥30 mg/g after excluding other causes of proteinuria. Results: The mean LDL cholesterol, LDL cholesterol size, proportion of sdLDL and ACR did not differ significantly between males and females. The presence of DN was negatively correlated with mean LDL size (r=-0.33, p value=0.02) and positively correlated with the proportion of sdLDL (r=0.34, p value=0.01) in females but not in males. After adjusting for other confounding factors related to DN, mean LDL size and proportion of sdLDL remained independent risk factors for DN in females [for mean LDL size, Odds ratio (OR)=0.86, 95% Confidence interval (CI)=0.77-0.96, p=0.01; for proportion of sdLDL, OR=1.07, 95% CI: 1.10-1.12, p=0.01], but not in males. Conclusion: sdLDL is closely related to DN in female type 2 diabetic patients. Further studies are necessary to clarify the association of sdLDL and DN with gender. (J Lipid Atheroscler 2016 June;5(1):11-19)

Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk. To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients. VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30mg/d, 100mg/d, or 500mg/d) or in combination with statins (100mg plus simvastatin 40mg/d, atorvastatin 20mg/d, or rosuvastatin 10mg/d; Clinicaltrials.gov Identifier: NCT01105975). Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000nmol/L) and sLDL (>600nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size. Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD.

Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role. The objective of the study was to determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD. This was a cross-sectional study. The study was conducted at a university hospital. Patients were recruited from outpatient clinics or from the general population (n = 188). Measurement of hepatic triglyceride content by magnetic resonance spectroscopy, histology (liver biopsy), metabolic profile by means of an oral glucose tolerance test, and lipoprotein analyses were performed. Outcomes measured included standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, low-density lipoprotein (LDL) particle size/phenotype, and LDL/high-density lipoprotein subfractions), and insulin resistance. Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared with patients without NAFLD. Despite small differences in triglycerides and high-density lipoprotein-cholesterol, patients with NAFLD had a significantly higher plasma apolipoprotein B to apolipoprotein A1 ratio (0.66 ± 0.02 vs 0.58 ± 0.02, P = .01) and smaller LDL particle size (216.2 ± 0.7 vs 219.4 ± 1.1 Å, P = .01). Of note, these differences between patients with/without NAFLD were independent of the presence of obesity. Severity of steatohepatitis did not significantly influence the lipoprotein profile. Worse atherogenic dyslipidemia was best predicted by the degree of liver fat accumulation and adipose tissue and systemic insulin resistance. NAFLD was associated with a worse atherogenic lipoprotein profile, regardless of similar body mass index and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease (nonalcoholic steatohepatitis).

Structural analysis of APOB variants, p.(Arg3527Gln), p.(Arg1164Thr) and p.(Gln4494del), causing Familial Hypercholesterolaemia provides novel insights into variant pathogenicity.

Familial hypercholesterolaemia (FH) is an inherited autosomal dominant disorder resulting from defects in the low-density lipoprotein receptor (LDLR), in the apolipoprotein B (APOB) or in the proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the majority of the cases FH is caused by mutations occurring within LDLR, while only few mutations in APOB and PCSK9 have been proved to cause disease. p.(Arg3527Gln) was the first mutation in APOB being identified and characterized. Recently two novel pathogenic APOB variants have been described: p.(Arg1164Thr) and p.(Gln4494del) showing impaired LDLR binding capacity, and diminished LDL uptake. The objective of this work was to analyse the structure of p.(Arg1164Thr) and p.(Gln4494del) variants to gain insight into their pathogenicity. Secondary structure of the human ApoB100 has been investigated by infrared spectroscopy (IR) and LDL particle size both by dynamic light scattering (DLS) and electron microscopy. The results show differences in secondary structure and/or in particle size of p.(Arg1164Thr) and p.(Gln4494del) variants compared with wild type. We conclude that these changes underlie the defective binding and uptake of p.(Arg1164Thr) and p.(Gln4494del) variants. Our study reveals that structural studies on pathogenic variants of APOB may provide very useful information to understand their role in FH disease.

Predictive associations between serum fatty acids and lipoproteins in healthy non-obese Norwegians: implications for cardiovascular health.

A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patterns. Predictive FA patterns were revealed for lipoprotein features of importance for cardiovascular (CV) health. Thus, the subclasses of atherogenic small and very small low density lipoprotein (LDL) particles and the same subclasses of high density lipoprotein (HDL) particles were associated with a pattern of saturated FAs and mono-unsaturated C16-C18 FAs. Eicosapentaenoic acid (EPA) and the ratio of EPA to arachidonic acid (AA) had strongest associations to features that promotes CV health: (i) large average size of HDL and LDL particles, and, (ii) small average size of very low density lipoprotein (VLDL) particles. Total concentration of HDL in both genders correlated to EPA, but docosahexaenoic acid (DHA) correlated just as strongly for women. For men, docosapentaenoic acid (DPA) showed stronger association to HDL concentration than EPA. For both genders, concentration of large LDL particles showed associations to levels of EPA, but stronger to DHA and DPA. High values of EPA/AA seem to be the strongest single biomarker for good CV health in both men and women.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-015-0886-4) contains supplementary material, which is available to authorized users.

Effect of consuming novel foods consisting high oleic canola oil, barley β-glucan, and DHA on cardiovascular disease risk in humans: the CONFIDENCE (Canola Oil and Fibre with DHA Enhanced) study – protocol for a randomized controlled trial

BackgroundMetabolic syndrome (MetS) has been identified as a major contributor to the development of cardiovascular disease (CVD). Current recommendations for dietary management of people with MetS involve quantitative and qualitative modifications of food intake, such as high consumption of vegetables, fruits, and whole grain foods. The results from our previous human trials revealed the potential of the dietary components high-oleic acid canola oil (HOCO)-docosahexaenoic acid (DHA) and high molecular weight barley β-glucan individually in managing CVD risk factors. Foods with a combination of HOCO-DHA and barley β-glucan have never been tested for their effects on CVD risk. The objective is to determine the effects of consuming novel foods HOCO-DHA, and barley β-glucan on managing CVD risk factors in people with MetS.Methods/DesignWe are conducting a randomized, single-blind crossover trial with four treatment phases of 28 days each separated by a 4-week washout interval. Participants (n=35) will be provided with weight-maintaining, healthy balanced diet recommendations according to their energy requirements during the intervention periods. Participants will receive muffins and cookies as treatment foods in a random order and will consume at least one meal per day at the research center under supervision. The four treatments include muffins and cookies consisting of (1) all-purpose flour and HOCO-DHA (50 g/day); (2) barley flour (4.36 g/day of β-glucan) and a blend of sunflower oil, safflower oil, and butter as control oil (50 g/day); (3) barley flour (4.36 g/day of β-glucan) and HOCO-DHA (50 g/day; dosage of DHA would be 3 g/day); and (4) all-purpose flour and control oil (50 g/day). At the beginning and end of each phase, we will evaluate anthropometrics; systolic and diastolic blood pressure; blood lipid profile; low-density lipoprotein subfractions and particle size; 10-year Framingham CVD risk score; inflammatory status; and plasma and red blood cell fatty acid profiles, fecal microbiome, and body composition by dual-energy X-ray absorptiometry.ConclusionCholesterol synthesis will also be studied, using a stable isotope approach. The proposed study will lead to innovation of novel food products, which may result in improvement in the overall cardiovascular health of humans.Trial registrationClinical trials.gov identifier: NCT02091583. Date of registration: 12 March 2014.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduced body adiposity and Lp-PLA2 activity in overweight subjects

The effect of consumption of two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, on weight loss, body adiposity and lipoprotein-associated phospholipase A2 (Lp-PLA2) activities in overweight subjects was examined. After 12-week probiotic treatment, the probiotic group presented reductions in body weight (−0.65 ± 0.23 kg), body fat percentage (−0.57 ± 0.19%) and body fat mass (−616 ± 161 g) measured using DEXA, and L1 subcutaneous fat area (−2.68 ± 1.31 cm2) measured using CT, compared to baseline. The probiotic group exhibited greater reductions in oxidized low density lipoprotein (ox-LDL) (P < 0.001) and Lp-PLA2 (P < 0.001) and a greater increase in low density lipoprotein (LDL) particle size (P = 0.001) than the placebo. The change (△, difference from baseline) in total fat mass correlated with △ Lp-PLA2 (r = 0.480, P < 0.001), which correlated with △ ox-LDL (r = 0.537, P < 0.001). Probiotic-induced weight loss was associated with reductions in fat mass, which correlated with the changes in Lp-PLA2 activities (ClinicalTrials.gov: NCT02492698).

Estimation of LDL Particle Size Using Lipid Indices: A Population-Based Study of 1578 Schoolchildren.

Low-density lipoprotein (LDL) is atherogenic and LDL particles are reduced in diameter in the presence of insulin resistance, forming small, dense LDL. This study was conducted to assess the relationship between commonly used lipid indices and LDL particle size and furthermore to clarify the best surrogate lipid markers that could conveniently be used to estimate LDL particle size in children. We determined LDL particle diameter by gradient gel electrophoresis in 1578 children aged 10-12 years. At the fasting state, the relationships between measured LDL particle size and lipid variables [total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), atherogenic index [(TC-HDL-C)/HDL-C, TG/HDL-C, LDL-C/HDL-C, and LDL-C/apolipoprotein B (Apo B) and non-HDL-C (TC-HDL-C)] were analyzed. The LDL particle diameter was 26.64 (mean) ± 0.48 (SD) nm in boys (n = 820) and 26.66 ± 0.49 nm in girls (n = 758); there was not a statistically significant difference. There were statistically significant correlations between LDL particle size and TG or HDL-C concentrations (r = 0.28∼0.37), but the correlations with LDL-C and ApoB were very weak. The combined lipid measures, such as atherogenic index, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C showed moderate correlations (r = 0.33∼0.38) with LDL particle size; however, the correlation of non-HDL-C with LDL particle size was weak (r = 0.18∼0.19). Simple HDL-C measure appeared to be of comparable value to combined lipid measures. Our data indicate that various lipid indices are not superior to HDL-C levels alone as a clinical tool for estimating LDL particle size. Non-HDL-C was less valuable in this aspect.

Phytosterols, Phytostanols, and Lipoprotein Metabolism

The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be diminished.

Circulating non–HDL-C levels were more relevant to atherogenic lipoprotein subfractions compared with LDL-C in patients with stable coronary artery disease

Conflicting results have been yielded as to whether low-density lipoprotein (LDL) cholesterol (LDL-C) or non-high-density lipoprotein (HDL) cholesterol (non-HDL-C) is a better marker of coronary artery disease (CAD) risk. Recently, plasma LDL and HDL subfractions have been suggested to be more accurately reflecting the lipoproteins' atherogenicity. We sought to compare the relationship between LDL-C or non-HDL-C and lipoprotein subfractions. We conducted a cross-sectional study in 351 consecutive stable CAD patients without lipid-lowering therapy. The LDL and HDL separations were performed using the Lipoprint System. The LDL-C levels were measured directly, and the non-HDL-C levels were calculated. The cholesterol concentrations of LDL (large, medium, and small) and HDL (small) particles were increased (all P<.001) by non-HDL-C or LDL-C quartiles, whereas the mean LDL particle size and cholesterol concentrations of HDL (large) were decreased (both P<.001) by non-HDL-C quartiles. In age- and gender-adjusted analysis, the cholesterol in small LDL was much strongly related to non-HDL-C than to LDL-C (r=0.539 vs 0.397, both P<.001). Meanwhile, the mean LDL particle size was more closely associated with non-HDL-C than LDL-C (r=-0.336 vs r=-0.136, both P<.05). Significantly, the cholesterol in large HDL was negatively correlated with non-HDL-C (r=-0223, P<.001) but not with LDL-C. These correlations were further confirmed by the fully adjusted multivariable linear regression analysis. Non-HDL-C, in comparison to LDL-C, was more relevant to atherogenic lipoprotein subfractions in patients with stable CAD, supporting that it may be better in assessing cardiovascular risk.

Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein-Related Measures.

Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥ 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia

Previous studies have indicated that supplementation with probiotics might improve lipid metabolism. The objective of the study was to evaluate the effect of supplementation with probiotic strains Lactobacillus curvatus (L.curvatus) HY7601 and Lactobacillus plantarum (L.plantarum) KY1032 on triglyceride (TG) and apolipoprotein A-V (apo A-V) levels. A randomized, double-blinded, placebo-controlled study was conducted with 128 non-diabetic subjects with hypertriglyceridemia. Over a 12-week test period, the probiotic group consumed 2g/day of a powdered supplement containing L.curvatus HY7601 and L.plantarum KY1032, whereas the placebo group consumed a powder lacking probiotics. After the treatment, the probiotic group showed an 18.3% (P<0.001) reduction in TGs and increases of 21.1% (P=0.001) and 15.6% (P<0.001) in the apo A-V and LDL particle size, respectively. The probiotic group had a significant reduction in TGs (P=0.040) and increases in the plasma apo A-V (P=0.003) and LDL particle size (P<0.001) compared with the placebo group. In the probiotic group, the reduction in the TG levels was negatively correlated with changes in the apo A-V and baseline TGs, regardless of the APOA5 -1131T>C genotype. The consumption of two probiotic strains for 12 weeks reduced TGs and increased the apo A-V and LDL particle size in hypertriglyceridemic subjects. This effect was more pronounced in subjects with higher levels of fasting TGs regardless of their APOA5 -1131T>C genotype.

The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review

Cholesterol plays a vital role in cell biology. Dietary cholesterol or “exogenous” cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith–Lemli–Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

Associations between metabolomic‐identified changes of biomarkers and arterial stiffness in subjects progressing to impaired fasting glucose

We investigated correlations between age-related changes in circulating metabolites and arterial stiffness in impaired fasting glucose (IFG). This prospective cohort study included 602 healthy, normal fasting glucose (NFG) subjects (30-65years old) who underwent triennial medical evaluation. After 3years, 9·3% of subjects developed IFG (n=56). Age, gender, BMI and fasting glucose were used to match the remaining NFG subjects (n=546) that were included for the control group (NFG group, n=80). After 3years, levels of fasting glucose, insulin and malondialdehyde, and brachial-ankle pulse wave velocity (baPWV) were significantly greater in the IFG group than in the NFG group after adjusting for baseline values. The IFG group had a greater increase in lactosylceramide (P=0·001, q<0·05) and a greater reduction in phosphatidylcholine (PC) (18:0/20:4) than the NFG group. Multiple linear regression analysis showed that the change in baPWV was independently and positively associated with changes in fasting glucose and lactosylceramide. In all subjects, lactosylceramide levels positively correlated with changes in baPWV and fasting glucose, while premenopausal women were not shown, and negatively correlated with changes in PC and LDL particle size. This study indicates that age-related increase in circulating lactosylceramide is an independent predictor of increased arterial stiffness in subjects with impaired fasting glucose.

Analysis of Lipoprotein Subfractions in Chinese Han Patients with Stable Coronary Artery Disease

The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study

The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors. This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg, n=14) or glimepiride (0.5 mg, n=16). In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (-8.5% and -9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (-8.6% and -7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (-13.9% vs. -8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (-6.9% vs. -3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups. There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial

Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23g of inositols in 250ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24h after consumption of the IEB. Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation

Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet). The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24–53 years) with slightly elevated LDL-C concentrations (3.4–4.9 mmol/L) or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255–260 Å) (p for sex-by-time interaction = 0.01) and small, dense LDL (sdLDL; <255 Å) (trend; p for sex-by-time interaction = 0.06), men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference. Results suggest that short-termconsumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet.

Abstract 273: HDL Particle Concentration Inversely Associates with Incident Metabolic Syndrome in the Multiethnic Dallas Heart Study

Objective: Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and other recognized risk factors. Methods: HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30-65. Participants with prevalent MetS, DM, CVD, cirrhosis, cancer, HIV, or renal failure were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 9.4 years. Results: Among a cohort of 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r=0.54, p&lt;0.0001). The lowest quartile of HDL-P was associated with younger age, men, Hispanic ethnicity, lower total, HDL, and LDL cholesterol levels and particle sizes, and less reported alcohol intake. Participants in the lowest sex and race stratified quartile of HDL-P had the highest incidence of MetS (Figure). In models adjusted for traditional risk factors, HDL-C, visceral fat, HOMA-IR, and hs-CRP, the lowest quartile of HDL-P was associated with 65% increased risk of incident MetS (Figure). Conclusion: HDL-P is independently associated with incident MetS after adjustment for HDL-C, adiposity, inflammation, and markers of insulin sensitivity. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association.

Relationship between plasma phospholipase A2 concentrations and lipoprotein subfractions in patients with stable coronary artery disease

BackgroundBoth increased lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and atherogenic lipoprotein subfractions have been shown to reflect unfavourable cardiovascular risk. However, the correlation between Lp-PLA2 and lipoprotein subfractions in patients with coronary artery disease (CAD) has not been assessed yet. MethodsA total of 324 consecutive subjects who were not treated with lipid-lowering drugs were enrolled (angiographically proven CAD: n=253; non-CAD: n=71). Plasma Lp-PLA2 concentrations were measured using ELISA. The low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were determined by Lipoprint System. ResultsPlasma Lp-PLA2 concentrations were higher in patients with CAD compared with those without CAD (153.61±78.73 vs. 131.41±65.49ng/ml, p=0.028). The univariable correlation analysis revealed that Lp-PLA2 concentrations were positively correlated with the cholesterol concentrations of each LDL subfractions and the intermediate as well as small HDL subfractions, while negatively linked with the LDL particle size and large HDL-cholesterol (HDL-C) concentrations in CAD group. However, no similar results were observed in the non-CAD group. Furthermore, multivariable regression analysis was performed in patients with CAD and showed that plasma Lp-PLA2 concentrations were independently correlated with the cholesterol concentrations of each LDL subfractions [large LDL-cholesterol (LDL-C): β=0.263, p<0.001; intermediate LDL-C: β=0.327, p<0.001; small LDL-C: β=0.135, p=0.033] and small HDL-C (β=0.133, p=0.034). ConclusionLp-PLA2 concentrations were positively associated with all LDL subfractions and small HDL subfraction, suggesting an interaction between Lp-PLA2 and lipoprotein subfraction phenotypes in the status of CAD.