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In a randomized trial, patients with type 2 diabetes, hypertriglyceridemia, and low HDL cholesterol who received pemafibrate did not have fewer cardiovascular events, although some lipid levels decreased.

Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosity β-glucan consumption in those individuals.

A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR). Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study. We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.

This study was funded by a Wellcome Trust (Biomedical Resource & Multi-User Equipment grant 01506/Z/13/Z) and the British Heart Foundation (Centre of Research Excellence grant RE/18/4/34215). C.T. was supported by a Wellcome Trust Research Training Fellowship (203616/Z/16/Z). The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.

Background/Objectives: The percentage of hypercholesterolemic individuals not reaching their LDL-cholesterol (LDL-C) goal remains high and additional therapeutic strategies should be evaluated. The objective of this study was to evaluate the cholesterol-lowering efficacy and mechanism of action of bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 capsules in hypercholesterolemic adults. Subjects/Methods: A total of 127 subjects completed a randomized, double-blind, placebo-controlled, parallel-arm, multicenter study. Subjects were randomized to consume L. reuteri NCIMB 30242 capsules or placebo capsules over a 9-week intervention period. The primary outcome was LDL-C relative to placebo at the study end point. Results: L. reuteri NCIMB 30242 capsules reduced LDL-C by 11.64% ( P <0.001), total cholesterol by 9.14%, ( P <0.001), non-HDL-cholesterol (non-HDL-C) by 11.30% ( P <0.001) and apoB-100 by 8.41% ( P =0.002) relative to placebo. The ratios of LDL-C/HDL-cholesterol (HDL-C) and apoB-100/apoA-1 were reduced by 13.39% ( P =0.006) and 9.00% ( P =0.026), respectively, relative to placebo. Triglycerides and HDL-C were unchanged. High-sensitivity C-reactive protein and fibrinogen were reduced by 1.05 mg/l ( P =0.005) and 14.25% ( P =0.004) relative to placebo, respectively. Mean plasma deconjugated bile acids were increased by 1.00 nmol/l ( P =0.025) relative to placebo, whereas plasma campesterol, sitosterol and stigmasterol were decreased by 41.5%, 34.2% and 40.7%, respectively. Conclusions: The present results suggest that the deconjugation of intraluminal bile acids results in reduced absorption of non-cholesterol sterols and indicate that L. reuteri NCIMB 30242 capsules may be useful as an adjunctive therapy for treating hypercholesterolemia.

•Type 2 diabetes is associated with dyslipidemia and elevated cardiovascular risk.•Curcuminoids are bioactive polyphenolic natural products.•The impact of curcuminoids on serum lipids in diabetic subjects was investigated.•Curcuminoids supplementation reduced serum non-HDL-cholesterol and Lp(a).•Curcuminoids may reduce cardiovascular risk in diabetic subjects. Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n = 118) were assigned to curcuminoids (1000 mg/day plus piperine 10 mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (−21.86 ± 25.78 versus −17.06 ± 41.51, respectively; p = 0.023), non-HDL-C (−23.42 ± 25.13 versus −16.84 ± 41.42, respectively; p = 0.014) and Lp(a) (−1.50 ± 1.61 versus −0.34 ± 1.73, respectively; p = 0.001) and elevations in serum HDL-C levels (1.56 ± 4.25 versus −0.22 ± 4.62, respectively; p = 0.048) in the curcuminoids group as compared with the placebo group (p < 0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p > 0.05). Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

OBJECTIVE: To evaluate the effect of a culturally sensitive diabetes self-management education program that uses a low-cost, peer-educator format (Project Dulce) on glucose control and metabolic parameters in low-income Mexican Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 207 Mexican-American patients recruited from federally funded community health centers in San Diego County with HbA1c >8% were randomly assigned to the Project Dulce peer intervention or continuation of standard diabetes care. The primary outcome of interest was HbA1c. RESULTS: The majority of subjects were born in Mexico, were female, were middle-aged, had less than an eighth-grade education, and had high baseline HbA1c levels. Significant time-by-group interaction effects for HbA1c (P = 0.02) and diastolic blood pressure (P = 0.04) indicated that the Project Dulce group exhibited greater improvement (i.e., decreases) across time. Within-group analyses showed that the intervention group exhibited significant improvements from baseline to month 4 in absolute levels of HbA1c (–1.7%, P = 0.001) and HDL cholesterol (+1.4 mg/dL, P = 0.01) and from baseline to month 10 in absolute levels of HbA1c (–1.5%, P = 0.01), total cholesterol (–7.2 mg/dL, P = 0.04), HDL cholesterol (+1.6 mg/dL, P = 0.01), and LDL cholesterol (–8.1 mg/dL, P = 0.02). No significant changes were noted in the control group. CONCLUSIONS: This randomized trial, using the Project Dulce model of culturally sensitive, peer-led education, demonstrates improvement in glucose and metabolic control and suggests that this low-cost approach to self-management education for high-risk diabetic populations is effective.

Short-term studies indicate that bempedoic acid, an ATP citrate lyase inhibitor, reduces LDL cholesterol levels. In a 1-year trial, bempedoic acid added to maximally tolerated statin therapy did not lead to a higher incidence of adverse events than placebo and led to significantly lower LDL cholesterol levels.

To evaluate the effects of probiotic (VSL#3) and omega-3 fatty acid on insulin sensitivity, blood lipids, and inflammation, we conducted a clinical trial in 60 overweight (BMI>25), healthy adults, aged 40–60 years. After initial screening the subjects were randomized into four groups with 15 per group. The four groups received, respectively, placebo, omega-3 fatty acid, probiotic VSL#3, or both omega-3 and probiotic, for 6 weeks. Blood and fecal samples were collected at baseline and after 6 weeks. The probiotic (VSL#3) supplemented group had significant reduction in total cholesterol, triglyceride, LDL, and VLDL and had increased HDL (P<0.05) value. VSL#3 improved insulin sensitivity (P<0.01), decreased hsCRP, and favorably affected the composition of gut microbiota. Omega-3 had significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota. Addition of omega-3 fatty acid with VSL#3 had more pronounced effect on HDL, insulin sensitivity and hsCRP. Subjects with low HDL, insulin resistance, and high hsCRP had significantly lower total lactobacilli and bifidobacteria count and higher E. coli and bacteroides count.

In a randomized trial involving patients with high-risk vascular disease, the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers but was not associated with a lower rate of cardiovascular events than placebo. Pharmacologic reduction of the low-density lipoprotein (LDL) cholesterol level with statins substantially decreases the risks of death and complications from cardiovascular causes. 1 , 2 Considerable interest has focused on the identification of approaches that might further reduce cardiovascular-event rates among high-risk patients. 3 Epidemiologic studies have shown inverse associations between high-density lipoprotein (HDL) cholesterol levels and cardiovascular outcomes, 4 – 6 a correlation that persists despite treatment with statins. 7 Nevertheless, therapeutic interventions that raise the HDL cholesterol level have not been shown to reduce cardiovascular risk. Cholesteryl ester transfer protein (CETP) modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins. 8 Two . . .