Lipoprotein Triglyceride Concentrations Research Articles

A CASE STUDY- MANAGEMENT OF DYSLIPIDEMIA W.S.R. TO MEDO DHATU DUSTI THROUGH AYURVEDA MANAGEMENT

Dyslipidemia is a disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency. These disorders may be manifested by an elevation of the serum total cholesterol, low-density lipoprotein (LDL) cho-lesterol and triglyceride concentrations and a decrease in the high-density lipoprotein (HDL) cholesterol concen-tration. As per Ayurveda, Acharya Charaka has counted Sthoulya under the eight impediments designated as Ninditapurusha. Lipids are discussed in terms of Sneha Dravya in Ayurveda. Mansa Dhatu is combined with Agni-Medodhatwagni, stirred up by the Agni, combined with the quality of Apa and unctuous substance, and finally converted into Medodhatu. As Chikitsa sutra of Medo Vridhi, Lekhan Karma is an essential therapeutic measure. Moreover, drugs of Arogya Vardhini Vati, Avipattikar Churna, Navaka Guggulu, Yakrit plihari Loha and Lekhaniya Mahakashaya are most effective in the management of Medo Dhatu Dushti or Medo Vridhi. INTRODUCTION: AIM AND OBJECTIVES- To evaluate the role of Ayurvedic Formulations in managing Medovriddhi with particular reference to Dyslipidemia. MATERIAL AND METHODS – A 44-year-old male patient came with the complaint of nausea, vomiting and burning sensation in the chest region and feet for the last two months. The patient has taken 20 days of modern medicine, but no relief was found, so he came to Ayurveda Hospital for better treatment. RESULT AND DIS-CUSSION The outcomes were noteworthy regarding the clinical and analytical criteria. According to statistics, there is an improvement in nausea, vomiting, and burning sensation in the chest region and feet, as well as cho-lesterol, triglycerides, LDL, and VLDL levels.

Effects of Physical Activity on Blood Lipids and Hemoglobin A1c in Healthy Pregnant Women: The FitMum Randomized Controlled Trial

ObjectiveMaternal blood lipid and glucose concentrations during pregnancy affect fetal growth and the risk of pregnancy and delivery complications.We aimed to investigate the effects of physical activity (PA) during pregnancy on maternal blood lipid and hemoglobin A1c (HbA1c) concentrations. We hypothesized that higher PA was associated with improved lipid profile and glycemic control. MethodsIn a secondary analysis of a randomized controlled trial, we included 216 pregnant women before week 15 + 0 and tested the effects of two different PA interventions throughout pregnancy compared to standard care on maternal blood lipid and HbA1c concentrations. Additionally, we investigated the effect of PA per se measured by an activity tracker. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, and HbA1c concentrations were measured at week ≤15 + 0, 28+0-6, 34+0-6, and at delivery (week 32 + 1 to 42 + 0). Effects of the interventions and PA per se were tested using linear mixed effects models and linear regression analyses, respectively. ResultsNo effects of the PA interventions were detected on maternal lipids or HbA1c during pregnancy. In PA per se analyses, more minutes per week of moderate-to-vigorous intensity PA were associated with less increase in TC (−1.3E-04, P = .020) and LDL-C (−8.5E-05, P = .035) as pregnancy progresses. More active kilocalories were associated with less increase in TC (−5.5E-05, P < .001), HDL-C (−9.5E-06, P = .024), and LDL-C (−3.2E-05, P = .005). ConclusionWhilst there were no effects of offering PA interventions, higher PA was associated with reduced increases in TC, HDL-C, and LDL-C as pregnancy progressed.

Women with gestational diabetes mellitus, controlled for plasma glucose level, exhibit maternal and fetal dyslipidaemia that may warrant treatment

AimsTo compare maternal and fetal cord plasma and lipoprotein triglyceride (TG) concentrations in women with Gestational Diabetes Mellitus (GDM), with hyperglycaemia and hypertriglyceridaemia, and healthy women. MethodsFasted maternal blood at 28.6 ± 3.4 (T1) and 36.2 ± 1.0 (T2) [mean ± S.D] weeks of gestation, and cord blood were collected. Plasma lipoprotein fractions underwent compositional analysis. ResultsPlasma glucose did not differ between GDM and healthy women. T1 maternal plasma TG (2.60 ± 0.89 mmol/l versus 1.71 ± 0.69 mmol/l) and plasma apolipoprotein B (1.30 ± 0.48 g/l versus 0.75 ± 0.40 g/l) were higher in GDM compared to healthy. Maternal plasma TG increased over gestation in both groups. T1 plasma VLDL total protein (38 ± 15 mg/dl versus 25 ± 11 mg/dl), total cholesterol (TC) (30 ± 14 mg/dl versus 16 ± 13 mg/dl) and phospholipid (PL) (43 ± 17 mg/dl versus 26 ± 16 mg/dl) were higher in GDM than healthy, and similarly for IDL, suggesting increased lipoprotein particle number. T1 VLDL-TG enrichment was higher in healthy and increased over gestation in GDM women but decreased in healthy. IDL-TG enrichment (TG/TC) increased over gestation in women with GDM and decreased in healthy. Cord blood VLDL, IDL and LDL from GDM had a two-fold higher TG enrichment than healthy pregnancy. ConclusionIncreased maternal lipoprotein number, but not TG enrichment, in GDM mothers may explain TG enrichment of cord lipoproteins.

(297) Evaluation of Endothelial Function and Metabolic Profile in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy

Abstract Introduction Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c &amp;gt;9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg. Results A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution. Conclusions Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No

Short-term Intensive Lifestyle Therapy in a Worksite Setting Improves Cardiometabolic Health in People With Obesity.

The Pritikin Program, which provides intensive lifestyle therapy, has been shown to improve cardiometabolic outcomes when provided as a residential program. The purpose of the present study was to conduct a short-term, randomized, controlled trial to evaluate the feasibility and clinical efficacy of treatment with the Pritikin Program in an outpatient worksite setting. Cardiometabolic outcomes were evaluated in people with overweight/obesity and ≥2 metabolic abnormalities (high triglycerides, low high-density lipoprotein (HDL) cholesterol, high blood pressure, HbA1c > 5.7%), before and after they were randomized to 6 weeks of standard care (n = 26) or intensive lifestyle therapy, based on the Pritikin Program (n = 28). Participants in the lifestyle intervention group were provided all food as packed-out meals and participated in group nutrition, behavioral education, cooking classes, and exercise sessions 3 times per week at a worksite location. Compared with standard care, intensive lifestyle therapy decreased body weight (-5.0% vs -0.5%), HbA1c (-15.5% vs +2.3%), plasma total cholesterol (-9.8% vs +7.7%), low-density lipoprotein cholesterol (-10.3% vs +9.3%) and triglyceride (-21.7% vs +3.0%) concentrations, and systolic blood pressure (-7.0% vs 0%) (all P values < .02), and increased exercise tolerance (time to exhaustion walking on a treadmill by +23.7% vs +4.5%; P < .001). This study demonstrates the feasibility and clinical effectiveness of short-term, intensive outpatient lifestyle therapy in people with overweight/obesity and increased risk of coronary heart disease when all food is provided and the intervention is conducted at a convenient worksite setting.

Assessment of Lipid Parameters and Oxidative Stress Markers in Wistar Rats Treated with Extracts of Rhizophora mangle

Medicinal plants are considered more accessible, affordable and also associated with minimal side effects compared to orthodox medicines in most developing countries. These factors in addition to multiple cultural and long term historical relevance have contributed to its increasing popularity around the world. This study was carried out to assess the antioxidative and serum lipid effects of leaf extract of Rhizophora mangle on male Wistar rats. Male Wistar rats were divided into four (4) groups of five (5) rats each. Group one (1) served as control and received distilled water. Group two (2) and group three (3) were treated with 200mg/kg bw and 400mg/kg bw of the ethanolic extract of Rhizophora mangle respectively. Group four (4) was treated with 600mg/kg of the extract. Extract administration lasted for 30 days. The results obtained showed that the extract did not cause significant changes in superoxide dismutase, catalase, gluthathione reductase enzyme activities but decreased gluthathione peroxidase enzyme activity. The level of malondialdehyde was not altered. The lipid parameters including low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride and total cholesterol concentrations were not significantly affected. This study showed that, extracts of Rhizophora mangle did not alter the level of lipid peroxidation and may not confer any benefits against development of lipid induced-cardiovascular disorders.

Effect of dyslipidemia, obesity, and atopic status on exhaled and alveolar nitric oxide in asthmatic children.

Dyslipidemia and obesity contribute to a pro-inflammatory state. Eosinophilic airway inflammation can be indirectly measured by fractional exhaled nitric oxide (FeNO) produced in the airways of asthmatic subjects. To compare exhaled nitric oxide (NO) and alveolar NO in asthmatic children with and without dyslipidemia. Asthmatic children (5-18 years old) had fasting serum low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) concentrations measured. FeNO was measured at constant flow rates of 20, 50, 100, and 300 ml/s by the chemiluminescence method. NO concentrations in tissue of the upper airways (CawNO) and the total flux of NO in the conducting airways (JawNO) were determined through FeNO at 20, 100, and 300 ml/s using a mathematical model. The atopic status was assessed using the skin prick test for aero-allergens. One hundred forty-one asthmatic children were enrolled with a mean (standard deviation) age of 11.82 (3.38) years. Sixty-four (45.4%) children had dyslipidemia and 20 (14.2%) were obese. Children with low HDL-C concentrations had significantly higher CawNO and JawNO than those with normal HDL-C concentrations (both p = 0.03). Asthmatic children with obesity had higher CRP concentrations than those with a normal weight (p < 0.001). Atopic children had a significantly higher FeNO, CawNO, and JawNO than non-atopic children (all p < 0.05). This study suggests an effect of HDL-C on CawNO and JawNO in asthmatic children. An intervention that normalizes HDL-C concentrations may be beneficial for airway inflammation in asthmatic children.

Effects of USF1 SNPs and SNP-Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population.

BackgroundUpstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China.MethodsSix USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD.ResultsThe genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C–rs2774276G–rs2516839A and rs3737787C–rs2774276G–rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C–rs2774276G–rs2516839A and rs3737787T–rs2774276C–rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05–0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (pI < 0.001). The expression levels of the USF1 mRNA, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1β, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1β, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01).ConclusionSex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1β, TNF-α, and IL-6.

Mendelian randomization study of circulating lipids and biliary tract cancer among East Asians

BackgroundAssociations of High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (CHL), and triglyceride (TRG) concentrations with risk of biliary tract cancer (BtC) were conflicting in observational studies. We aim to investigate the causal link between circulating lipids and BtC using genetic information.MethodsSingle nucleotide polymorphisms of the four circulating lipids (n = 34,421) and BtC (418 cases and 159,201 controls) were retrieved from two independent GWAS studies performed in East Asian populations. Two-sample univariate and multivariate Mendelian Randomization (MR) analyses were conducted to determine the causal link between circulating lipids and BtC.ResultsNo significant horizontal pleiotropy was detected for all circulating lipids according to the MR-PRESSO global test (P = 0.458, 0.368, 0.522, and 0.587 for HDL, LDL, CHL, and TRG, respectively). No significant evidence of heterogeneity and directional pleiotropy was detected by the Cochran’s Q test and MR-Egger regression. Univariate MR estimates from inverse variance weighting method suggested that one standard deviation (1-SD) increase of inverse-normal transformed HDL (OR = 1.38, 95% CI 0.98–1.94), LDL (OR = 1.46, 95% CI 0.96–2.23), and CHL (OR = 1.34, 95% CI 0.83–2.16) were not significantly associated with BtC risk. Whereas 1-SD increase of inverse-normal transformed TRG showed a significantly negative association with BtC risk (OR = 0.48, 95% CI 0.31–0.74). In multivariate MR analyses including all the four lipid traits, we found that 1-SD increase of LDL and TRG was significantly associated with elevated (OR = 1.32, 95% CI 1.04–2.01) and decreased (OR = 0.54, 95% CI 0.42–0.68) risk of BtC, respectively.ConclusionCirculating lipids, particularly LDL and TRG, may have roles in the development of BtC. However, the results of this study should be replicated in MR with larger GWAS sample sizes for BtC.

Association of Dyslipidemia and Respiratory Resistance Assessed by the Forced Oscillation Technique in Asthmatic Children.

This study aimed to evaluate the associations between dyslipidemia and pulmonary function parameters assessed by spirometry and the forced oscillation technique in asthmatic children. Asthmatic children (5-18years old) had fasting serum lipid profiles including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) measured. Pulmonary function tests were assessed by spirometry and the forced oscillation technique (FOT). One hundred forty-one asthmatic children were enrolled with a mean (SD) age of 11.82 (3.38) years. Eighty-eight (62.4%) children were boys, 64 (45.4%) had dyslipidemia, and 20 (14.2%) were obese. Among the children with dyslipidemia, a high LDL-C concentration (65.6%) was the most common form of dyslipidemia, followed by high TC (57.8%), high TG (35.9%), and low HDL-C concentrations (15.6%). Multivariable analysis showed significant associations between HDL-C concentrations and respiratory resistance at 5Hz (R5) and respiratory resistance at 20Hz (R20), and TC concentrations were modestly associated with reactance at 5Hz (X5), the frequency of resonance (Fres), and the area of reactance (ALX). Asthmatic children who had high LDL-C concentrations had a significantly higher expiratory phase R5, whole breath R20, and expiratory phase R20 than those in children with normal LDL-C concentrations. This study suggests an association of blood cholesterol, especially HDL-C and LDL-C, and respiratory resistance measured by the FOT, irrespective of the obesity status. An intervention for improving LDL-C and HDL-C concentrations may be beneficial on lung function parameters in asthmatic children. TCTR20200305005; date of registration: 03-04-2020 (retrospectively registered).

Impact of PCSK9 Immunization on Glycemic Indices in Diabetic Rats.

Methods To prepare the anti-PCSK9 vaccine, a peptide construct called Immunogenic Fused PCSK9-Tetanus (IFPT) was linked to the surface of nanoliposome carriers. Healthy rats received four subcutaneous injections of the vaccine at biweekly intervals. Two weeks after the last vaccination, anti-PCSK9 antibody titers, PCSK9 targeting, and inhibition of PCSK9–low-density lipoprotein receptor (LDLR) interaction were evaluated. After verification of antibody generation, the immunized rats were intraperitoneally treated with a single dose (45 mg/kg) of streptozotocin (STZ) to induce diabetes mellitus. The levels of fasting blood glucose (FBG) were measured, and the oral glucose tolerance test (OGTT) as well as the insulin tolerance test (ITT) were carried out to assess glycemic status. At the end of the study, the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol concentrations were assayed. Histopathology examination of the liver and pancreas was also performed using the hematoxylin-eosin staining method. Results The prepared nanoliposomal vaccine could strongly induce anti-PCSK9 antibodies in the vaccinated rats. Within one week following the STZ injection, the FBG level was lower in the vaccinated group vs. diabetic control group (49% (−171.7 ± 35 mg/dL, p < 0.001)). In the OGTT, the injected rats showed improved glucose tolerance as reflected by the reduction of blood glucose levels over 180 min, compared with the diabetic controls. Moreover, the ITT demonstrated that, after the insulin injection, blood glucose concentration declined by 49.3% in the vaccinated group vs. diabetic control group. Expectedly, the vaccinated rats exhibited lower (-26.65%, p = 0.03) plasma LDL-C levels compared with the diabetic controls. Histopathology examination of pancreas tissue demonstrated that the pancreatic islets of the vaccinated rats had a slight decline in the population of β-cells and few α-cells. Normal liver histology was also observed in the vaccinated rats. Conclusion PCSK9 inhibition through the liposomal IFPT vaccine can improve the glucose and insulin tolerance impairments as well as the lipid profile in diabetes.

Identification of EP300 as a Key Gene Involved in Antipsychotic-Induced Metabolic Dysregulation Based on Integrative Bioinformatics Analysis of Multi-Tissue Gene Expression Data.

Antipsychotics (APs) are associated with weight gain and other metabolic abnormalities such as hyperglycemia, dyslipidemia and metabolic syndrome. This translational study aimed to uncover the underlying molecular mechanisms and identify the key genes involved in AP-induced metabolic effects. An integrative gene expression analysis was performed in four different mouse tissues (striatum, liver, pancreas and adipose) after risperidone or olanzapine treatment. The analytical approach combined the identification of the gene co-expression modules related to AP treatment, gene set enrichment analysis and protein-protein interaction network construction. We found several co-expression modules of genes involved in glucose and lipid homeostasis, hormone regulation and other processes related to metabolic impairment. Among these genes, EP300, which encodes an acetyltransferase involved in transcriptional regulation, was identified as the most important hub gene overlapping the networks of both APs. Then, we explored the genetically predicted EP300 expression levels in a cohort of 226 patients with first-episode psychosis who were being treated with APs to further assess the association of this gene with metabolic alterations. The EP300 expression levels were significantly associated with increases in body weight, body mass index, total cholesterol levels, low-density lipoprotein cholesterol levels and triglyceride concentrations after 6 months of AP treatment. Taken together, our analysis identified EP300 as a key gene in AP-induced metabolic abnormalities, indicating that the dysregulation of EP300 function could be important in the development of these side effects. However, more studies are needed to disentangle the role of this gene in the mechanism of action of APs.

The effect of ketogenic diet on serum lipid concentrations in children with medication resistant epilepsy

BackgroundKetogenic diet (KD) is a valuable treatment option for patients with medication-resistant epilepsy. It is associated with a number of side effects. However limited data are available for the long-term effects of KD on serum lipid levels. PurposeThe aim of this study was to investigate the long-term effects of KD on serum lipid concentrations in children with medication-resistant epilepsy in daily clinical practice. MethodA total of 73 children (40 girls) aged 3 to 193 months (median, 53 months) with medication-resistant epilepsy who received a KD treatment for at least 12 months between 2014 and 2019 years were enrolled in the study. All children were started on a KD with 3:1 ratio which was then adjusted between 2:1 to 4:1 after the onset of KD as clinically necessary. Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride concentrations and body mass index-standard deviation scores (BMI-SDS) were measured at onset and at 1, 6 and 12 months of treatment, and also in 40 of these patients they were measured at 18 and 24 months of treatment. ResultsDyslipidemia was observed in 71.2, 63, 63, 50, and 52.5% of the patients, at 1, 6, 12, 18, and 24 months, respectively. Median total cholesterol and triglyceride concentrations increased significantly at month-1, and although these high levels persisted for 24 months, the increase did not continue and showed a downward trend. However, this increase did not occur in the subset of patients with pre-existing dyslipidemia. Compared to baseline values, total cholesterol and triglyceride concentrations were higher at all time points, except 24-month cholesterol values. During the 24-month treatment period, BMI-SDS increased and the number of antiepileptic drugs decreased significantly. ConclusionTotal cholesterol and triglyceride concentrations appear to increase during the first month of KD treatment, and although these high values persist for 24 months, the increase does not continue, on the contrary, it approaches the normal values by drawing a downward trend. However, cholesterol and triglyceride concentrations do not increase in the subset of patients with pre-existing dyslipidemia.

Early-life associations between per- and polyfluoroalkyl substances and serum lipids in a longitudinal birth cohort

BackgroundExposures to per- and polyfluoroalkyl substances (PFASs) may affect metabolic outcomes, including lipid concentrations in the blood. However, few studies have evaluated potential associations between PFASs and lipids longitudinally. ObjectivesWe estimated associations between PFAS and lipid concentrations at birth and at several points in childhood. MethodsWe measured concentrations of five major PFASs in cord serum and in serum collected at 18 months, five years and nine years in 490 children from a prospective cohort in the Faroe Islands. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations were measured at birth, 18 months and nine years. We estimated associations between PFAS and lipid concentrations and evaluated possible effect modification by sex. We also tested whether PFAS associations with age-nine lipids varied by exposure period. ResultsSerum PFAS concentrations at ages five and nine were positively associated with lipid concentrations at age nine. Cross-sectional associations between PFASs and lipids at age nine were the strongest, with increases in serum concentrations of perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA) and perfluorooctanesulfonic acid (PFOS) associated with increases in TC, HDL-C and LDL-C. We found statistically significant differences in estimated PFAS effects by sex, where girls had stronger positive associations between PFASs and TC and LDL-C and boys had stronger positive associations with HDL-C. In repeated measure models, exposure period was a significant modifier of PFAS effects. ConclusionsOur findings suggest that childhood PFAS exposures may be associated with elevated serum lipid concentrations. This is a public health concern, as a detrimental lipid profile in childhood is a risk factor for later development of hyperlipidemia and cardiovascular disease.

Community-based management of complex type 2 diabetes: adaptation of an integrated model of care in a general practice setting.

Overburdened hospital clinics can have adverse outcomes. To evaluate the effectiveness and patient acceptability of an integrated model of complex type 2 diabetes care delivered in a community-based general practice by upskilled general practitioners (GP) co-located with an endocrinologist and diabetes nurse educator. Patients transferred from hospital clinic lists or referred by local GP were assessed in two southern Perth practices. An upskilled GP and endocrinologist developed a management plan which was communicated to the participant's usual GP. Up to two follow-up visits over 6 months ensured that management was acceptable and effective. A total of 464 people with type 2 diabetes (mean ± standard deviation age = 59.3 ± 13.7 years, 52.2% males) was enrolled. Their mean glycated haemoglobin (HbA1c ) was 9.3% (78 mmol/mol) and their mean body mass index 33.7 kg/m2 . Use of injectable blood glucose-lowering therapies increased between the initial and final visit in association with a median HbA1c reduction of 1.2% (13 mmol/mol) which was sustained to 12 months in assessable participants. There were also reductions in blood pressure, and serum low-density lipoprotein cholesterol and triglyceride concentrations. Patient satisfaction with current treatment, time for self-management, time spent in diabetes-related appointments and diabetes knowledge increased significantly. Non-attendance for scheduled appointments was <10%. Local hospital referrals and waiting lists reduced over the study period. This study confirms the value of integrated community-based care of complex type 2 diabetes which could represent a sustainable solution to overburdened hospital diabetes outpatient clinics.

Assessment of serum nitric oxide level in cigarette smoking

Background: Cigarette smoke has been implicated as a major risk factor in various diseases associated with endothelial dysfunction like essential hypertension, atherosclerosis and related cardiovascular dysfunction. Nitric oxide, an important second messanger plays a pivotal role in maintaining vasomotor tone and its level is also found to be altered in many chronic vascular disorders. The particulates in cigarette smoke is presumed to affect the production NO in vascular endothelium. Hence, it is proposed to study the effect of cigarette smoking in influencing Nitric oxide level. The study sample comprised of 138 chronic smokers and144 apparently healthy nonsmokers . Plasma glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and triglyceride concentration (TGL) were determined enzymatically and serum NO index (NOx) estimated by Griess method. It was found that serum NOx level was not influenced by biochemical parameters like plasma glucose and lipid profile. The estimated mean NOx levels was slightly lower in smokers(15.92 with SD 5.4) than in nonsmokers (16.66with SD 6.73) . However the difference was not statistically significant ( P= 0.31). It is concluded that there is no significant correlation between serum nitric oxide level and smoking, based on this study.

Rationale and design of a randomised controlled trial testing the effect of personalised diet in individuals with pre-diabetes or type 2 diabetes mellitus treated with metformin

IntroductionMetformin and diets aimed at promoting healthy body weight are the first line in treating type 2 diabetes mellitus (T2DM). Clinical practice, backed by clinical trials, suggests that many individuals...

Interactions Between Sugar-Sweetened Beverage Consumption and Genetic Variants in the ChREBP Locus on Lipoprotein Concentrations in the UK Biobank: A Replication Study

Abstract Objectives A meta-analysis of 11 CHARGE cohorts (N = 63,599) suggested that genetic variants within or near the CHREBP locus may modify the associations between sugar sweetened beverage (SSB) consumption and high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. The study objective was to replicate these findings in a large independent cohort. Methods Blood lipids and 24-hour recalls were available for 57,794 adults of European ancestry in the UK Biobank (2006-‘10). SSBs included “squash” and “fizzy” drinks derived from a single 24-hr recall. A total of 875 SNPs within or near the CHREBP locus were identified and included in this analysis. Associations between these SNPs and HDL-C and TG concentrations were quantified among participants who did not report SSB consumption (non-consumers, n = 45,866), reported ≥0.5 servings/day of SSB (consumers, n = 11,928), and a subset of consumers who reported ≥2 servings/day of SSB (high consumers, n = 3742). Interaction between SSB and selected SNPs on HDL-C and TG concentrations was evaluated by examining the difference in beta coefficients between strata. Results were considered statistically significant at a Bonferroni-corrected pinteract &amp;lt; 0.0001 (0.05/499 effective tests). Results A significant interaction between SSB consumption and TBL2-rs71556729 on HDL-C concentration previously observed in the meta-analysis was replicated in UK Biobank. However, we observed a stronger interaction for a SNP in high linkage disequilibrium (R2 = 0.93) FZD9-rs34821369 (MAF = 0.03, pinteract = 8.2E-05) with TBL2-rs71556729 (MAF = 0.03, pinteract = 0.0004). Among only SSB consumers, each additional minor G allele at FZD9-rs34821369 was associated with mean HDL-C concentrations 1.63 mg/dL (SE = 0.53, P = 0.002) higher than those with the major T allele. Conclusions Our results suggest that adults with the minor allele at FZD9-rs34821369 may be protected against SSB-induced low HDL-C concentrations. These results are consistent the findings from a prior meta-analysis of 11 cohorts. Funding Sources NIH, AHA, USDA-ARS. This research has been conducted using the UK Biobank Resource (Application Number 35,835).

P5366Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Abstract Background The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described. Hypothesis EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI. Methods Data on coronary artery plaques from 121 patients presenting with acute coronary syndrome or stable angina who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no-EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI. Results We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low-density lipoprotein cholesterol concentration, triglyceride concentration, and high-density lipoprotein cholesterol concentration). The EPA group had significantly lower mean lipid index (818±806 vs. 1,574±891) and macrophage grade (13.5±5.9 vs. 19.3±7.4) but higher mean minimum fibrous cap thickness (109.2±55.7 vs. 81.6±36.4 μm) than the no-EPA group (P=0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P=0.043 and 0.024, respectively). Conclusion This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI. Acknowledgement/Funding None

Serum pentraxin 3 concentration in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes (T2D). Pentraxin 3 (PTX3), a marker of inflammation, is a cardiovascular risk factor. We examined clinical and biochemical factors associated with serum PTX3 concentrations in patients with T2D with and without NAFLD. Serum material was obtained from 116 patients with T2D (mean age, 59.1 years), including 79 patients with NAFLD. Median (interquartile range) PTX3 level was 4.264 (2.293) ng/ml in patients with and 3.773 (3.223) ng/ml in patients without NAFLD (P = 0.93). In the whole group, PTX3 level was associated with total cholesterol, low‑density lipoprotein cholesterol (LDL‑C), apolipoprotein (apo) B100, apo C3, triglyceride (TG) concentrations, and waist circumference after adjustment for age and gender. As indicated by partial regression coefficient b, increase of independent variable LDL‑C by 1 mmol/l was associated with the rise of PTX3 by 1.2017 ng/ml, increase of apo B100 by 1 mg/dl with the rise of PTX3 by 1.0051 ng/ml, and increase of apo C3 by 1 μg/dl with the rise of PTX3 by 1.0012 ng/ml. In patients with T2D with NAFLD, total cholesterol, LDL‑C, TG, apo C3, and apo B100 were associated with PTX3. Associations of PTX3 with apolipoproteins were observed only in the NAFLD group. Reported associations of PTX3 level add new insight into possible mechanisms of its atherogenic actions.