Changes In Triglyceride Levels Research Articles

Epigenome wide association study of SNP\u2013CpG\xa0interactions on changes in triglyceride levels after pharmaceutical intervention: a GAW20 analysis

In the search for an understanding of how genetic variation contributes to the heritability of common human disease, the potential role of epigenetic factors, such as methylation, is being explored with increasing frequency. Although standard analyses test for associations between methylation levels at individual cytosine-phosphate-guanine (CpG) sites and phenotypes of interest, some investigators have begun testing for methylation and how methylation may modulate the effects of genetic polymorphisms on phenotypes. In our analysis, we used both a genome-wide and candidate gene approach to investigate potential single-nucleotide polymorphism (SNP)–CpG interactions on changes in triglyceride levels. Although we were able to identify numerous loci of interest when using an exploratory significance threshold, we did not identify any significant interactions using a strict genome-wide significance threshold. We were also able to identify numerous loci using the candidate gene approach, in which we focused on 18 genes with prior evidence of association of triglyceride levels. In particular, we identified GALNT2 loci as containing potential CpG sites that moderate the impact of genetic polymorphisms on triglyceride levels. Further work is needed to provide clear guidance on analytic strategies for testing SNP–CpG interactions, although leveraging prior biological understanding may be needed to improve statistical power in data sets with smaller sample sizes.

Do changes in DNA methylation mediate or interact with SNP variation? A pharmacoepigenetic analysis

BackgroundIn studies with multi-omics data available, there is an opportunity to investigate interdependent mechanisms of biological causality. The GAW20 data set includes both DNA genotype and methylation measures before and after fenofibrate treatment. Using change in triglyceride (TG) levels pre- to posttreatment as outcome, we present a mediation analysis that incorporates methylation. This approach allows us to simultaneously consider a mediation hypothesis that genotype affects change in TG level by means of its effect on methylation, and an interaction hypothesis that the effect of change in methylation on change in TG levels differs by genotype. We select 322 single-nucleotide polymorphism–cytosine-phosphate-guanine (SNP-CpG) site pairs for mediation analysis on the basis of proximity and marginal genome-wide association study (GWAS) and epigenome-wide association study (EWAS) significance, and present results from the real-data sample of 407 individuals with complete genotype, methylation, TG levels, and covariate data.ResultsWe identified 3 SNP-CpG site pairs with significant interaction effects at a Bonferroni-corrected significance threshold of 1.55E-4. None of the analyzed sites showed significant evidence of mediation. Power analysis by simulation showed that a sample size of at least 19,500 is needed to detect nominally significant indirect effects with true effect sizes equal to the point estimates at the locus with strongest evidence of mediation.ConclusionsThese results suggest that there is stronger evidence for interaction between genotype and methylation on change in triglycerides than for methylation mediating the effect of genotype.

Evaluating the performance of gene-based tests of genetic association when testing for association between methylation and change in triglyceride levels at GAW20

Although methylation data continues to rise in popularity, much is still unknown about how to best analyze methylation data in genome-wide analysis contexts. Given continuing interest in gene-based tests for next-generation sequencing data, we evaluated the performance of novel gene-based test statistics on simulated data from GAW20. Our analysis suggests that most of the gene-based tests are detecting real signals and maintaining the Type I error rate. The minimum p value and threshold-based tests performed well compared to single-marker tests in many cases, especially when the number of variants was relatively large with few true causal variants in the set.

Network analysis of drug effect on triglyceride-associated DNA methylation

BackgroundDNA methylation, an epigenetic modification, can be affected by environmental factors and thus regulate gene expression levels that can lead to alterations of certain phenotypes. Network analysis has been used successfully to discover gene sets that are expressed differently across multiple disease states and suggest possible pathways of disease progression. We applied this framework to compare DNA methylation levels before and after lipid-lowering medication and to identify modules that differ topologically between the two time points, revealing the association between lipid medication and these triglyceride-related methylation sites.MethodsWe performed quality control using beta-mixture quantile normalization on 463,995 cytosine-phosphate-guanine (CpG) sites and deleted problematic sites, resulting in 423,004 probes. We identified 14,850 probes that were nominally associated with triglycerides prior to treatment and performed weighted gene correlation network analysis (WGCNA) to construct pre- and posttreatment methylation networks of these probes. We then applied both WGCNA module preservation and generalized Hamming distance (GHD) to identify modules with topological differences between the pre- and posttreatment. For modules with structural changes between 2 time points, we performed pathway-enrichment analysis to gain further insight into the biological function of the genes from these modules.ResultsSix triglyceride-associated modules were identified using pretreatment methylation probes. The same 3 modules were not preserved in posttreatment data using both the module-preservation and the GHD methods. Top-enriched pathways for the 3 differentially methylated modules are sphingolipid signaling pathway, proteoglycans in cancer, and metabolic pathways (p values < 0.005). One module in particular included an enrichment of lipid-related pathways among the top results.ConclusionsThe same 3 modules, which were differentially methylated between pre- and posttreatment, were identified using both WGCNA module-preservation and GHD methods. Pathway analysis revealed that triglyceride-associated modules contain groups of genes that are involved in lipid signaling and metabolism. These 3 modules may provide insight into the effect of fenofibrate on changes in triglyceride levels and these methylation sites.

Maternal Postprandial Triglycerides in the Home Setting

Background and Aims: Elevated maternal triglycerides (TG) have been associated with adverse pregnancy outcomes including an increased risk of preeclampsia and macrosomia. Maternal TG are primarily measured in the fasting state and at single time points during pregnancy. Temporal and prandial changes in TG levels during pregnancy are not well described. The purpose of this study was to examine flux of capillary glucose and TG in late pregnancy, how they are influenced by high and low fat meals, and whether they relate to infant body composition. Materials and Methods: Women in the third trimester of pregnancy completed 4 days of home capillary glucose and TG monitoring (4 times a day (fasting and two hours post each meal)). Using the Roche Accutrend Plus meter. Each woman consumed an isocaloric high fat (41%) and a low fat (25%) breakfast meal on different days during the study period. Area under the curve (AUC) for the capillary glucose and TG measures after the standardized meals was calculated using trapezoidal approximation. AUC for women with and without GDM was compared for each meal and metabolic measure. Infant body fat % was measured by air displacement plethysmography. Results: To date, thirteen women, 7 with GDM and 6 normoglycaemic have completed the study. Median capillary glucose levels: fasting 5.0 (95% CI 4.6-5.2) mmol/L and postprandial 6.0 (95% CI 5.7-6.2) mmol/L. Median capillary TG: fasting 3.3 (95% CI 2.9-3.8) mmol/L and postprandial 3.6 (95% CI 3.2-3.8) mmol/L. Mean infant body fat % 10.6 (SD4.9)%. There were no significant differences in capillary glucose or triglycerides between the meals although capillary glucose trended higher with the low fat meal. GDM status did not affect the AUC glucose or AUC triglycerides for either meal. Conclusion: This study demonstrates that capillary triglycerides can be monitored at home in a similar fashion to capillary glucose. Capillary triglyceride levels were not related to infant anthropometry and did not vary significantly with meal fat content. Recruitment is ongoing. Disclosure H.L. Barrett: None. M. Dekker: Speaker's Bureau; Self; Abbott. Other Relationship; Self; Nestlé. S.J. de Jersey: None. M.C. d'Emden: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation. L. Callaway: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy.

Effects of Treatment with Adalimumab on Blood Lipid Levels and Atherosclerosis in Patients with Rheumatoid Arthritis

BackgroundTreatment with tumor necrosis factor inhibitors for rheumatoid arthritis has been associated with a decreased risk of cardiovascular disease in observational studies. There are conflicting data on the influence of tumor necrosis factor inhibitors on lipid levels.ObjectivesTo evaluate the effect of treatment with adalimumab on blood lipid levels, lipoproteins, and atherosclerosis of the carotid artery.MethodsFourteen patients with active rheumatoid arthritis (11 women and 3 men; mean age 63.7 years; median disease duration 9.0 years; and 78% rheumatoid factor positive) were treated with adalimumab 40 mg subcutaneously every 2 weeks and followed for 3 months. The patients had not been treated with adalimumab previously and had not received other tumor necrosis factor inhibitors within the past 3 months or moderate/high dose corticosteroids within the past 2 weeks. The intima-media thickness of the common carotid artery was assessed using B mode ultrasonography. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol levels were analyzed in fresh fasting blood samples, whereas apolipoprotein B and apolipoprotein A1 (apoA1) levels were determined in thawed plasma samples using standard turbidimetric immunoassays.ResultsTotal cholesterol (mean = 5.36 vs 5.96 mmol/L; P = 0.005), LDL cholesterol (mean = 3.33 vs 3.77 mmol/L; P = .005), HDL cholesterol (mean = 1.43 vs 1.55 mmol/L; P = 0.048), apolipoprotein B (mean = 1.04 vs 1.13 g/L; P = .012), and apoA1 (mean = 1.42 vs 1.58 g/L; P = 0.005) all increased, but there were no major changes in the LDL to HDL cholesterol ratio (median = 2.56 vs 2.35; P = 0.27) or the apolipoprotein B to apoA1 ratio (mean = 0.76 vs 0.74; P = 0.46). There was no change in triglyceride levels (P = 0.55). Disease activity decreased significantly from baseline to the 3-month evaluation (disease activity score based on 28 joints mean = 5.6 vs 4.1; P = 0.007). An increase in apoA1 correlated with decreases in the patient global assessment of disease severity (r = 0.79; P = 0.001) and C-reactive protein level (r = 0.74; P = 0.003). Changes in the apoliprotein B to apoA1 ratio correlated with changes in erythrocyte sedimentation rate (r = 0.54; P = 0.046). There was no major change in the common carotid artery intima-media thickness (mean = 0.78 vs 0.80 mm; P = 0.48).ConclusionsAlthough these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery.

Allium vegetable intakes and the incidence of cardiovascular disease, hypertension, chronic kidney disease, and type 2 diabetes in adults: a longitudinal follow-up study.

This study investigated the association between habitual consumption of allium vegetables (garlic and onion) and the incidence of cardiovascular disease (CVD) outcomes, hypertension (HTN), chronic kidney disease (CKD), and type 2 diabetes (T2D). Adult men and women, participated in the Tehran Lipid and Glucose Study (2006-2008 to 2012-2014), were recruited. Habitual dietary intakes were assessed using a validated semiquantitative food frequency questionnaire. Demographics, anthropometrics, blood pressure, and biochemical variables were evaluated at baseline and during follow-up examinations. Multivariate Cox proportional hazard regression models adjusted for potential confounders were used to estimate the development of CVD outcomes, HTN, CKD, and T2D in relation to allium vegetable intakes. Mean age of participants (44.2% men) was 40.3 ± 14.3 years, at baseline. During an average of 6 years of follow-up, the incidence rate of CVD outcomes, HTN, CKD, and T2D were 3.3, 15.5, 17.9, and 6.7%, respectively. A higher habitual intake of allium vegetables was associated with a 64% reduced risk of CVD outcomes (hazard ratio = 0.36, 95% confidence interval, CI = 0.18-0.71; P for trend = 0.011), 32% lower incidence of CKD (hazard ratio = 0.69, 95% CI = 0.46-0.98; P for trend = 0.11), and 26% decreased HTN development (hazard ratio = 0.74, 95% CI = 0.54-1.00; P for trend = 0.06). No significant association was observed between allium vegetable intakes and the risk of T2D. Allium vegetable intake was related to 6 years' changes of triglyceride levels (β = -0.81, P = 0.01) and creatinine clearance (β = 0.56, P = 0.01). Data of the current study support the available mechanistic findings regarding cardiorenal protective properties of allium vegetables.

Effect of Green Tea Ingestion on Postprandial Triglyceride Levels in Young Women

Introduction: High blood triglyceride (TG) level is a risk factor for cardiovascular disease. Green tea, as a beverage, may reduce postprandial blood TG level through inhibition of fat absorption in the intestinal lumen. The aim of this study was to assess the difference of postprandial blood TG level changes between treatment group (high-fat meal and green tea beverage containing 738 mg of catechins) and control group (high-fat meal and plain water containing 0 mg of catechins).Methods: The study was a randomized, single-blind, parallel-group clinical trial including 40 healthy young women. Blood was collected immediately before the meal and then at 2 and 4 h thereafter of each group. Method of TG measurement: GPO-PAP, using Beckman CX 5-CE machine and Good’s buffer reagent.Results: Postprandial blood TG level at 4 h in the treatment group was significantly lower compared to the control group (1.00 ± 0.27 vs. 1.22 ± 0.34 mmol/L, p = 0.03). The change in blood TG level from baseline to 4 h postprandial was also significantly lower in the treatment group compared to the control group (0.21 ± 0.14 vs. 0.37 ± 0.26 mmol/L, p = 0.02).Conclusion: It was concluded that green tea ingestion during high fat meal suppressed postprandial elevation of TG 4 hour after meal.

The DRD3 Ser9Gly Polymorphism Predicted Metabolic Change in Drug-Naive Patients With Bipolar II Disorder.

Patients with bipolar II disorder (BDII) have a higher prevalence rate of metabolic disturbance. Whether BDII itself, in addition to its current standard treatment, is a risk factor for metabolic syndrome warrants additional study. The dopamine receptor D3 (DRD3) gene, one of the candidate genes for BDII, is also involved in the dopaminergic system. We investigated whether it is related to changes in the metabolic indices of patients with BDII given 12 weeks of standard treatment.Patients with a first diagnosis of BDII (n = 117) were recruited. Metabolic profiles (cholesterol, triglycerides, fasting serum glucose, body mass index) were measured at baseline and at 2, 8, and 12 weeks. The genotype of the DRD3 Ser9Gly polymorphism (rs6280) was determined. Multiple linear regressions with generalized estimating equation methods were used.Seventy-six (65.0%) patients completed the 12-week intervention. Significant differences in triglyceride change were associated with the DRD3 Ser9Gly genotype (P = 0.03). Patients with the Ser/Ser genotype had significantly smaller triglyceride increases and a lower risk of developing metabolic syndrome than did those with the Ser/Gly+Gly/Gly genotype. However, the associations between the DRD3 Ser9Gly polymorphism with changes in triglyceride level become nonsignificant after correcting for multiple comparisons.We conclude that the DRD3 Ser9Gly polymorphism is nominally associated with changes in triglycerides and metabolic syndrome after 12 weeks of standard BDII treatment.

Objectively Measured Aerobic and Resistance Exercise and Cardiovascular Disease Risk Factor Response

PURPOSE: To examine the effects of objectively measured weekly exercise weight (EW) lifted and exercise heart beats (EHB) during exercise training on changes in cardiovascular disease (CVD) risk factors. METHODS: We randomized 31 pre-to-stage 1 hypertensive (not on medication), overweight/obese, and sedentary non-smokers (58±8 years) into an aerobic training (AT) only (n=16) or a resistance training (RT) only (n=15) 8 week exercise intervention. Participants exercised 3 days/week for 60 min/session. An innovative exercise training system and software (TechnoGym) captured EW lifted and EHB automatically each session. Total weekly EW lifted was calculated as the sum of weight x repetitions x sets for each exercise, averaged over 8 weeks, then divided by body weight (lbs). Total weekly EHB were calculated by the sum of exercise heart rate x min/session/week, with resting heart rate x minutes of exercise subtracted. We measured peripheral and central blood pressure (BP), % body fat, cardiorespiratory fitness, bench and leg press 1 repetition maximum (1RM), and blood lipids at baseline and 8-weeks. Individual CVD risk factors were standardized as sex specific z-scores for each participant and the mean was used to establish an overall clustered CVD risk score. Data was analyzed using Pearson correlation and linear mixed models adjusting for age, sex, and average daily steps. RESULTS: The average weekly EW and EHB were 220±68 lbs and 7004±1419 beats, respectively. Regression analysis showed a reduction in overall CVD risk score by -0.25 (p = 0.06) per 100 lbs lifted relative to body weight with RT and -0.1 (p=0.16) per 1000 beats with AT. With RT, we found strong correlations between total EW and changes in peripheral systolic (r=-0.45, p=0.09) and diastolic BP (r=-0.59, p=0.02), central systolic (r=-0.47, p=0.08) and diastolic BP (r=-0.53, p=0.04), and leg press 1RM (r=0.62, p=0.01). With AT, strong correlations with total EHB were noted with change in triglyceride levels (r=-0.50, p=0.049). CONCLUSIONS: In individuals at high risk of developing CVD, increased total EW lifted and EHB are associated with improved overall CVD risk, especially peripheral and central BP with greater EW lifted, and triglyceride levels for additional EHB. Supported by Iowa State University College of Human Sciences seed grant.

The pattern of lipids and lipoproteins during the menopausal transition in Chinese women

Objective To investigate changes in levels of lipids and lipoproteins in Chinese women during perimenopause and postmenopause as primary study endpoints, for the first time including lipoprotein(a).Methods The retrospective study was performed in 1015 women without hormone therapy aged 34–76 years from 20 provinces of China who visited the Beijing Obstetrics & Gynecology hospital. Menopausal status was defined by the criteria of the 2011 Stages of Reproductive Aging Workshop.Results Levels of total cholesterol, triglycerides and low density lipoprotein (LDL) cholesterol increased and that of high density lipoprotein (HDL) cholesterol decreased in the postmenopausal compared to the perimenopausal group. In the women with body mass index (BMI) ≥ 25 kg/m2, total cholesterol and LDL cholesterol increased, HDL cholesterol decreased and changes in triglyceride levels were not significant. In the women with BMI < 25 kg/m2, the increase in triglyceride levels during the transition was significant. Changes in lipoprotein(a), apolipoprotein A1 and apolipoprotein B were not significant. Comparing the groups with BMI ≥ 25 kg/m2 vs. BMI < 25 kg/m2, only the differences for apolipoprotein A1 and for triglycerides were significant. Triglycerides correlated positively with follicle stimulating hormone and BMI, and total cholesterol correlated positively with follicle stimulating hormone and age (all p < 0.05).Conclusions Some changes in lipids can be related to menopausal status, some to increasing age, some to both; especially triglycerides and apolipoprotein A1 were found also to be related to BMI. Surprisingly lipoprotein(a) did not change either with increasing age or during the transition despite known possible interference with estrogenic status.

Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: a prospective cohort study.

BackgroundPrevious studies have shown that angiopoietin-like protein 8 (ANGPTL8), also called as betatrophin, acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis. Moreover, ANGPTL8 promotes proliferation of pancreatic β-cells and induces insulin secretion. However, there are no previous longitudinal studies in humans.MethodsWe analyzed the age- and sex-matched data of 240 normal weight and overweight Korean children from the Korean Metabolic disorders and Obesity Study in Elementary School children (K-MOSES), a prospective observational cohort study.ResultsAt baseline, ANGPTL8 concentrations were positively associated with triglycerides (TG) (r = 0.168, P = 0.010), whereas ANGPTL3 levels were associated with fasting insulin (r = 0.248, P < 0.001) and the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.197, P = 0.002). Although both ANGPTL8 and ANGPTL3 levels did not differ between children with normal weight and children with overweight, ANGPTL8 levels were increased in males compared to females (341.2 [267.4–436.5] vs. 270.2 [213.9–378.8] pg/ml, P = 0.001). In particular, there was no significant inter-relationship between circulating ANGPTL8 and ANGPTL3 concentrations in Korean boys and girls (r = −0.073, P = 0.265). Multivariate analysis showed that baseline ANGPTL8 concentrations were independently associated with future changes of serum TG levels in Korean children after adjusting for confounding factors after a 3 year follow-up period (r = −0.165, P = 0.016).ConclusionsThis longitudinal study demonstrated for the first time that baseline ANGPTL8 levels were associated with baseline and future changes in TG levels in Korean children.

Beneficial effects of melatonin and alpha lipoic acid on lopinavir/ ritonavir-induced alterations in serum lipid and glucose levels of male albino rats

The use of lopinavir/ritonavir (LPV/r) has been associated with alterations in serum lipid and glucose levels. This study was designed to investigate the effects of melatonin (MT) and alpha lipoic acid (ALA) on LPV/r-induced changes in serum levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and glucose (GL) levels in male albino rats. Rats in group A1 (placebo control) and group A2 (solvent control) were orally treated with normal saline and 1% ethanol respectively. Groups B-F contained 15 rats each which were divided into 3 groups of 5 rats each. Rats in group B were orally treated with MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and a combination of MT and ALA, accordingly. Rats in group C were orally treated with 22.9/5.71, 45.6/11.4 and 91.4/22.9 mg kg-1/day of LPV/r, accordingly. Rats in groups D-F were orally treated with MT (10 mg kg-1/ day), ALA (10 mg kg-1/day) and combined doses of ALA and MT before oral treatment with 22.9/5.71, 45.6/11.4 and 91.4/22.9 mg kg-1/day of LPV/r, accordingly. All rats were treated for 30 days and at the end of the drug treatment, the serum levels of lipid fractions and glucose were evaluated. Treatment with MT and ALA significantly (p&lt;0.05) decreased baseline serum levels of TG, TC, VLDL-C, LDL-C and GL, but these parameters were significantly (p&lt;0.05) increased in a dose-dependent manner in LPV/r-treated rats when compared to placebo control. Administration of MT and ALA prior to treatment with LPV/r significantly (p&lt;0.05) decreased serum levels of TG, TC, VLDL-C, LDL-C and GL when compared to LPV/r-treated rats. However, decreases obtained in rats pretreated with combined doses of MT and ALA were significantly (p&lt;0.05) different when compared to their individual doses. This study showed that MT and ALA can serve as remedies for LPV/r-induced alterations in serum lipid and glucose levels.

Changes in triglyceride levels in ultra-high risk for psychosis individuals treated with omega-3 fatty acids.

The aim of this analysis was to assess changes in lipid parameters, specifically in triglyceride (TG) levels, in a population at ultra-high risk (UHR) for psychosis treated with ω-3 polyunsaturated fatty acids (PUFAs) versus placebo. Data were derived from a randomized, double-blind, placebo-controlled trial conducted at an early psychosis unit. Eighty-one individuals, aged 13-25 years, at UHR for psychosis participated in a 12-week intervention trial of 1.2 g/day of ω-3 PUFAs (n = 41) versus placebo (n = 40). Lipid and C-reactive protein levels were collected at baseline and after 12 weeks. Between-group comparisons showed no significant difference in TG levels after the intervention. However, in individuals with baseline TG levels above 150 mg dL-1 there was a significant mean TG reduction of 67.29 (SD 42.54; P = 0.006) in the ω-3 group (n = 7). In this sample of UHR individuals, a 12-week intervention with ω-3 PUFAs was effective in reducing previously elevated TG levels. This might introduce the possibility of altering the lipid profile and thus the risk of cardiovascular morbidity of UHR individuals.

Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.

Although a postprandial increment in triglyceride (TG) levels is considered to be a risk factor for atherogenesis, tests (e.g., fat load) to assess postprandial changes in TG levels cannot be easily applied to clinical practice. Therefore, fasting markers that predict postprandial TG states are needed to be developed. One current candidate is lipoprotein lipase (LPL) protein, a molecule that hydrides TGs. This study investigated whether fasting LPL levels could predict postprandial TG levels. A total of 17 subjects (11 men, 6 women, mean age 52 ± 11 years) with normotriglyceridemia during fasting underwent the meal test. Several fasting parameters, including LPL, were measured for the area under the curve of postprandial TGs (AUC-TG). The subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was 41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after two postprandial hours). Stepwise multiple regression analysis demonstrated that fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass levels were found to be a predictor of the AUC-TG (β = 0.65, P < 0.01), and this relationship was independent of fasting TG levels. Fasting LPL levels may be useful to predict postprandial TG increment in this population.

Changes in Plasma Phospholipid Fatty Acid Patterns and their Impact on Plasma Triglyceride Levels Following Fish Oil Supplementation

The objective of the present study was to test for associations between changes in fatty acids (FAs) and changes in plasma triglyceride (TG) levels after an n-3 FA supplementation and to test whether SNPs from the FADS gene cluster were associ- ated with plasma FA levels or with specific FA patterns. A total of 210 subjects completed a 2-wk run-in period followed by 6-wk supplementation with 5g/d of fish oil. FA profiles of plasma phospholipids (PPLs) were obtained and 19 SNPs from the FADS gene cluster were genotyped. Principal component analysis was conducted and scores were calculated. There was an increase in EPA, DPA and DHA levels in PPLs as well as a decrease in ALA and all n-6 FA levels after the supplementa- tion. Factor analysis suggested 4 post-n-3 FA supplementation patterns. Changes in AA, ALA, DGLA, as well as changes in total n-3 and omega-6 FAs in absolute quantities of FAs were all associated with a change in TG levels whereas the cor- relation remained significant only for AA and DGLA when FAs were expressed as percentage of total FAs. Several SNPs from the FADS gene cluster were associated with post-supplementation FA levels. These results suggest that FAs alone or regrouped in factors could play a role in modulating plasma TG levels after fish oil supplementation. SNPs from the FADS gene cluster interact with both FAs and/or factors to modulate TG levels.

Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study.

AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up. At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA >50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL). After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm(3); P = 0.002) and Week 144 (+94 cells/mm(3); P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m(2); P < 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (-1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients. Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.

Comparison of the Effects of Eicosapentaenoic Acid With Docosahexaenoic Acid on the Level of Serum Lipoproteins in Helicobacter pylori: A Randomized Clinical Trial.

Background:Helicobacter pylori infection is the most common chronic bacterial infection around the world and an important cause of gastrointestinal disorders, which might be involved in the pathogenesis of some extragastrointestinal disturbances as well as changes in serum lipid profile. Hypolipemic properties of omega-3 fatty acids have been studied in several studies.Objectives:The present study aimed to compare the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on the level of serum lipoproteins in H. pylori.Patients and Methods:In a randomized, double-blinded, placebo-controlled clinical trial in Iran, 105 Helicobacter pylori were randomly allocated to receive 2 g of daily EPA (35 patients), DHA (35 patients), or medium-chain triglyceride (MCT) oil as placebo (33 patients) along with conventional tetra-drug H. pylori eradication regimen for 12 weeks.Results:From 105 included patients, 97 (31 in EPA, 33 in DHA, and 33 in control groups) completed the study and were included in final analysis. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and the ratios of TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C were not significantly different among the three groups, while the level of triglyceride (TG) was statistically different. DHA (-16.6 ± 30.34) and control (+ 15.32 ± 56.47) groups were statistically different with regard to changes in TG levels (P = 0.000).Conclusions:There was no difference between the effects of 2 g of EPA or DHA supplementation for 12 weeks on the levels of total cholesterol, LDL-C, HDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C; however, it had a desirable effect on the level of TG in a way that the effect of DHA was clearer.

Does mirtazapine interfere with naturalistic diabetes treatment?

Mirtazapine is known to induce weight gain and possibly leads to exacerbation of diabetic profiles. However, many cases of diabetic patients, who complained of insomnia and depression, were treated with mirtazapine in the clinical situations. Thus, this study aimed to assess any negative effects that treatment with mirtazapine may incur in diabetic patients.This study included 33 patients enrolled in naturalistic diabetes treatment that had also been diagnosed with depression and prescribed mirtazapine for at least 6 months. Another 33 diabetic patients who had not taken any psychiatric medicines were included as a control group. Body mass index, fasting plasma glucose, HbA1c, total cholesterol, triglyceride levels, high-density lipoprotein, and low-density lipoprotein were assessed at baseline, 3 months, and 6 months.The dose of mirtazapine at baseline was 24.3 ± 14.0 mg/d in the mirtazapine group, and the 2 groups did not differ in any baseline characteristics except for total cholesterol levels. Body mass index increased in both groups, and the change in the mirtazapine group (1.0 ± 0.6 kg/m) was significantly greater than that in the control group (0.3 ± 0.4 kg/m, P < 0.001) at 6 months. Only the control group exhibited a decrease in fasting plasma glucose, whereas both groups showed a decrease in HbA1c, low-density lipoprotein, and total cholesterol, an increase in high-density lipoprotein, and no change in triglyceride levels. None of the differences between the groups were statistically significant.In conclusion, mirtazapine increased the weight gain of diabetic patients; however, other diabetic and lipid markers generally did not worsen during the 6-month treatment period. These results suggest that, at least in the short term, mirtazapine is safe for diabetic patients in a stable state and are undergoing appropriate diabetic treatment.

Indicadores antropométricos associados a hipertrigliceridemia na predição de gordura visceral

The accumulation of visceral fat is strongly associated with cardiometabolic changes. Alternative methods, such as the association between anthropometric indicators and hypertriglyceridemia, are used as the best estimate for the accumulation of visceral fat, preventing cardiovascular diseases. The aim of this study was to evaluate the association of anthropometric indicators with hypertriglyceridemia in the prediction of visceral fat in men and women. This was a cross-sectional study conducted with 192 individuals, of both genders, submitted to anthropometric evaluation (sagittal abdominal diameter [SAD], waist circumference [WC], and waist-hip ratio [WHR]), serum dosage of triglycerides (TG), and computed tomography scan, in order to measure the visceral adipose tissue (VAT) area. Descriptive analysis, Pearson’s Correlation, and multiple linear regression were performed. Anthropometric indicators had high correlation with the VAT area (p=0.000). Regardless of serum TG levels, individuals with high values of anthropometric indicators had excess VAT area (p&lt;0.05). For every centimeter increased in SAD, there was an average increase of 12.46 cm² in the VAT area. The study showed that both SAD and WC were good indicators to explain the variability in the VAT area, independently of changes in TG levels, making it possible to identify individuals with a risk of developing cardiovascular diseases.