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Metabolite Changes After Metabolic Surgery - Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels.
Ahlin, S, Cefalo, C, Bondia-Pons, I, Trošt, K, Capristo, E, Marini, L, Romero, M, Zorzano, A, Gastaldelli, A, Mingrone, G, et al
Frontiers in endocrinology. 2021;:786952
Abstract
AIMS: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. MATERIALS AND METHODS This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). RESULTS Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. CONCLUSIONS Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.
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Body Fat Distribution and Metabolic Changes in a Cohort of Adolescents Living With HIV Switched to an Antiretroviral Regimen Containing Dolutegravir.
Giacomet, V, Lazzarin, S, Manzo, A, Paradiso, L, Maruca, K, Barera, G, Zuccotti, GV, Mora, S
The Pediatric infectious disease journal. 2021;(5):457-459
Abstract
Use of antiretrovirals is associated to body fat accumulation. We measured body composition in adolescents living with HIV switched to a dolutegravir-containing regimen. Trunk fat and trunk/body fat ratio markedly increased after 12 months. Total and low density lipoprotein cholesterol decreased after 3 months. Increase in trunk fat may put at risk of future cardiovascular problems, despite improvement in the lipid profile.
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Human intestinal lipid storage through sequential meals reveals faster dinner appearance is associated with hyperlipidemia.
Jacome-Sosa, M, Hu, Q, Manrique-Acevedo, CM, Phair, RD, Parks, EJ
JCI insight. 2021;(15)
Abstract
BackgroundIt is increasingly recognized that intestinal cells can store lipids after a meal, yet the effect of this phenomenon on lipid absorption patterns in insulin resistance remains unknown.MethodsThe kinetics of meal fat appearance were measured in insulin-sensitive (IS, n = 8) and insulin-resistant (IR, n = 8) subjects after sequential, isotopically labeled lunch and dinner meals. Plasma dynamics on triacylglycerol-rich (TAG-rich) lipoproteins and plasma hormones were analyzed using a nonlinear, non-steady state kinetic model.ResultsAt the onset of dinner, IS subjects showed an abrupt plasma appearance of lunch lipid consistent with the "second-meal effect," followed by slower appearance of dinner fat in plasma, resulting in reduced accumulation of dinner TAG of 48% compared with lunch. By contrast, IR subjects exhibited faster meal TAG appearance rates after both lunch and dinner. This effect of lower enterocyte storage between meals was associated with greater nocturnal and next-morning hyperlipidemia. The biochemical data and the kinetic analysis of second-meal effect dynamics are consistent with rapid secretion of stored TAG bypassing lipolysis and resynthesis. In addition, the data are consistent with a role for the diurnal pattern of plasma leptin in regulating the processing of dietary lipid.ConclusionThese data support the concept that intestinal lipid storage may be physiologically beneficial in IS subjects.Trial registrationClinicalTrials.gov NCT02020343.FundingThis study was supported by a grant from the American Diabetes Association (grant 1-13-TS-12).
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Direct oral anticoagulants and vitamin K antagonists are linked to differential profiles of cardiac function and lipid metabolism.
Eggebrecht, L, Prochaska, JH, Tröbs, SO, Schwuchow-Thonke, S, Göbel, S, Diestelmeier, S, Schulz, A, Arnold, N, Panova-Noeva, M, Koeck, T, et al
Clinical research in cardiology : official journal of the German Cardiac Society. 2019;(7):787-796
Abstract
BACKGROUND Experimental data indicate that direct acting oral anticoagulants (DOAC) and vitamin K antagonists (VKA) may exert differential effects on cardiovascular disease. METHODS Data from the prospective, observational, single-center MyoVasc Study were used to examine associations of DOAC as compared to VKA with subclinical markers of cardiovascular disease, cardiac function, and humoral biomarkers in heart failure (HF). RESULTS Multivariable analysis adjusted for age, sex, traditional cardiovascular risk factors, comorbidities, and medications with correction for multiple testing demonstrated that DOAC therapy was among all investigated parameters an independent significant predictor of better diastolic function (E/E': β - 0.24 [- 0.36/- 0.12]; P < 0.0001) and higher levels of ApoA1 (β + 0.11 g/L [0.036/0.18]; P = 0.0038) compared to VKA therapy. In propensity score-weighted analyses, the most pronounced differences between DOAC and VKA-based therapy were also observed for E/E' (∆ - 2.36) and ApoA1 (∆ + 0.06 g/L). Sensitivity analyses in more homogeneous subsamples of (i) individuals with AF and (ii) individuals with asymptomatic HF confirmed the consistency and robustness of these findings. In the comparison of factor IIa and Xa-directed oral anticoagulation, no differences were observed regarding cardiac function (E/E' ratio: βIIa inhibitor - 0.22 [- 0.36/- 0.08] vs. βXa inhibitor - 0.24 [- 0.37/- 0.11]) and lipid metabolism (ApoA1: βIIa inhibitor 0.10 [0.01/0.18] vs. βXa inhibitor 0.12 [0.04/0.20]) compared to VKA therapy. CONCLUSION This study provides the first evidence for differential, non-conventional associations of oral anticoagulants on cardiac function and lipid metabolism in humans. The potentially beneficial effect of DOACs in the highly vulnerable population of HF individuals needs to be further elucidated and may have implications for individually tailored anticoagulation therapy.
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Myocardial Performance in Elite Athletes: The Role of Homocysteine, Iron, and Lipids.
Duyuler, S
Medical science monitor : international medical journal of experimental and clinical research. 2019;:1194-1203
Abstract
BACKGROUND The myocardial performance index (MPI) is a comprehensive measure of global systolic and diastolic function of the ventricle, and it has an inverse correlation with maximal oxygen consumption. In this study, the potential association between left ventricle MPI and biochemical biomarkers (including iron, homocysteine, and lipids) in elite athletes was investigated. MATERIAL AND METHODS This cross-sectional observational study consisted of 80 young male elite soccer and basketball players (age: 18-34 years) examined for a seasonal medical check-up. Cardiological examinations and transthoracic echocardiography of these athletes were performed and blood samples were analyzed according to standard laboratory protocols. Tissue Doppler recording was acquired from the mitral annulus using apical 4-chamber view and then the tissue Doppler-derived MPI was computed. RESULTS Athletes were separated into 2 groups based on MPI values (MPI ≤0.40 and MPI >0.40), and baseline demographic, clinical, and biochemical variables of the study participants were compared between these 2 groups. Serum triglyceride, high-density lipoprotein, total cholesterol, homocysteine levels, and iron parameters did not significantly differ between groups, while low-density lipoprotein level was significantly lower in the MPI ≤0.40 group (103.8±26.0 mg/dl vs. 116.8±30.2 mg/dl; p=0.043). Correlation analysis and multivariate linear regression analysis demonstrated a significant association between low-density lipoprotein and MPI. CONCLUSIONS In this study, various biochemical markers were evaluated for possible association with left ventricle MPI as a surrogate of cardiac performance. Among these biomarkers, only low-density lipoprotein was significantly associated with MPI in elite athletes.
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Helicobacter pylori eradication increases the serum high density lipoprotein cholesterol level in the infected patients with chronic gastritis: A single-center observational study.
Iwai, N, Okuda, T, Oka, K, Hara, T, Inada, Y, Tsuji, T, Komaki, T, Inoue, K, Dohi, O, Konishi, H, et al
PloS one. 2019;(8):e0221349
Abstract
BACKGROUND Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis. METHODS One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy. RESULTS The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased. CONCLUSIONS This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy.
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Association of High-Intensity Binge Drinking With Lipid and Liver Function Enzyme Levels.
Rosoff, DB, Charlet, K, Jung, J, Lee, J, Muench, C, Luo, A, Longley, M, Mauro, KL, Lohoff, FW
JAMA network open. 2019;(6):e195844
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Abstract
IMPORTANCE The prevalence of high-intensity binge drinking (HIBD), defined as consuming 2 or more times the binge threshold defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is rapidly increasing in the United States. While the relationship between alcohol consumption and lipid and liver function enzyme (LFT) biomarkers has been previously examined, the associations of HIBD with those biomarkers remain unknown. OBJECTIVE To examine associations of HIBD with lipid and LFT levels in a cross-sectional sample enriched with participants who engage in HIBD. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study using data from the NIAAA clinical sample collected from March 3, 2005, to August 21, 2017, with participants recruited for either the NIAAA screening protocols or inpatient alcohol treatment program. For this study, participants were stratified by self-reported alcohol consumption into 4 sex-specific binge levels: nonbinge and 1, 2, and 3 or more times the binge threshold (levels I, II, and III). Multivariable analyses examined the odds of clinically high levels of lipids and LFTs across binge levels. Analyses were performed from December 3, 2018, to January 30, 2019. MAIN OUTCOMES AND MEASURES Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. RESULTS A total of 2065 participants underwent protocol screening; 1519 with data available on alcohol consumption, body mass index, lipid levels, and LFT levels were included in the final analyses. Mean (SD) age was 39.7 (12.1) years; mean (SD) body mass index was 26.6 (5.1); 978 (64.4%) were male; 718 (47.3%) were white; and 578 (31.1%) consumed alcohol at the nonbinge level, 321 (21.2%) at level I, 239 (15.7%) at level II, and 318 (25.1%) at level III. High-intensity binge drinking was associated with 2- to 8-fold increased odds for clinically high levels of HDL-C, total cholesterol, triglycerides, and all LFTs (eg, for HDL-C: level III odds ratio [OR], 8.65; 95% CI, 4.75-15.77 and for γ-glutamyltransferase: level III OR, 8.21; 95% CI, 5.90-11.43). Increased HIBD frequency (days consuming at levels II and III) was associated with increased odds for clinically high levels of HDL-C, total cholesterol, and all LFTs (per unit increase in days consuming at the respective binge level) (eg, for HDL-C: level II OR, 1.025; 95% CI, 1.014-1.036 and level III OR, 1.033; 95% CI, 1.019-1.047 and for γ-glutamyltransferase: level II OR, 1.028; 95% CI, 1.019-1.037 and level III OR, 1.033; 95% CI, 1.019-1.047). CONCLUSIONS AND RELEVANCE High-impact binge drinking was significantly associated with increased odds for clinically high levels of lipids and LFTs. Given that HIBD is increasingly common among US adults, targeted interventions aimed at reducing HIBD may have important health benefits.
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Evidence from 3-month-old infants shows that a combination of postnatal feeding and exposures in utero shape lipid metabolism.
Furse, S, Snowden, SG, Olga, L, Prentice, P, Ong, KK, Hughes, IA, Acerini, CL, Dunger, DB, Koulman, A
Scientific reports. 2019;(1):14321
Abstract
We tested the hypothesis that both postnatal feeding and conditions in utero affect lipid metabolism in infants. Infants who experienced restrictive growth conditions in utero and others exposed to maternal hyperglycaemia were compared to a control group with respect to feeding mode. Dried blood spots were collected from a pilot subset of infant participants of the Cambridge Baby Growth Study at 3mo. Groups: (a) a normal gestation (control, n = 40), (b) small for gestational age (SGA, n = 34) and (c) whose mothers developed hyperglycaemia (n = 59). These groups were further stratified by feeding mode; breastfed, formula-fed or received a mixed intake. Their phospholipid, glyceride and sterol fractions were profiled using direct infusion mass spectrometry. Statistical tests were used to identify molecular species that indicated differences in lipid metabolism. The abundance of several phospholipids identified by multivariate analysis, PC(34:1), PC(34:2) and PC-O(34:1), was 30-100% higher across all experimental groups. SM(39:1) was around half as abundant in in utero groups among breastfed infants only. The evidence from this pilot study shows that phospholipid metabolism is modulated by both conditions in utero and postnatal feeding in a cohort of 133 Caucasian infants, three months post partum.
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Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.
Talbot, D, Delaney, JAC, Sandfort, V, Herrington, DM, McClelland, RL
Pharmacoepidemiology and drug safety. 2018;(4):365-372
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PURPOSE Estimating how much of the impact of statins on coronary heart diseases (CHD), cardiovascular disease (CVD), and mortality risk is attributable to their effect on low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides. METHODS A semi-parametric g-formula estimator together with data from the Multi-Ethnic Study of Atherosclerosis (a prospective multi-center cohort study) was utilized to perform a mediation analysis. A total of 5280 participants, men and women of various race/ethnicities from multiple sites across the United States, were considered in the current study. RESULTS The adherence adjusted total relative risk reduction (RRR) estimate (95% confidence interval) of statins on CHD was 14% (-16%, 37%), and the indirect component through LDL was 23% (-4%, 58%). For CVD, the total RRR was 23% (2%, 40%), and the indirect component through LDL was 5% (-13%, 25%). The total RRR of mortality was 18% (-1%, 35%), and the indirect component through LDL was -4% (-17%, 12%). The estimated indirect components through HDL and triglycerides were close to zero with narrow confidence intervals for all 3 outcomes. CONCLUSIONS The estimated effect of statins on mortality, CVD, and CHD appeared to be independent of their estimated effect on HDL and triglycerides. Our study provides evidence that the preventive effect of statins on CHD could be attributed in large part to their effect on LDL. Our g-formula estimator is a promising approach to elucidate pathways, even if it is hard to make firm conclusions for the LDL pathway on mortality and CVD.
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Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients.
Restrepo, JF, Del Rincon, I, Molina, E, Battafarano, DF, Escalante, A
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 2017;(3):144-148
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Abstract
BACKGROUND/PURPOSE We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.