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Aims: Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed. Methods and results: To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, P = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, P = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, P = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, P = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, P = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, P = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses. Conclusion: These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
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Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed. Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.
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Background: Among commonly performed bariatric surgeries, biliopancreatic diversion with duodenal switch (BPD-DS) provides greater weight loss than Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), with sustained metabolic improvements. However, the risk of long-term nutritional deficiencies due to the hypoabsorptive component of BPD-DS hinders its widespread use. Objective: The aim of the study was to examine nutritional status over 2 years after BPD-DS, RYGB or SG. Methods: Patients were recruited in the REMISSION trial (NCT02390973), a single-center, prospective study. Out of 215 patients, 73, 48 and 94, respectively, underwent BPD-DS, RYGB or SG. Weight loss, micronutrient serum levels (including iron, calcium, parathormone, vitamins A, B12 and D), and nutritional supplementation were assessed over 2 years. Patients were supplemented according to the type of surgery and individual micronutrient level evolution. Results: At baseline, BPD-DS patients were younger than SG patients (p = 0.0051) and RYGB patients had lower body mass index (p < 0.001). Groups had similar micronutrient levels before surgery, with vitamin D insufficiency as the most prevalent nutritional problem (SG: 38.3%, RYGB: 39.9%, BPD-DS: 54.8%, p = 0.08). BPD-DS patients showed lower levels of iron, calcium and vitamin A than SG patients at 24 months. Groups had similar levels of vitamin D at 24 months. Prevalence of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiency was similar among groups at 24 months. Rates of vitamin D insufficiency and iron deficiency were lower at 24 months than at baseline. Micronutrient intake was consistent with recommendations in groups post-surgery, but most BPD-DS patients took vitamin A and vitamin D supplement doses above initial recommendations. Conclusion: With appropriate medical and nutritional management, all surgeries led to similar rates of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiencies at 24 months. However, initial vitamin A and vitamin D supplementation recommendations for BPD-DS patients should be revised upwards.
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OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.
Subject(s)
Bariatric Surgery , Dietary Supplements , Humans , PharmacokineticsABSTRACT
Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 < p < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p Ë 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p Ë 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to -0.84 (small to large effects), p Ë 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype.
Subject(s)
Body Composition , Cardiometabolic Risk Factors , Cardiorespiratory Fitness , Resistance Training , Humans , Female , Middle Aged , Obesity, Metabolically Benign/blood , Obesity/therapy , Muscle Strength , Adiponectin/blood , Leptin/blood , Aged , Insulin Resistance , Case-Control Studies , Postmenopause , Cardiovascular Diseases/prevention & controlABSTRACT
BACKGROUND: Physical activity (PA) can play an important role in optimizing metabolic/bariatric surgery (MBS) outcomes. However, many MBS patients have difficulty increasing PA, necessitating the development of theory-driven counseling interventions. This study aimed to (1) assess the feasibility and acceptability of the TELEhealth BARIatric behavioral intervention (TELE-BariACTIV) trial protocol/methods and intervention, which was designed to increase moderate-to-vigorous intensity physical activity (MVPA) in adults awaiting MBS and (2) estimate the effect of the intervention on MVPA. METHODS: This trial used a repeated single-case experimental design. Twelve insufficiently active adults awaiting MBS received 6 weekly 45-min PA videoconferencing counseling sessions. Feasibility and acceptability data (i.e., refusal, recruitment, retention, attendance, and attrition rates) were tracked and collected via online surveys, and interviews. MVPA was assessed via accelerometry pre-, during, and post-intervention. RESULTS: Among the 24 patients referred to the research team; five declined to participate (refusal rate = 20.8%) and seven were ineligible or unreachable. The recruitment rate was 1.2 participants per month between 2021-09 and 2022-07. One participant withdrew during the baseline phase, and one after the intervention (retention rate = 83.3%). No participant dropouts occurred during the intervention and 98.6% of sessions were completed. Participants' anticipated and retrospective acceptability of the intervention was 3.2/4 (IQR, 0.5) and 3.0/4 (IQR, 0.2), respectively. There was a statistically significant increase in MVPA [Tau-U = 0.32(0.11; 0.51)] from pre- to post-intervention. CONCLUSION: Despite a low recruitment rate, which could be explained by circumstances (COVID-19 pandemic), results support feasibility, acceptability, and preliminary efficacy of the TELE-Bari-ACTIV intervention for increasing MVPA in patients awaiting MBS.
Subject(s)
Bariatric Surgery , Obesity, Morbid , Telemedicine , Adult , Humans , Feasibility Studies , Pandemics , Retrospective Studies , Obesity, Morbid/surgery , Exercise/psychologyABSTRACT
The Inuit population of Nunavik is faced with a significant rise in the prevalence of obesity [body mass index (BMI) ≥ 30 kg/m2], but the impact on cardiometabolic health is unclear. The aim of this study was to characterize adiposity phenotypes and explore their associations with cardiometabolic risk factors among Nunavimmiut men and women. We used data obtained from 1296 Inuit who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health survey. Collected information included demographics, anthropometric measurements including visceral fat level (VFL) measured using electrical bioimpedance, biomarkers, hemodynamics, medical history and medication list. Adjusted population-weighted linear regressions were conducted to assess associations between body fat distribution and cardiometabolic risk factors. The accuracy and cut-off points of anthropometric indices to detect cardiometabolic abnormalities was evaluated by area under the receiver operator characteristic curve (AUROC) and a maximum Youden index analysis. Among Nunavimmiut (mean age 38.8 years [95%CI: 38.4 to 39.3]), obesity was observed in 42.8% of women and 25.6% of men. Compared to men, women presented a higher prevalence of abdominal obesity (78.8% vs. 46.4% in men, p < 0.05) and elevated VFL (54.4% vs. 20.1% with an InBody level ≥ 13, p < 0.05). Indices of global fat distribution and abdominal adiposity including VFL provided poor to moderate ability to detect cardiometabolic abnormalities (AUROC between 0.64 and 0.79). This analysis revealed that despite a high prevalence of abdominal obesity, particularly among women, anthropometric measurements of adiposity are inconsistently associated cardio-metabolic risk factors in Inuit adults of Nunavik.
Subject(s)
Adiposity , Cardiovascular Diseases , Adult , Male , Humans , Female , Obesity, Abdominal/complications , Inuit , Obesity/epidemiology , Risk Factors , Body Mass Index , Cardiovascular Diseases/epidemiology , PhenotypeABSTRACT
BACKGROUND: A better understanding of adipose tissue (AT) dysfunction, which includes morphological and functional changes such as adipocyte hypertrophy as well as impaired adipogenesis, lipid storage/mobilization, endocrine and inflammatory responses, is needed in the context of obesity. One dimension of AT dysfunction, secretory adiposopathy, often assessed as a low plasma adiponectin (A)/leptin (L) ratio, is commonly observed in obesity. The aim of this study was to examine markers of AT development and metabolism in 67 women of varying age and adiposity (age: 40-62 years; body mass index, BMI: 17-41 kg/m2) according to levels of adiponectinemia, leptinemia or the plasma A/L ratio. METHODS: Body composition, regional AT distribution and circulating adipokines were determined. Lipolysis was measured from glycerol release in subcutaneous abdominal (SCABD) and omental (OME) adipocytes under basal, isoproterenol-, forskolin (FSK)- and dibutyryl-cyclic AMP (DcAMP)-stimulated conditions. Adipogenesis (C/EBP-α/ß/δ, PPAR-γ2 and SREBP-1c) and lipid metabolism (ß2-ARs, HSL, FABP4, LPL and GLUT4) gene expression (RT-qPCR) was assessed in both fat depots. Participants in the upper versus lower tertile of adiponectin, leptin or the A/L ratio were compared. RESULTS: Basal lipolysis was similar between groups. Women with a low plasma A/L ratio were characterized by higher adiposity and larger SCABD and OME adipocytes (p<0.01) compared to those with a high ratio. In OME adipocytes, women in the low adiponectinemia tertile showed higher isoproterenol-stimulated lipolysis (0.01
Subject(s)
Adiponectin , Leptin , Female , Humans , Adult , Middle Aged , Adiponectin/metabolism , Leptin/metabolism , Isoproterenol/metabolism , Adipose Tissue/metabolism , Obesity/metabolismABSTRACT
The aims of this study were to compare, between pregnant individuals with and without bariatric surgery: (1) eating behaviors, (2) intuitive eating components and, (3) attitudes towards weight gain. This retrospective study included data collected in healthy pregnant individuals with and without previous bariatric surgery who were recruited at the Centre Hospitalier Universitaire (CHU) de Québec-Université Laval. Pregnant individuals who underwent bariatric surgery (biliopancreatic bypass with duodenal switch [n = 14] or sleeve gastrectomy [n = 5]) were individually matched, for age (±0.4 years) and body mass index (BMI) (±0.3 kg/m2), with pregnant individuals who have not received bariatric surgery. In the second trimester, participants completed the Three Factor Eating Questionnaire (TFEQ) and the Intuitive Eating Scale 2 (IES-2). In the third trimester, participants completed the French version of the Pregnancy Weight Gain Attitude Scale assessing attitudes towards weight gain. Pregnant individuals who have had bariatric surgery had a higher score for flexible restraint and a lower score for situational susceptibility to disinhibition compared to individuals who have not had undergone bariatric surgery (2.89 ± 1.15 vs. 1.95 ± 1.31; p = 0.04 and 1.11 ± 1.29 vs. 2.79 ± 1.44, respectively; p < 0.001). Regarding intuitive eating, pregnant individuals who experienced bariatric surgery had a higher score for reliance on internal hunger and satiety cues and a lower one for unconditional permission to eat compared with those who had not experienced bariatric surgery (3.99 ± 0.81 vs. 3.30 ± 1.03; p = 0.02 and 3.28 ± 0.54 vs. 3.61 ± 0.68, respectively; p = 0.03). No difference in attitudes towards weight gain was observed between groups. Overall, pregnant individuals who had undergone bariatric surgery had different eating behaviors and intuitive eating components compared to pregnant individuals without bariatric surgery. These results need to be confirmed in further studies with larger sample sizes.
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BACKGROUND: Many patients achieve short-term type 2 diabetes (T2D) remission after bariatric surgery, but relapses are common. Diabetes outcomes after bariatric surgery vary across procedures and populations. T2D remission scores are simple clinical tools developed to predict remission after bariatric surgery. However, they have never been tested after Biliopancreatic diversion with duodenal switch (BPD-DS). OBJECTIVES: The aim of this study was to compare the predictive value of T2D remission scores and preoperative diabetes characteristics in predicting T2D remission after BPD-DS. SETTING: Quebec Heart and Lung Institute - Laval University. METHODS: We retrospectively identified 918 patients with preoperative T2D who had undergone BPD-DS. Retrospective chart review was performed and variables used to calculate predictive scores were captured. T2D status was assessed annually for up to 10 years postop. Predictive values for each score (DiarRem, Ad Diarem, and Diabetter) and single preoperative diabetes characteristics used to construct these algorithms were evaluated by area under receiver operating characteristic curves (AUC). RESULTS: Diabetter showed greater performance for prediction of durable diabetes remission than other algorithms with acceptable discriminative ability (AUC between .69 and .79), but was not superior to T2D duration as a single predictor (P = .24 and P = .18). At 10 years, T2D duration had a better discriminative ability for the prediction of T2D remission than all 3 predictive models (AUC = .85, P < .05). CONCLUSIONS: Better chances for T2D remission following BPD-DS are associated with a shorter duration or T2D before surgery. Duration of T2D alone offers an excellent predictive ability and is a convenient alternative to diabetes remission scores to estimate chances of long-term diabetes remission after BPD-DS.
Subject(s)
Biliopancreatic Diversion , Diabetes Mellitus, Type 2 , Duodenum , Humans , Diabetes Mellitus, Type 2/surgery , Biliopancreatic Diversion/methods , Female , Male , Retrospective Studies , Middle Aged , Duodenum/surgery , Adult , Remission Induction , Obesity, Morbid/surgery , Treatment Outcome , Predictive Value of Tests , Preoperative PeriodABSTRACT
Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with positron emission tomography were used to measure fatty acid metabolism in 40 men and women with normal or impaired glucose tolerance (NCT02808182), and single nuclei RNA-sequencing (snRNA-seq) to determine transcriptional dynamics of subcutaneous adipose tissue (AT) between individuals with AT hypertrophy vs. hyperplasia matched for sex, ethnicity, glucose-tolerance status, BMI, total and percent body fat, and waist circumference. Adipocyte size was associated with high postprandial total cardiac fatty acid uptake and higher visceral AT dietary fatty acid uptake, but lower lean tissue dietary fatty acid uptake. We found major shifts in cell transcriptomal dynamics with AT hypertrophy that were consistent with in vivo metabolic changes.
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BACKGROUND AND AIMS: RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases. METHODS: RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank. RESULTS: In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [-0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (-0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60). CONCLUSIONS: PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.
Subject(s)
Atherosclerosis , Brain Ischemia , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Pancreatitis , Stroke , Humans , Acute Disease , Coronary Artery Disease/genetics , Angiopoietin-Like Protein 3 , Antibodies , Apolipoproteins B/genetics , TriglyceridesABSTRACT
PURPOSE OF REVIEW: Many studies using metabolomics have tried to unravel the metabolic signature of obesity and understand the pathophysiology of this complex and heterogeneous disease. Circulating levels of the amino acid glutamate have been consistently associated with obesity and more specifically with measurements of abdominal fat accumulation. The purpose of this narrative review is to highlight recent studies documenting this association. RECENT FINDINGS: Circulating glutamate concentrations have been positively correlated with measurements of central fat accumulation such as waist circumference and visceral adipose tissue area. Moreover, elevated glutamate levels have been linked to a higher prevalence of type 2 diabetes, cardiovascular diseases and nonalcoholic fatty liver disease. The association with adiposity is detected in early life, and genetic predisposition does not appear as a major driver. Glutamate levels reflect in vivo synthesis rather than dietary intake. However, interventions generating metabolic improvements such as incretin receptor agonist treatment or dietary improvements may reduce plasma levels of this amino acid. SUMMARY: Recent findings confirm the consistent association between circulating glutamate and abdominal obesity and its cardiometabolic complications. The pathophysiological pathways underlying this phenomenon are still unclear. Furthermore, studies are needed to establish the usefulness of this analyte as a biomarker of abdominal obesity.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/epidemiology , Obesity, Abdominal/complications , Glutamic Acid , Obesity/complications , Adiposity/genetics , Amino Acids/metabolism , Waist Circumference , Intra-Abdominal Fat/metabolism , Body Mass Index , Risk FactorsABSTRACT
BACKGROUND AND AIM: Fatty Liver Index (FLI) is a simple clinical scoring system estimating non-alcoholic fatty liver disease (NAFLD). It is validated in European-descent and Asian populations, but not in sub-Saharan Africans. The aim of this study is to evaluate the validity of the FLI for predicting NAFLD in a population from Kenya. METHODS: Participants were recruited from a community-based study conducted in Kenya. NAFLD was diagnosed using hepatic ultrasonography. Clinical, anthropometrical, biochemical and lifestyle data were obtained. The accuracy and cut-off point of the FLI to detect NAFLD were evaluated by area under the receiver operator characteristic curve and the maximum Youden index analysis. RESULTS: A total of 640 participants (94 with NAFLD) were included. Mean age was 37.4 ± 0.4 years and 58.7% were women. Mean body mass index (BMI) was 22.3 ± 0.2 kg/m2 and waist circumference (WC) 79.1 ± 0.4 cm. A total of 15 (2.3%) participants were diagnosed with type 2 diabetes and 65 (10.2%) with obesity (BMI ≥ 30 kg/m2 ). AUROC of FLI for predicting NAFLD was 0.80 (95% CI 0.74-0.85), which was significantly higher compared to individual components gamma-glutamyl transferase and triglycerides (p < 0.05), but not compared to anthropometric parameters BMI (AUROC of 0.83, 95% CI 0.79-0.88) and WC (AUROC of 0.81, 95% CI 0.76-0.87). CONCLUSIONS: FLI is a simple valid scoring system to use in rural and urban Kenyan adults. However, this index might not be superior to BMI or WC to predict NAFLD, and those measurements might therefore be more appropriate in limited settings.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Adult , Humans , Female , Male , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Kenya/epidemiology , ROC Curve , Body Mass Index , Waist CircumferenceABSTRACT
PURPOSE: After metabolic and bariatric surgery (MBS), many patients have excess skin (ES), which can cause inconveniences. Identifying factors related to ES quantity and inconveniences is crucial to inform interventions. The aim of this study was to identify sociodemographic, physical, psychosocial, and behavioral factors associated with ES quantity and inconveniences. MATERIALS AND METHODS: A mixed-method study with a sequential explanatory design was conducted with 124 adults (92% women, Mage 46.5 ± 9.9 years, Mtime post-MBS 34.2 ± 27.6 months). During phase I, ES quantity (arms, abdomen, thighs) and inconveniences and sociodemographic, anthropometric, clinical, and behavioral outcomes were assessed. In phase II, 7 focus groups were performed with 37 participants from phase I. A triangulation protocol was completed to identify convergences, complementarities, and dissonances from quantitative and qualitative data. RESULTS: Quantitative data indicate only ES quantity on arms was associated with ES inconveniences on arms (r = .36, p < .01). Total ES quantity was associated with maximal body mass index (BMI) reached pre-MBS (r = .48, p < .05) and current BMI (r = .35, p < .05). Greater ES inconvenience was associated with higher social physique anxiety and age (R2 = .50, p < .01). Qualitative data were summarized into 4 themes: psychosocial experiences living with ES, physical ailments due to ES, essential support and unmet needs, and beliefs of ES quantity causes. CONCLUSION: Measured ES quantity is related to higher BMI, but not reported inconveniences. Greater self-reported ES quantity and inconveniences were associated with body image concerns.
Subject(s)
Bariatric Surgery , Obesity, Morbid , Adult , Humans , Female , Middle Aged , Male , Obesity, Morbid/surgery , Bariatric Surgery/methods , Body Image/psychology , Body Mass IndexABSTRACT
OBJECTIVE: To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. METHODS: Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. RESULTS: BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. CONCLUSIONS: BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.
Subject(s)
Biliopancreatic Diversion , Gastric Bypass , Gastrointestinal Hormones , Gastrointestinal Microbiome , Obesity, Morbid , Male , Rats , Animals , Rats, Wistar , Chromatography, Liquid , RNA, Ribosomal, 16S , Tandem Mass Spectrometry , Biliopancreatic Diversion/methods , Duodenum/surgery , Gastrectomy , Tyrosine , Obesity, Morbid/surgery , Gastric Bypass/methods , Retrospective StudiesABSTRACT
OBJECTIVE: To determine the rate of histology-proven Helicobacter pylori (HP) infection in patients undergoing bariatric surgery and to identify risk factors for HP infection. METHODS: In a retrospective analysis, patients who underwent bariatric surgery with gastric resection in a single hospital between January 2004 and January 2019 were analyzed. For each patient, a surgical specimen was submitted for anatomopathological examination and analyzed for gastritis or other anomalies. When gastritis was present, HP infection was confirmed by the identification of curvilinear bacilli in conventional histology or by specific immunohistochemical detection of HP antigen. RESULTS: A total of 6388 specimens were available for review (4365 women, 2023 men) with a mean age of 44.9 ± 11.2 years and a mean body mass index (BMI) of 49.3 ± 8.2 kg/m2. Histology-proven HP infection rate was 6.3% (n = 405). There was no significant difference in sex, BMI, and body weight between HP + and HP - patients. Logistic regressions identified age as a risk factor for HP infection in this population (OR 1.02, p < 0.0001, CI 95% 1.01-1.03 for every 1-year increase, OR 1.26, p < 0.0001, CI 95% 1.14-1.40 for every 10-year increase). CONCLUSIONS: The rate of histology-proven HP infection is low in patients with severe obesity who present for bariatric surgery and is associated with age.
Subject(s)
Bariatric Surgery , Gastritis , Helicobacter Infections , Helicobacter pylori , Obesity, Morbid , Male , Humans , Female , Adult , Middle Aged , Helicobacter Infections/complications , Obesity, Morbid/surgery , Retrospective Studies , Prevalence , Bariatric Surgery/adverse effects , Gastritis/complicationsABSTRACT
BACKGROUND: Epicardial adipose tissue (EAT) has garnered attention as a prognostic and risk stratification factor for cardiovascular disease. This study, via meta-analyses, evaluates the associations between EAT and cardiovascular outcomes stratified across imaging modalities, ethnic groups, and study protocols. METHODS: Medline and Embase databases were searched without date restriction on May 2022 for articles that examined EAT and cardiovascular outcomes. The inclusion criteria were (1) studies measuring EAT of adult patients at baseline and (2) reporting follow-up data on study outcomes of interest. The primary study outcome was major adverse cardiovascular events. Secondary study outcomes included cardiac death, myocardial infarction, coronary revascularization, and atrial fibrillation. RESULTS: Twenty-nine articles published between 2012 and 2022, comprising 19 709 patients, were included in our analysis. Increased EAT thickness and volume were associated with higher risks of cardiac death (odds ratio, 2.53 [95% CI, 1.17-5.44]; P=0.020; n=4), myocardial infarction (odds ratio, 2.63 [95% CI, 1.39-4.96]; P=0.003; n=5), coronary revascularization (odds ratio, 2.99 [95% CI, 1.64-5.44]; P<0.001; n=5), and atrial fibrillation (adjusted odds ratio, 4.04 [95% CI, 3.06-5.32]; P<0.001; n=3). For 1 unit increment in the continuous measure of EAT, computed tomography volumetric quantification (adjusted hazard ratio, 1.74 [95% CI, 1.42-2.13]; P<0.001) and echocardiographic thickness quantification (adjusted hazard ratio, 1.20 [95% CI, 1.09-1.32]; P<0.001) conferred an increased risk of major adverse cardiovascular events. CONCLUSIONS: The utility of EAT as an imaging biomarker for predicting and prognosticating cardiovascular disease is promising, with increased EAT thickness and volume being identified as independent predictors of major adverse cardiovascular events. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42022338075.
Subject(s)
Atrial Fibrillation , Myocardial Infarction , Adult , Humans , Pericardium/diagnostic imaging , Tomography, X-Ray Computed/methods , Echocardiography , Adipose Tissue/diagnostic imagingABSTRACT
The severity of the symptoms associated with COVID-19 is highly variable, and has been associated with circulating amino acids as a group of analytes in metabolomic studies. However, for each individual amino acid, there are discordant results among studies. The aims of the present study were: (i) to investigate the association between COVID-19-symptom severity and circulating amino-acid concentrations; and (ii) to assess the ability of circulating amino-acid levels to predict adverse outcomes (intensive-care-unit admission or hospital death). We studied a sample of 736 participants from the Biobanque Québécoise COVID-19. All participants tested positive for COVID-19, and the severity of symptoms was determined using the World-Health-Organization criteria. Circulating amino acids were measured by HPLC-MS/MS. We used logistic models to assess the association between circulating amino acids concentrations and the odds of presenting mild vs. severe or mild vs. moderate symptoms, as well as their accuracy in predicting adverse outcomes. Patients with severe COVID-19 symptoms were older on average, and they had a higher prevalence of obesity and type 2 diabetes. Out of 20 amino acids tested, 16 were significantly associated with disease severity, with phenylalanine (positively) and cysteine (inversely) showing the strongest associations. These associations remained significant after adjustment for age, sex and body mass index. Phenylalanine had a fair ability to predict the occurrence of adverse outcomes, similar to traditionally measured laboratory variables. A multivariate model including both circulating amino acids and clinical variables had a 90% accuracy at predicting adverse outcomes in this sample. In conclusion, patients presenting severe COVID-19 symptoms have an altered amino-acid profile, compared to those with mild or moderate symptoms.
ABSTRACT
Background: Lifestyle modifications have been recommended as an essential treatment approach for cardiovascular diseases. Recent studies have shown that eating frequency (EF) correlates with hypertension and related risk of organ damage. This study aimed to examine critical clinical implications to evaluate the association of EF with arterial stiffness parameters as an early marker of atherosclerosis manifestations. Methods: A cross-sectional descriptive study was performed on 658 participants of the PERSIAN Organizational Cohort study in Mashhad, aged 3070 years. Arterial stiffness was assessed by measurement markers of arteriosclerosis, including arterial age, augmentation index (AIx), augmentation pressure (AP), carotid-femoral pulse wave velocity (Cf-PWV), and central blood pressure. Differences in anthropometric indices, blood indices, and arterial stiffness parameters were evaluated across EF groups. Results: Our data demonstrate that EF was positively correlated with total daily energy intake, and favourable profiles of adiposity and blood lipids. Subjects with an increased EF, had significantly lower AIx, AP, Arterial Age and Central blood pressure (P for trend<0.001) as compared to Lowest EF and not significant with PWV (P for trend, 0.19). Arterial stiffness was also significantly lower in those with increased EF compared with subjects with low EF. By Linear regression analysis, after adjustment for Confounding factors, except PWV, EF showed the associations with all of the non-invasive arterial stiffness parameters. Conclusion: Increased EF is associated with a lower wave reflection and blood pressure in the central arteries.(AU)
Introducción: Las modificaciones del estilo de vida se han recomendado como un enfoque de tratamiento esencial para las enfermedades cardiovasculares. Estudios recientes han demostrado que la frecuencia de las comidas (EF) se correlaciona con la hipertensión y el riesgo relacionado de daño orgánico. Este estudio tenía como objetivo examinar las implicaciones clínicas críticas para evaluar la asociación de la EF con los parámetros de rigidez arterial como un marcador temprano de las manifestaciones de la aterosclerosis. Métodos: Se realizó un estudio descriptivo transversal en 658 participantes del estudio de cohorte organizativo PERSIAN en Mashhad, de entre 30 y 70 años de edad. La rigidez arterial se evaluó mediante la medición de marcadores de arteriosclerosis, incluyendo la edad arterial, el índice de aumento (AIx), la presión de aumento (AP), la velocidad de la onda del pulso carótido-femoral (Cf-PWV) y la presión arterial central. Se evaluaron las diferencias en los índices antropométricos, los índices sanguíneos y los parámetros de rigidez arterial en los grupos de EF. Resultados: Nuestros datos demuestran que la EF se correlacionó positivamente con la ingesta energética diaria total, los perfiles favorables de adiposidad y los lípidos sanguíneos. Los sujetos con una EF aumentada, tenían un AIx, una AP, una edad arterial y una presión arterial central significativamente menores (p de tendencia <0,001) en comparación con la EF más baja y no significativa con la PWV (p de tendencia, 0,19). La rigidez arterial también fue significativamente menor en los sujetos con una mayor FE en comparación con los sujetos con una FE baja. Mediante un análisis de regresión lineal, después de ajustar los factores de confusión, excepto la VOP, la frecuencia de las comidas se asoció con todos los parámetros de rigidez arterial no invasivos. Conclusiones: El aumento de la FE se asocia a una menor reflexión de la onda y a una menor presión arterial en las arterias...(AU)