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JACC. Advances May 2024It is not known whether the transition from obesity and severe obesity, as 2 different metabolic disease entities, affect flow-mediated and, thus, endothelium-dependent...
BACKGROUND
It is not known whether the transition from obesity and severe obesity, as 2 different metabolic disease entities, affect flow-mediated and, thus, endothelium-dependent epicardial vasodilation.
OBJECTIVES
The purpose of this study was to investigate the effect of obesity and severe obesity on flow-mediated epicardial vasomotion with positron emission tomography/computed tomography-determined longitudinal decrease in myocardial blood flow (MBF) from the base-to-apex direction of the left ventricle or gradient.
METHODS
N-ammonia positron emission tomography/computed tomography evaluated global MBF during pharmacologically induced hyperemia and at rest for assessment of coronary microvascular function. In addition, the Δ longitudinal MBF gradient (hyperemia minus rest) was determined. Patients were then grouped according to the body mass index (BMI) into normal weight (NW) (BMI 20.0-24.9 kg/m, n = 27), overweight (OW) (BMI 25.0-29.9 kg/m, n = 29), obesity (OB) (BMI 30.0-39.9 kg/m, n = 53), and severe obesity (morbid obesity: BMI ≥40 kg/m, n = 43).
RESULTS
Compared to NW, left ventricular Δ longitudinal MBF gradient progressively declined in OW and OB (0.04 ± 0.09 mL/g/min vs -0.11 ± 0.14 mL/g/min and -0.15 ± 0.11 mL/g/min; ≤ 0.001, respectively) but not significantly in SOB (-0.01 ± 0.11 mL/g/min, = 0.066). Regadenoson-induced global hyperemic MBF was lower in OB than in NW (1.88 ± 0.40 mL/g/min vs 2.35 ± 0.32 mL/g/min; ≤ 0.001), while comparable between NW and SOB (2.35 ± 0.32 mL/g/min vs 2.26 ± 0.40 mL/g/min; = 0.302). The BMI of the study population was associated with the Δ longitudinal MBF gradient in a U-turn fashion (r = 0.362, standard error of the estimate = 0.124; < 0.001).
CONCLUSIONS
Increased body weight associates with abnormalities in coronary circulatory function that advances from an impairment flow-mediated, epicardial vasodilation in overweight and obesity to coronary microvascular dysfunction in obesity, not observed in severe obesity. The U-turn of flow-mediated epicardial vasomotion outlines obesity and severe obesity to affect epicardial endothelial function differently.
PubMed: 38939628
DOI: 10.1016/j.jacadv.2024.100936 -
Alimentary Pharmacology & Therapeutics Jun 2024Glucagon-like peptide-1 receptor agonists (GLP-1RA) show anti-inflammatory properties.
BACKGROUND
Glucagon-like peptide-1 receptor agonists (GLP-1RA) show anti-inflammatory properties.
AIM
To evaluate their clinical impact on inflammatory bowel disease (IBD) outcomes.
METHODS
Retrospective cohort study utilising the TriNetX database comparing IBD-specific outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) and type 2 diabetes mellitus (T2DM) on GLP-1RA compared to oral hypoglycaemic agents. The primary outcome was hospitalisation requiring intravenous steroids and IBD-related surgery within 3 years. We performed 1:1 propensity score matching (PSM) for demographics, co-morbid conditions, BMI, laboratory values, HbA1c, and IBD medications including steroids.
RESULTS
We identified 1130 patients in the UC GLP-1RA cohort (mean age: 58.9 ± 11.6 years, 56.3% female, 70.2% White, 57.2% with obesity) and 1140 patients in the CD GLP-1RA cohort (mean age: 56.7 ± 11.5, 61.9% female, 73.6% White, 56.2% with obesity). After PSM, there was no difference in the risk of intravenous steroid use (aHR: 1.21, 95% CI: 0.92-1.59) but a lower risk of colectomy (aHR: 0.37, 95% CI: 0.14-0.97) between the UC GLP-1RA and control cohort. There was no difference in the risk of intravenous steroid use (aHR: 1.04, 95% CI: 0.80-1.34) but a lower risk of surgery (aHR: 0.55, 95% CI: 0.36-0.84) between the CD GLP-1RA and CD control cohort. There was no difference in the risk of oral steroid use or advanced therapy initiation in the UC and CD GLP-1RA than control cohorts.
CONCLUSIONS
We found an association between lower risk of IBD-related surgery and GLP-1RA use for T2DM in patients with UC or CD.
PubMed: 38938071
DOI: 10.1111/apt.18138 -
Scientific Reports Jun 2024A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM...
A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM after bariatric surgery. Inclusion criteria were subjects 18 to 65 years of age with morbid obesity undergoing bariatric surgery. All data were measured before and 6 and 12 months after surgery. The study included 104 subjects: women/men: 83/21; mean age 43.1 (SD 8.4) years; BMI: 38.8 kg/m (SD 3.8). Surgery with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) was performed in 84 (81%) and 20 (19%) subjects, respectively. From before to 6-12 months after surgery, procollagen type 1 N-terminal propeptid (P1NP) increased by 45.6 µg/L (95% CI 41.5-50.0, p < 0.001), and alkaline phosphatase (ALP) by 10 U/L (95% CI 7-14, p < 0.001). The increases were significantly larger after RYGB than after SG. The APOE- Ɛ3 allele was associated with low levels of BTM and high levels of leptin. There was an unfavourable increase in BTM after bariatric surgery. SG compared to RYGB and the presence of the APOE-Ɛ3 allele were associated with less unfavourable effects. The study emphasises the importance of optimal prophylactic interventions after bariatric surgery to prevent osteoporosis.
Topics: Humans; Female; Male; Adult; Middle Aged; Bone Remodeling; Biomarkers; Bariatric Surgery; Obesity, Morbid; Peptide Fragments; Procollagen; Gastrectomy; Gastric Bypass; Alkaline Phosphatase; Leptin; Aged; Adolescent
PubMed: 38937532
DOI: 10.1038/s41598-024-65952-y -
Langenbeck's Archives of Surgery Jun 2024Weight loss failure after bariatric surgery imposes great stress on patients and surgeons and great costs on healthcare systems. The literature review shows that weight...
BACKGROUND
Weight loss failure after bariatric surgery imposes great stress on patients and surgeons and great costs on healthcare systems. The literature review shows that weight loss failure is the most common cause of redo bariatric surgery. Therefore, identifying the predictors of weight loss failure in patients in the early stages can help bariatric surgeons. The present study aims to determine the association between primary weight loss and long-term weight loss outcomes.
METHODS
This retrospective cohort study was conducted on 329 patients undergoing OAGB who were followed for 60 months. For the prediction of short-term (24 months) and long-term (60 months) successful weight loss and weight regain, we used %TWL and BMI at any regular follow-ups.
RESULTS
In preoperative indices, age, sex, DLP, hypothyroidism, and HTN were not significant to predict successful short-term and long-term weight loss but %TWL at 12 months is a significant predictor of successful weight loss in short-term and long-term follow up. In the prediction of weight regain, preoperative indices (except BMI) were not significant but 12-month %TWL was a significant predictor.
CONCLUSIONS
This index can help surgeons find these patients early and provide helpful instructions to manage their issues more promptly to reach better weight loss outcomes.
Topics: Humans; Female; Male; Weight Loss; Retrospective Studies; Gastric Bypass; Adult; Middle Aged; Obesity, Morbid; Treatment Outcome; Body Mass Index; Time Factors; Cohort Studies; Anastomosis, Surgical
PubMed: 38937299
DOI: 10.1007/s00423-024-03371-3 -
Hepatology Communications Jul 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI)...
BACKGROUND
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI) with clinical outcomes in patients with MASLD.
METHODS
A retrospective cohort of 32,900 patients with MASLD, identified through the International Classification of Diseases-9 and 10 codes within the electronic health records of a large US-based health system, with a mean follow-up of 5.5 years (range: 1-15 y), was stratified into 6 BMI categories, <25, 25-<30, 30-<40, 40-<50, and ≥50 kg/m2.
RESULTS
The risk of liver decompensation and extrahepatic obesity-associated cancers had a J-shaped profile (both ps for linear and quadratic terms <0.05). Compared to patients with BMI 25-<30 kg/m2, the adjusted HRs (95% CIs) for liver decompensation of patients with BMI <25 and BMI ≥50 kg/m2 were 1.44 (1.17-1.77) and 2.27 (1.66-3.00), respectively. The corresponding figures for obesity-associated extrahepatic cancer were 1.15 (0.97-1.36) and 1.29 (1.00-1.76). There was an inverse association for BMI with liver transplantation and non-obesity-associated cancer (both ps for linear terms <0.05), but no association with HCC or all types of cancers combined. A similar J-shaped association between BMI and all-cause mortality was observed; adjusted HRs (95% CIs) for BMI <25 and ≥50 kg/m2 were 1.51 (1.32-1.72) and 3.24 (2.67-3.83), respectively, compared with BMI 25-<30 kg/m2 (both ps for linear and quadratic terms <0.001).
CONCLUSIONS
Patients with MASLD and very severe obesity (BMI ≥50 kg/m2) had the highest risk, exceeding that of patients with lean MASLD, for developing liver decompensation, obesity-associated extrahepatic cancers, or dying from any cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Body Mass Index; Obesity, Morbid; Adult; Aged; Risk Factors; Fatty Liver; United States; Liver Transplantation
PubMed: 38934706
DOI: 10.1097/HC9.0000000000000471 -
Medical Science Monitor : International... Jun 2024BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and...
BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.
Topics: Humans; Female; Male; Adult; Intercellular Signaling Peptides and Proteins; Inflammation; Case-Control Studies; Middle Aged; Adipose Tissue; Body Mass Index; Obesity, Morbid; Intra-Abdominal Fat; Subcutaneous Fat; Obesity
PubMed: 38932442
DOI: 10.12659/MSM.944462 -
Medicina (Kaunas, Lithuania) May 2024: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and...
: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. : We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild ( = 7), moderate ( = 19), or severe ( = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. : The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group ( = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( = 0.008 and = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( = 0.005 and < 0.0001, respectively). : In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
Topics: Humans; Interleukin-10; Obesity, Morbid; Female; Male; Adult; Middle Aged; Liver; Prospective Studies; Inflammation; Non-alcoholic Fatty Liver Disease
PubMed: 38929479
DOI: 10.3390/medicina60060862 -
Trials Jun 2024Morbid obesity is a complex chronic condition characterized by a body mass index of 40 kg/m or higher. The incidence of the condition is on the rise in developed...
Effects of whole-body vibration on body composition, microbiota, cardiometabolic markers, physical fitness, and quality of life after bariatric surgery: protocol for a randomized controlled trial.
BACKGROUND
Morbid obesity is a complex chronic condition characterized by a body mass index of 40 kg/m or higher. The incidence of the condition is on the rise in developed countries, and bariatric surgery has been proposed as a potential solution to address this trend. Nonetheless, bariatric surgery may also result in adverse effects, including a reduction in bone mineral density (BMD) and muscle mass, as well as an increased risk of fractures. The present study aims to elucidate the effects of bariatric surgery and whole-body vibration (WBV) training on body composition, microbiota, physical fitness, quality of life, and cardiometabolic markers.
METHODS
Twenty-eight participants (14 females), aged 18 to 50 years, will undergo sleeve gastrectomy surgery. They will be randomly allocated into a control group or a WBV training group. The WBV group will train three times per week with increasing intensities and duration ranging from 30 to 45 min over the 4-month training period. Measurements of body composition (dual-energy X-ray absorptiometry and peripheral quantitative computed tomography), physical fitness (muscular strength, agility, cardiorespiratory fitness, and balance), gait biomechanics, cardiometabolic markers, gut microbiota, quality of life, and physical activity levels will be collected at four different time points: (1) prior to the surgery, (2) 45 days post-surgery, (3) 6 months post-surgery, and (4) 18 months post-surgery.
DISCUSSION
Both groups are expected to experience improvements in most of the aforementioned variables. Nonetheless, we expect the WBV group to show larger improvements proving that the training is effective and safe.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05695599. Registered on January 25, 2023.
Topics: Humans; Vibration; Body Composition; Quality of Life; Female; Adult; Middle Aged; Male; Physical Fitness; Young Adult; Bariatric Surgery; Adolescent; Obesity, Morbid; Randomized Controlled Trials as Topic; Gastrointestinal Microbiome; Treatment Outcome; Biomarkers; Time Factors; Gastrectomy
PubMed: 38926901
DOI: 10.1186/s13063-024-08221-7 -
ESC Heart Failure Jun 2024Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this...
AIMS
Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75 years, both with and without co-morbidities.
METHODS AND RESULTS
In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48 h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis.
CONCLUSIONS
In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.
PubMed: 38923835
DOI: 10.1002/ehf2.14894 -
Metabolites Jun 2024Physical activity is effective for preventing and treating type 2 diabetes, but some individuals do not achieve metabolic benefits from exercise ("non-responders"). We...
Physical activity is effective for preventing and treating type 2 diabetes, but some individuals do not achieve metabolic benefits from exercise ("non-responders"). We investigated non-responders in terms of insulin sensitivity changes following a 12-week supervised strength and endurance exercise program. We used a hyperinsulinaemic euglycaemic clamp to measure insulin sensitivity among 26 men aged 40-65, categorizing them into non-responders or responders based on their insulin sensitivity change scores. The exercise regimen included VOmax, muscle strength, whole-body MRI scans, muscle and fat biopsies, and serum samples. mRNA sequencing was performed on biopsies and Olink proteomics on serum samples. Non-responders showed more visceral and intramuscular fat and signs of dyslipidaemia and low-grade inflammation at baseline and did not improve in insulin sensitivity following exercise, although they showed gains in VOmax and muscle strength. Impaired IL6-JAK-STAT3 signalling in non-responders was suggested by serum proteomics analysis, and a baseline serum proteomic machine learning (ML) algorithm predicted insulin sensitivity responses with high accuracy, validated across two independent exercise cohorts. The ML model identified 30 serum proteins that could forecast exercise-induced insulin sensitivity changes.
PubMed: 38921470
DOI: 10.3390/metabo14060335