ABSTRACT
BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity. There can be variation in the degree of weight reduction following bariatric surgery. It is unknown whether single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor locus (GRL) affect postoperative weight loss and metabolic outcomes. MATERIALS/METHODS: We studied the association between selected candidate SNPs and postoperative weight loss and metabolic outcomes in patients with severe obesity undergoing bariatric surgery. The polymorphisms rs41423247 (Bcl1), rs56149945 (N363S) and rs6189/rs6190 (ER22/23EK) were analysed. RESULTS: The 139 participants included 95 women (68.3%) and had a median (interquartile range) age of 53.0 (46.0-60.0) years and mean (SD) weight of 140.8 (28.8) kg and body mass index of 50.3 (8.6) kg/m2. At baseline, 59 patients had type 2 diabetes (T2D), 60 had hypertension and 35 had obstructive sleep apnoea syndrome treated with continuous positive airway pressure (CPAP). 84 patients (60.4%) underwent gastric bypass and 55 (39.6%) underwent sleeve gastrectomy. There were no significant differences in weight loss, glycated haemoglobin (HbA1c) or lipid profile categorized by genotype status, sex or median age. There was significant weight reduction after bariatric surgery with a postoperative BMI of 34.1 (6.8) kg/m2 at 24 months (p < 0.001). CONCLUSION: While GRL polymorphisms with a known deleterious effect on adipose tissue mass and function may have a small, additive effect on the prevalence of obesity and related metabolic disorders in the population, we suggest that the relatively weak biological influence of these SNPs is readily overcome by bariatric surgery.
Subject(s)
Bariatric Surgery , Polymorphism, Single Nucleotide , Receptors, Glucocorticoid , Weight Loss , Humans , Female , Middle Aged , Male , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Weight Loss/genetics , Prospective Studies , Treatment Outcome , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/surgery , Obesity, Morbid/surgery , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , AdultABSTRACT
BACKGROUND: Obesity is a risk factor for hyperuricemia and gout, while weight reduction can reduce urate levels. The aim of this study was to examine the effect of bariatric surgery on longitudinal serum urate levels. METHODS: We performed a retrospective observational study of 283 patients who had undergone bariatric surgery [237 (83.7%) gastric bypass, 34 (12.0%) sleeve gastrectomy and 12 (4.2%) gastric banding] and were followed up for 2 years. The results shown represent mean (standard deviation). RESULTS: Bariatric surgery was associated with significant reduction in serum urate from baseline level of 0.343 (0.086) mmol/L to 0.296 (0.076) mmol/L (p < 0.001) at 12 months and 0.286 (0.073) mmol/L (p < 0.001) at 24 months, including in men and women, and in patients with or without diabetes. Patients with elevated urate levels at baseline, who comprised 27.2% of the total cohort, achieved reduction in levels by 4 months. CONCLUSION: Bariatric surgery leads to significant reduction in serum urate levels at 12 and 24 months. This could reduce incidence of gout and need for prophylactic medication(s).
Subject(s)
Bariatric Surgery , Gastric Bypass , Gout , Obesity, Morbid , Male , Humans , Female , Uric Acid , Obesity, Morbid/surgery , Obesity/complications , Obesity/surgery , Bariatric Surgery/methods , Gastric Bypass/methods , Retrospective Studies , Gastrectomy/methods , Treatment OutcomeABSTRACT
BACKGROUND: There is a marked increase in the global prevalence of obesity over the last decades with an estimated 1.9 billion adults living with overweight or obesity. This is associated with a sharp rise in prevalence of cardiorenal metabolic diseases such as type 2 diabetes mellitus, chronic kidney disease, and heart failure. With recent evidence of the efficacy of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal protection and weight reduction, it is reasonable to investigate common causative pathways for cardiorenal metabolic diseases. SUMMARY: Central obesity is a common condition with 41.5% prevalence worldwide. It is associated with adverse outcomes even in people with a normal body mass index. Central obesity develops when the personal fat threshold for expansion in the subcutaneous adipose tissue exceeds a certain level. Multiple factors such as age, gender, genetics, and hormones may play a role in determining personal susceptibility to central obesity. Cardiorenal metabolic diseases usually cluster in certain populations - commonly in people with central obesity - and cause a substantial burden on health services and increase the risk of all-cause mortality. In this review, we investigate the pathophysiological pathways between central obesity and cardiorenal metabolic diseases. These pathways include activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, inflammation and oxidative stress, haemodynamic impairment, insulin resistance, and endothelial dysfunction. KEY MESSAGE: Central obesity has a pivotal role in the development of cardiorenal metabolic diseases and should be targeted with population-based approaches, such as dietary and lifestyle interventions, as well as the development of pharmacotherapy to reduce the burden of cardiorenal metabolic diseases.
Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Adult , Humans , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Obesity/complications , Obesity/epidemiology , Obesity/metabolism , Renin-Angiotensin System , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiologyABSTRACT
AIM: Whilst bariatric surgery is the most effective treatment for severe obesity, the aim of this study was to evaluate whether postoperative weight loss is similar in patients with or without metabolic syndrome. METHODS: We performed a 5-year observational retrospective comparative cohort analysis of bariatric surgery in 333 patients (72% women) without (Group A, n = 133) or with (Group B, n = 200) metabolic syndrome at baseline. RESULTS: Overall mean (SD) baseline body mass index was 51.7 (7.5) with no significant difference between groups. Overall mean percent total weight loss (%TWL) was 31.9% by 24 months after surgery. Although %TWL was greater in Group A (34.9%) than in Group B (30.2%, p = 0.006) at 24 months, there were no significant differences between groups subsequently up to 60 months of follow-up. Systolic and diastolic blood pressures and lipid profiles improved in both groups. In patients with metabolic syndrome at baseline, mean HbA1c reduced by 36.4% at 12 months and was sustained over the study period. CONCLUSIONS: We report that bariatric surgery results in comparable long-term weight loss in patients with or without metabolic syndrome alongside expected improvements in metabolic comorbidities.
ABSTRACT
BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. METHODS: We performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FINDINGS: Bariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. CONCLUSIONS: Bariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.
Subject(s)
Bariatric Surgery , Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/surgery , Non-alcoholic Fatty Liver Disease/epidemiology , Retrospective Studies , Glycated Hemoglobin , Longitudinal Studies , Bariatric Surgery/methods , Obesity, Morbid/complications , Obesity, Morbid/surgery , Alanine Transaminase , Gastrectomy/methods , Weight Loss/physiology , Cholesterol , Treatment OutcomeABSTRACT
Bariatric surgery improves dyslipidaemia and reduces body weight, but it remains unclear how bariatric surgery modulates gene expression in fat cells to influence the proprotein convertase subtilisin/kexin type 9 (PCSK-9) and low-density lipoprotein receptor (LDLR) gene expression. The expression of the PCSK9/LDLR/tumor necrosis factor-alpha (TNFα) gene in adipose tissue was measured in two groups of Zucker Diabetic Sprague Dawley (ZDSD) rats after Roux-en-Y gastric bypass (RYGB) surgery or 'SHAM' operation. There was lower PCSK9 (p = 0.02) and higher LDLR gene expression (p = 0.02) in adipose tissue in rats after RYGB. Weight change did not correlate with PCSK9 gene expression (r = -0.5, p = 0.08) or TNFα gene expression (r = -0.4, p = 0.1). TNFα gene expression was positively correlated with PCSK9 gene expression (r = 0.7, p = 0.001) but not correlated with LDLR expression (r = -0.3, p = 0.3). Circulating triglyceride levels were lower in RYGB compared to the SHAM group (1.1 (0.8-1.4) vs. 1.5 (1.0-4.2), p = 0.038) mmol/L with no difference in cholesterol levels. LDLR gene expression was increased post-bariatric surgery with the potential to reduce the number of circulating LDL particles. PCSK9 gene expression and TNFα gene expression were positively correlated after RYGB in ZDSD rats, suggesting that the modulation of pro-inflammatory pathways in adipose tissue after RYGB may partly relate to PCSK9 and LDLR gene expression.
Subject(s)
Bariatric Surgery , Diabetes Mellitus, Experimental , Animals , Rats , Adipose Tissue/metabolism , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/surgery , Gene Expression , Inflammation/genetics , Obesity/genetics , Obesity/surgery , Proprotein Convertase 9/genetics , Proprotein Convertases/genetics , Rats, Sprague-Dawley , Rats, Zucker , Receptors, LDL/genetics , Receptors, LDL/metabolism , Serine Endopeptidases/metabolism , Subtilisin/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Bariatric surgery in people with obesity can lead to long-term remission of type 2 diabetes mellitus (T2DM) and a reduction in the incidence of macrovascular complications. The impact of bariatric surgery on microvascular complications is less clear. In this narrative review, we sought to evaluate the effect of bariatric surgery on microvascular complications in patients with and without diabetes. The risk of developing microvascular complications is increased in people with obesity, and this is amplified in those with T2DM. The impact of metabolic surgery on microvascular complications is limited to a subgroup analysis of studies or statistical modeling to predict the glycemia-independent effect of bariatric surgery. While bariatric surgery halts the progression of retinopathy in those with minimal retinopathy, it may worsen in those with advanced retinopathy. Bariatric surgery improves proteinuria and major renal outcomes, regardless of the severity of renal impairment. Bariatric surgery in patients with obesity with or without diabetes is associated with an improvement in neuropathic symptoms and regeneration of small nerve fibers. In conclusion, bariatric surgery is associated with an improvement in microvascular complications. Further studies are needed to elucidate the underlying mechanisms for the favorable effect of bariatric surgery on microvascular outcomes.
Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Retinal Diseases , Humans , Diabetes Mellitus, Type 2/complications , Obesity/complications , Bariatric Surgery/adverse effects , Retinal Diseases/complications , Postoperative Complications/etiologyABSTRACT
Background: Obesity poses significant challenges to healthcare globally, particularly through its bi-directional relationship with co-morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods: A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings: Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity-related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion: Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi-faceted actions on major outcomes.
ABSTRACT
Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens. Yet, COVID-19 vaccine and booster uptake remain sluggish due to the mistaken beliefs that children have low rates of severe COVID-19 illness as well as rare but severe complications from COVID-19 vaccine are common. In this study we examined composite sAEFI reported in association with COVID-19 vaccines in the United States (US) amongst 5-17-year-old children, to ascertain the composite reported risk associated with vaccination. Between December 13, 2020, and April 13, 2022, a total of 467,890,599 COVID-19 vaccine doses were administered to individuals aged 5-65 years in the US, of which 180 million people received at least 2 doses. In association with these, a total of 177,679 AEFI were reported to the Vaccine Adverse Event reporting System (VAERS) of which 31,797 (17.9%) were serious. The rates of ED visits per 100,000 recipients were 2.56 (95% CI: 2.70-3.47) amongst 5-11-year-olds, 18.25 (17.57-18.95) amongst 12-17-year-olds and 33.74 (33.36-34.13) amongst 18-65-year olds; hospitalizations were 1.07 (95% CI 0.87-1.32) per 100,000 in 5-11-year-olds, 6.83 (6.42-7.26) in 12-17-year olds and 8.15 (7.96-8.35) in 18-65 years; life-threatening events were 0.14 (95% CI: 0.08-0.25) per 100,000 in 5-11-year olds, 1.22 (1.05-1.41) in 12-17-year-olds and 2.96 (2.85-3.08) in 18-65 year olds; and death 0.03 (95% CI 0.01-0.10) per 100,000 in 5-11 year olds, 0.08 (0.05-0.14) amongst 12-17-year olds and 0.76 (0.71-0.82) in 18-65 years age group. The results of our study from national population surveillance data demonstrate rates of reported serious AEFIs amongst 5-17-year-olds which appear to be significantly lower than in 18-65-year-olds. These low risks must be taken into account in overall recommendation of COVID-19 vaccination amongst children.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Middle Aged , Young Adult , Adverse Drug Reaction Reporting Systems , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Immunization/adverse effects , United States/epidemiology , Vaccination/adverse effectsSubject(s)
Body-Weight Trajectory , Hyperthyroidism , Humans , Prospective Studies , Weight Gain , Body WeightABSTRACT
Weight loss of 5%-10% is advised in medical weight management (MWM) programmes prior to bariatric surgery but it remains to be established whether it influences postoperative weight loss outcomes. We studied postoperative percent total weight loss (%TWL) in 168 patients categorized by preoperative referral weight loss <5% or ≥5% in a UK NHS bariatric centre. Eighty-six (51.2%) patients achieved sustained referral weight loss <5% (Group A) and 82 (48.8%) ≥5% (Group B). Overall postoperative %TWL in Group A compared with Group B was 30.0% versus 28.3% (p = .30) at 12 months and 32.5% versus 29.6% (p = .20) at 24 months. There were no significant differences in postoperative %TWL at 12 and 24 months when categorized by procedure (gastric bypass, n = 106; or sleeve gastrectomy, n = 62), age or sex. Preoperative weight loss during intensive specialist MWM did not influence postoperative weight loss up to 24 months with gastric bypass or sleeve gastrectomy.
Subject(s)
Bariatric Surgery , Gastric Bypass , Laparoscopy , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Retrospective Studies , Treatment Outcome , Gastric Bypass/methods , Weight Loss , Gastrectomy/adverse effects , Gastrectomy/methods , Laparoscopy/methodsABSTRACT
Objective: To analyze rates of reported severe adverse events after immunization (sAEFI) attributed to SARS-CoV-2 vaccines in the United States (US) using safety surveillance data. Methods: Observational study of sAEFI reported to the vaccine adverse events reporting system (VAERS) between December 13, 2020, to December 13, 2021, and attributed to SARS-CoV-2 vaccination programs across all US states and territories. All sAEFI in conjunction with mRNA (BNT-162b2 or mRNA-1273) or adenovector (Ad26.COV2.S) vaccines were included. The 28-day crude cumulative rates for reported emergency department (ED) visits and sAEFI viz. hospitalizations, life-threatening events and deaths following SARS-CoV-2 vaccination were calculated. Incidence rate ratios (IRRs) of reported sAEFI were compared between mRNA and adenovector vaccines using generalized Poisson regression models. Results: During the study period, 485 million SARS-CoV-2 vaccines doses were administered nationwide, and 88,626 sAEFI reported in VAERS. The 28-day crude cumulative reporting rates per 100,000 doses were 14.97 (95% confidence interval, 14.86-18.38) for ED visits, 5.32 (5.26-5.39) for hospitalizations, 1.72 (1.68-1.76) for life-threatening events, and 1.08 (1.05-1.11) for deaths. Females had two-fold rates for any reported AEFI compared to males, but lower adjusted IRRs for sAEFI. Cumulative rates per dose for reported sAEFI attributed to adenovector vaccine were 2-3-fold higher, and adjusted IRRs 1.5-fold higher than mRNA vaccines. Conclusions: Overall cumulative rates for reported sAEFI following SARS-CoV-2 vaccination in the US over 1 year were very low; single-dose adenovector vaccine had 1.5-fold higher adjusted rates for reported sAEFI, which may however equate with multiple-doses mRNA vaccine regimens. These data indicate absence of high risks of sAEFI following SARS-CoV-2 vaccines and support safety equipoise between mRNA and adenovector vaccines. Public health messaging of these data is critical to overcome heuristic biases. Furthermore, these data may support ongoing adenovector vaccine use, especially in low- and middle-income countries due to affordability, logistical and cold chain challenges.
Subject(s)
COVID-19 , Vaccines , Male , Female , United States/epidemiology , Humans , COVID-19 Vaccines/adverse effects , Adverse Drug Reaction Reporting Systems , Ad26COVS1 , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , RNA, Messenger , mRNA VaccinesABSTRACT
Background: The 2015 American Thyroid Association (ATA) Guidelines recommend the following size cut-offs based on sonographic appearances for subjecting nodules to fine-needle aspiration (FNA) biopsy: low risk: 15 mm and intermediate risk and high risk: 10 mm. Objective: We conducted a 'real-world' study evaluating the diagnostic performance of the ATA cut-offs against increased thresholds, in the interest of safely limiting FNAs. Methods: We performed a retrospective analysis of prospectively collected data on 604 nodules which were sonographically risk-stratified as per the ATA Guidelines and subsequently subjected to ultrasound-guided FNA. Nodules were cytologically stratified into 'benign' (Bethesda class 2) and 'non-benign' (Bethesda classes 3-6). We obtained the negative predictive value (NPV), accuracy, FNAs that could be spared, missed 'non-benign' cytologies and missed carcinomas on histology, according to the ATA cut-offs compared to higher cut-offs. Results: In low-risk nodules, the high performance of NPV (≈91%) is unaffected by increasing the cut-off to 25 mm, and accuracy improves by 39.4%; 46.8% of FNAs could be spared at the expense of few missed B3-B6 cytologies (7.9%) and no missed carcinomas. In intermediate-risk nodules, a 15 mm cut-off increases the NPV by 11.3% and accuracy by 40.7%. The spared FNAs approach 50%, while B3-B6 cytologies are minimal, with no missed carcinomas. In high-risk nodules, low NPV (<35%) and accuracy (<46%) were obtained regardless of cut-off. Moreover, the spared FNAs achieved at higher cut-offs involved numerous missed 'non-benign' cytologies and carcinomas. Conclusion: It would be clinically safe to increase the ATA cut-offs for FNA in low-risk nodules to 25 mm and in intermediate-risk nodules to 15 mm.
Subject(s)
Bariatric Surgery , Neural Tube Defects , Dietary Supplements , Female , Folic Acid/therapeutic use , Humans , Micronutrients , PregnancyABSTRACT
Bardet-Biedl syndrome (BBS) is a rare genetic condition, characterized by ciliary protein dysfunction, leading to multi-organ damage. People with BBS can develop early-onset severe obesity and associated problems including the metabolic syndrome, type 2 diabetes and coronary heart disease. Weight management can be challenging with the lack of effective medical therapies so far. We report a patient with BBS who underwent successful weight reduction through the use of glucagon-like peptide-1 receptor agonists.