What is the evidence regarding the safety of new obesity pharmacotherapies.

The use of gut-hormone receptors agonists as new therapeutic options for obesity and some of its related comorbidities, such as type 2 diabetes, has resulted in an unprecedented efficacy in the medical management of people living with obesity (PLWO). Appraisal of the safety of these drugs is of utmost importance considering the large number of PLWO, and the potentially long exposure to these pharmacotherapies. In this narrative review we summarize the evidence on the safety of liraglutide, semaglutide, and tirzepatide as derived from randomized clinical trials conducted in adults living with obesity. Additionally, the safety of these drugs is put into perspective with that of other drugs currently approved for the treatment of PLWO. Overall, the available data support a favorable efficacy versus safety balance for gut-hormone hormone receptor analogues in the treatment of these subjects. Nonetheless, it should be acknowledged that in the context of a chronic disease that has reached epidemic proportions, data from randomized clinical trials aimed primarily at proving the efficacy of these drugs may have been insufficient to unveil all the safety issues. Thus, continuous surveillance on the adverse effects of liraglutide, semaglutide, and tirzepatide is required as we use these drugs in a broader population than that represented in currently available clinical trials.

Weight-loss thresholds after bariatric surgery and cardiovascular outcomes: more is better.

BACKGROUND/OBJECTIVES: Whether the extent of weight loss (WL) modulates bariatric surgery (BS) cardiovascular benefits has scarcely been assessed. Several WL thresholds have been commonly used to classify BS patients as good or poor responders without a proven clinical relevance. We examined the relationship between the magnitude of WL after BS and post-surgery major adverse cardiovascular-event (MACE) incidence. We also compared the performance of three different insufficient weight-loss (IWL) criteria for their association with MACE. SUBJECTS AND METHODS: All individuals who underwent a primary Roux-en Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in our institution at least six years before data analysis (12/2020) were included in the study. Data on MACE were available in 1638 of 1700 participants (96.4%). Proportional-hazard Cox analyses were performed to ascertain the association between MACE, WL, and the three IWL criteria. IWL was defined as: <50% excess weight loss (<50% EWL), <20% total body-weight loss (<20% TBWL), and -1 standard deviation of alterable weight-loss percentage (<1 SD% AWL). RESULTS: During a mean follow-up of 10.2 ± 2.8 years, 86 participants experienced a first post-surgery MACE. Higher WL at one year (HR: 0.77 (95% CI: 0.61-0.98)) and 5 years (HR: 0.63 (95% CI: 0.42-0.92)) was related to a lower incidence of MACE. All short-term criteria for defining IWL were similarly associated with MACE, yet <1 SD% AWL identified more at-risk subjects. Five-year TBWL < 20% and 5-year <1 SD-AWL% were significantly associated with a higher risk for CV events. TBWL < 20% identified more subjects at risk. CONCLUSIONS: The extent of WL is closely related to long-term MACE incidence. Patients who lost -1SD% AWL at one year or <20% TBWL at five years may be considered poor responders.

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR.

Coronavirus disease 2019 (COVID-19) and obesity. Impact of obesity and its main comorbidities in the evolution of the disease.

The COVID-19 pandemic is posing a great challenge worldwide. Its rapid progression has caused thousands of deaths worldwide. Although multiple aspects remain to be clarified, some risk factors associated with a worse prognosis have been identified. These include obesity and some of its main complications, such as diabetes and high blood pressure. Furthermore, although the possible long-term complications and psychological effects that may appear in survivors of COVID-19 are not well known yet, there is a concern that those complications may be greater in obese patients. In this manuscript, we review some of the data published so far and the main points that remain to be elucidated are emphasized.

Genetic background influences weight-loss trajectories on the mid-term after bariatric surgery.

Bariatric surgery (BS) is a highly effective therapy for morbid obesity, yet with a wide inter-individual variability on weight-loss responses. To determine genetic influence on weight loss after BS we compared the within-pairs difference in maximum percentage excess weight loss (%EWL) and the within-pairs %EWL differences over a mean follow-up of 53.6 ± 36.4 months between 47 pairs of first-degree relatives and 47 genetically unrelated control pairs. Within-pairs maximum %EWL difference was similar between first-degree related pairs and control pairs (p = 0.100). Within-pairs %EWL difference increased through follow-up (p < 0.001). However, effect of time was different depending on genetic background (ptime*group = 0.001). Increased variability in mid-term weight response was present in unrelated pairs but not in first-degree pairs (p < 0.001 and p = 0.535, respectively). To assess shared environment influence, 16 married couples were identified and 16 unrelated and non-cohabiting matched pairs were also analyzed. In these analysis within-pairs difference in %EWL also increase over time (p = 0.025) but no group by time effect was observed (ptime×group = 0.177). In conclusion first-degree related participants showed closer weight trajectories after BS time than genetically unrelated subjects. Genetic background might partially explain the variability in mid-term weight-loss after BS.

Metabolic and Bariatric Surgery for Obesity.

Metabolic and bariatric surgery (MBS) leads to weight loss in obese individuals and reduces comorbidities such as type 2 diabetes. MBS is superior to medical therapy in reducing hyperglycemia in persons with type 2 diabetes, and has been associated with reduced mortality and incidences of cardiovascular events and cancer in obese individuals. New guidelines have been proposed for the use of MBS in persons with type 2 diabetes. We review the use of MBS as a treatment for obesity and obesity-related conditions and, based on recent evidence, propose that health care systems make the appropriate changes to increase accessibility for eligible patients.

Use of pulmonary function test demographic data to identify high-risk patients for lung cancer screening.

Lung Cancer is the primary cause of cancer-related death in the United States. We have recognized a need for novel methods of identification and consideration of enrollment into a lung cancer screening program for those at the highest risk of lung cancer. Our primary goal was to determine if pulmonary function test (PFT) demographic data would be useful in identifying patients for lung cancer screening. We retrospectively reviewed PFTs performed at Lahey Hospital & Medical Center (LHMC) January 2012 through January 2013 and found that of patients identified as high risk of lung cancer, 89% had passed through our PFT lab but had not yet been screened. Investigation into the barriers of lung cancer screening to better understand how to increase appropriate enrollment then followed. A total of 3098 PFTs were reviewed from January 2012 through January 2013 and 634 patients (20%) were identified as high risk for lung cancer.  Of 634 patients, 70 (11%) were already in the LHMC lung cancer screening program. The remaining 564 patients (89%) were not enrolled, and of these, it was found that 292 patients identified as high risk for lung cancer represented missed opportunities for screening. The remaining 272 patients were appropriately not screened with the three most common reasons being prior imaging with positive finding, lung cancer within five years, and provider discussed but scan not yet performed. Appropriate enrollment in a lung cancer screening program may be increased with the careful use of demographic data obtained from a PFT lab.

Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes Severity.

OBJECTIVE: To construct and validate a scoring system for evidence-based selection of bariatric and metabolic surgery procedures according to severity of type 2 diabetes (T2DM). BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) account for >95% of bariatric procedures in United States in patients with T2DM. To date, there is no validated model to guide procedure selection based on long-term glucose control in patients with T2DM. METHODS: A total of 659 patients with T2DM who underwent RYGB and SG at an academic center in the United States and had a minimum 5-year follow-up (2005-2011) were analyzed to generate the model. The validation dataset consisted of 241 patients from an academic center in Spain where similar criteria were applied. RESULTS: At median postoperative follow-up of 7 years (range 5-12), diabetes remission (HbA1C <6.5% off medications) was observed in 49% after RYGB and 28% after SG (P < 0.001). Four independent predictors of long-term remission including preoperative duration of T2DM (P < 0.0001), preoperative number of diabetes medications (P < 0.0001), insulin use (P = 0.002), and glycemic control (HbA1C < 7%) (P = 0.002) were used to develop the Individualized Metabolic Surgery (IMS) score using a nomogram. Patients were then categorized into 3 stages of diabetes severity. In mild T2DM (IMS score ≤25), both procedures significantly improved T2DM. In severe T2DM (IMS score >95), when clinical features suggest limited functional ß-cell reserve, both procedures had similarly low efficacy for diabetes remission. There was an intermediate group, however, in which RYGB was significantly more effective than SG, likely related to its more pronounced neurohormonal effects. Findings were externally validated and procedure recommendations for each severity stage were provided. CONCLUSIONS: This is the largest reported cohort (n = 900) with long-term postoperative glycemic follow-up, which, for the first time, categorizes T2DM into 3 validated severity stages for evidence-based procedure selection.

Remission of type 2 diabetes after Roux-en-Y gastric bypass or sleeve gastrectomy is associated with a distinct glycemic profile.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) have been associated with a high remission rate of type 2 diabetes mellitus (T2DM). However, whether such remission is associated with full restoration of postprandial glucose profile and/or the potentially nonrestored glycemic profile is associated with altered beta cell function, and relapse of T2DM over time is unknown. METHODS: Cross-sectional studies comparing (1) glucose and proinsulin/insulin response to a standardized liquid mixed meal (SLMM) challenge (n = 31), (2) glucose response in normal living conditions assessed using continuous glucose monitoring (CGM) (n = 16), and prospective observational study comparing (3) rates of relapse of T2DM after surgery (n = 232) in subjects with remission of T2DM ensuing RYGBP or SG. RESULTS: In RYGB individuals, SLMM elicited faster and sharper rise in plasma glucose compared with SG, with 88.2% and 42.9% of the study subjects presenting respectively a peak glucose more than 180 mg/dL (all, P < 0.05). During CGM, average percent time in hyperglycemic and hypoglycemic range was larger in RYGBP (respectively, 4.6% and 12.7%) compared with SG subjects (respectively, 0.4% and 3.2%; both P < 0.05). However, (1) no differences were found in fasting or stimulated proinsulin/insulin ratio, and (2) higher rates of T2DM relapse were observed after SG (hazard ratio: 2.339; P = 0.034). CONCLUSIONS: Remission of T2DM after RYGBP and SG is associated with distinct glycemic profiles. However, longer time spent in hyperglycemia and in hypoglycemia after RYGBP compared with SG is not associated with persistence of altered beta cell function or higher rates of relapse of T2DM over time.

Metabolic Surgery in Type 2 Diabetes: Roux-en-Y Gastric Bypass or Sleeve Gastrectomy as Procedure of Choice?

In recent years, a marked increase in the relative use of sleeve gastrectomy (SG) has occurred. However, long-term head-to-head comparison of the impact of this bariatric surgery (BS) procedure with the still considered "gold standard" Roux-en-Y gastric bypass (GBP) in subjects with type 2 diabetes mellitus (T2DM) is surprisingly low. The aim of this review manuscript is to appraise current evidence on the potential of GBP and SG as long-term therapeutic tool for subjects with T2DM. In our opinion, unfortunately, review of current literature does not allow to properly answer which of the two surgeries would be better as procedure of choice for subjects with T2DM. Arguably, the apparent superiority of GBP over SG could be overcome by the addition of a malabsortive component to SG in a staged approach restricted to those failing to achieve the desired metabolic outcomes. Nonetheless, whether this serves as basis for the election of SG as primary strategy for those with T2DM is questionable.

Typology of public outreach for biodiversity conservation projects in Spain.

Conservation education and outreach programs are a key approach to promote public understanding of the importance of biodiversity conservation. We reviewed 85 biodiversity conservation projects supported by the Spanish Ministry of Environment's Biodiversity Foundation. Through content analysis and descriptive statistics, we examined how the projects carried out communication, education, and public awareness and participation (CEPA) actions. We also used multivariate statistical analysis to develop a typology of 4 classes of biodiversity conservation projects on the basis of CEPA implementation. The classifications were delineated by purpose of CEPA, level of integration of CEPA actions, type of CEPA goals, main CEPA stakeholders, and aim of conservation. Our results confirm the existence of 2 key positions: CEPA has intrinsic value (i.e., they supposed the implementation of any CEPA action indirectly supported conservation) and CEPA is an instrument for achieving conservation goals. We also found that most CEPA actions addressed general audiences and school children, ignored minority groups and women, and did not include evaluation. The characteristics of the 4 types of projects and their frequency of implementation in the sample reflect the need for better integration of different types of actions (communication, education, and participation) and improved fostering of participation of multiple stakeholders in developing policy and implementing management strategies.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

Aims: We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. Material and methods: We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. Results: The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. Conclusions: In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes.

OBJECTIVE: Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored. RESEARCH DESIGN AND METHODS: We included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and 3-T MRI at baseline and 1-year post-BS. We assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEVs enriched for glial and astrocyte markers were determined by flow cytometry. RESULTS: Compared with control group, the obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the arcuate nucleus. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS. A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL 1 and 2 years after BS. CSF-lEVs did not differ among groups and were unrelated to WL trajectories. CONCLUSIONS: These findings suggest HI improvement after BS and may support a role for HI in modulating the WL response to these interventions.

GLP-1 and the long-term outcome of type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery in morbidly obese subjects.

OBJECTIVE: To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP). METHODS: Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition. RESULTS: Patients in G1 presented a lower area under the curve (AUC0-120) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC0-120 of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger ß-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups. CONCLUSIONS: Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that ß-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.

Diabetes remission following metabolic surgery: is GLP-1 the culprit?

The parallel occurrence of improved glucose tolerance and increased glucagon-like peptide 1 (GLP-1) response to meal intake following metabolic surgery (MS) demonstrated in several studies has led to the notion that GLP-1 is the culprit for the impressive rates of remission of type 2 diabetes mellitus (T2DM) following MS. In this article, we critically review current evidence supporting this view. Recent studies specifically designed to elucidate a causative role of GLP-1 in the antidiabetic effects of MS call into question GLP-1 as a key player for T2DM outcome following MS procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy in morbidly obese subjects. Whether GLP-1 plays a more prominent role in the remission of T2DM following MS in subjects with moderate obesity warrants further studies. Appraisal of the mechanisms involved in the amelioration of hyperglycemia following MS is a priority, as it could help in the battle against the current combined epidemics of obesity and T2DM.

Weight loss independently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery.

BACKGROUND: Despite obesity being closely associated with two common risk factors for albuminuria, namely type 2 diabetes mellitus (T2DM) and hypertension, information on the impact of weight loss on albumin excretion rate in morbidly obese (MO) subjects is scarce. OBJECTIVE: To evaluate the independent contribution of weight loss following bariatric surgery (BS) to the improvement of the albumin-to-creatinine ratio (ACR) in MO subjects with T2DM. SUBJECTS AND METHODS: Observational prospective study, including consecutive (n = 255) patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) of whom 37.6 % (n = 96) presented with T2DM. Stepwise logistic regression analysis was used to assess the contribution of T2DM-related, hypertension-related, and weight loss-related variables, and type of surgery to normalization of ACR (<30 mg/g) at 12 and 24 months follow-up. RESULTS: In T2DM subjects, baseline ACR was 85.7 ± 171 mg/g with ACR ≥ 30 mg/g being present in 45.7 % of the cohort. At 12 months, the ACR significantly decreased in T2DM subjects (42.2 ± 142.8 mg/g; p < 0.005) with no further reduction at 24 months after surgery (44.4 ± 227.7; p = 0.862). Among T2DM subjects with ACR ≥ 30 mg/g at baseline, the ACR became <30 mg/g in 58.5 % and 76.9 % at 12 and 24 months, respectively (p < 0.001 relative to baseline). Body mass index (BMI) change from baseline was the only independent predictor of ACR normalization at 12 months [Exp(B) 1.373, 95 % confidence interval 1.075-1.703; p < 0.05]. None of the evaluated variables appeared as an independent predictor of ACR normalization at 24 months. CONCLUSIONS: Our data suggest that, in MO subjects with T2DM, interventions aiming at slowing the progression of nephropathy should not only focus on optimization of glucose and blood pressure control but also include effective weight loss strategies.

Pediatric Obesity: Primary Care Perspective and Prevention.

In 1997, the World Health Organization declared obesity a global epidemic. Despite multiple efforts, obesity rates have been exponentially increasing for the past few decades. In the last few years, obesity rates have reached an alarming number. Multiple factors play a role in pediatric obesity, such as diet, sedentarism, and poor sleep, as well as psychosocial and environmental factors. Pediatricians and primary care providers are key in the management of overweight and obesity. They have the advantage of observing children over a long period of time, having a family centered perspective, and often being seen as a reliable source of information. Studies have shown that not only is obesity underdiagnosed, but there is a lack of knowledge among physicians and available resources regarding pediatric obesity. This article reviews the principles of prevention in a primary care outpatient setting. Additionally, it discusses some of the challenges commonly faced when addressing pediatric obesity. [Pediatr Ann. 2023;52(2):e51-e56.].

Limited Bariatric Surgery-induced Weight Loss in Subjects With Type 2 Diabetes: Predictor Variables in Adipose Tissue.

CONTEXT: The impact of type 2 diabetes mellitus (T2D) at baseline on limited weight loss (WL) after bariatric surgery (BS) remains controversial, and the potential underlying mechanisms incompletely understood. OBJECTIVE: We aimed at gaining further insight on this relationship and identifying novel associations between adipose tissue (AT) parameters and short-term WL outcomes in subjects with or without T2D undergoing BS. METHODS: Mid-term WL trajectories after BS have been evaluated in a cohort of 1659 subjects (cohort 1) with (n = 543) and without T2D (n = 1116). Paired subcutaneous and visceral AT samples were obtained from a cohort of 48 pairs of subjects with and without T2D matched for age, sex, BMI, and type of BS (cohort 2). Differences in AT parameters between groups were evaluated and potential associations with WL response explored. RESULTS: T2D was independently associated with a 5% lesser mid-term WL in cohort 1, while HbA1c, insulin treatment, and number of T2D medications prior to BS were only related to short-term WL outcomes. In cohort 2, a number of differentially expressed genes in AT were identified between groups, while fat cell size and fibrosis were comparable. Subcutaneous ATG7 expression was found as an independent predictor of limited WL 1 year after surgery (ß: -12.21 ± 4.41, P = .008) and its addition to a clinical model significantly improved the amount of WL variability explained (R2 = 0.131 vs R2 = 0.248, F change P = .009). CONCLUSION: Our results highlight the importance of T2D as determinant of limited WL following BS and suggest that dysregulated macroautophagy in subcutaneous AT may contribute to this association.

Exocrine pancreatic insufficiency following bariatric surgery: unveiling alternative aetiology-case report and short review.

Bariatric surgery (BS) is currently the most effective treatment for severe obesity, requiring ongoing multidisciplinary follow-up to ensure proper progress and nutrition post-procedure. Despite its favourable safety profile, it is not exempt from complications, one of which being exocrine pancreatic insufficiency (EPI). The underlying pathophysiological mechanisms of EPI after BS are multifactorial, including poorly synchronized pancreatic enzyme secretion with the passage of nutrients (pancreaticocibal or postcibal asynchrony), insufficient pancreatic stimulation and bacterial overgrowth. We conducted a short literature review of the topic through a case of a patient who underwent BS in our centre and subsequently developed EPI and severe malnutrition. EPI initially was attributed to the surgery, but after a comprehensive evaluation, an unexpected cause was revealed.

Effects of Bariatric Surgery on Blood and Vascular Large Extracellular Vesicles According to Type 2 Diabetes Status.

CONTEXT: Large extracellular vesicles (lEVs) enriched for endothelial and blood cell markers are increased in metabolic conditions such as obesity or type 2 diabetes (T2D), actively contribute to the atherosclerotic process, and have been identified as diagnostic and prognostic biomarkers for cardiovascular disease (CVD). Although bariatric surgery (BS) in individuals with obesity is related to decreased cardiovascular (CV) risk and increased life expectancy, after BS these subjects are still at higher CV risk than the general population. OBJECTIVE: We aimed to compare the lEV profiles between individuals with obesity, with or without T2D, before and 1 year after BS, and normal-weight controls. METHODS: Prospective longitudinal study with individuals eligible for BS, with or without T2D (T2D and OB groups, respectively) and healthy controls (HC group) matched by age and sex. The concentration and phenotype of lEVs were assessed by flow cytometry. RESULTS: The study cohort included 108 individuals (age 48.0 ± 10.5 years; 84.3% females). Before BS, the OB group presented higher concentrations of lEV enriched for endothelial and blood cell biomarkers than the HC group, but lower concentrations than those observed in the T2D group (P < .05). BS resulted in a significant reduction in most of the lEVs enriched for cell-specific markers in both subgroups. lEV differences between OB and T2D groups were no longer observed after BS (P > .05). However, compared with HC group, OB and T2D groups still showed increased concentrations of lEVs enriched for platelet and endothelial cell markers (P < .05). CONCLUSION: At 1 year after BS, lEV concentrations remain above the physiological range. These abnormalities might contribute to explaining the increased CV risk after BS and underscore the importance of long-term CV risk factor control in post-BS individuals.