IMPACT OF BARIATRIC SURGERY ON CARDIOMETABOLIC AND NUTRITIONAL STATUS: PROS AND CONS

Extensive evidence supports the efficacy of bariatric surgery in reducing body weight and obesity-related comorbidities in severely obese patients. The present project was designed to assess the impact of bariatric surgery on clinically-relevant outcomes and to highlight the pros and cons of this therapeutic tool on specific metabolic, cardiovascular and nutritional aspects. In our studies, we found a significant improvement of glucose and lipid homeostasis in obese T2DM patients 1-2 years after bariatric surgery. The rate of diabetes remission at 1 year was 76% after SG and 86% after RYGB and the two major determinants of glucose homeostasis, i.e. beta cell function and insulin sensitivity, improved to a similar extent after either procedures. These results were achieved in the face of a different pattern of GI hormone profile, suggesting that weight loss and the consequent improvement of insulin sensitivity are the main determinants of diabetes remission, at least several months after surgery. Interestingly, while plasma triglycerides decreased to a similar extent with the two procedures, total and LDL-cholesterol decreased more consistently after RYGB than SG; furthermore, the decrease in LDL-cholesterol was inversely related to meal-induced GLP-1 response suggesting that GLP-1 restoration is crucial for the improvement of cholesterol metabolism, possibly through an increase in circulating bile acids. The overall metabolic improvement induced by bariatric surgery translates into clear benefits in terms of cardiovascular risk. Indeed, we have documented a reduction in carotid intima-media thickness and an increase in endothelial function after bariatric procedures. These changes in markers of subclinical atherosclerosis are in line with the reduction in cardiovascular morbidity and mortality, consistently shown by large population studies. Thus, the cardioprotective effects of bariatric surgery range from improvement in early signs of subclinical atherosclerosis to prevention of major fatal and non-fatal cardiovascular and cerebrovascular events. Further extending this finding, we have documented that bariatric surgery is able to improve the obesity-related hypercoagulable state characterized by increased levels of clotting factors and impaired fibrinolysis. However, it is important to note that at 2-month post-operative follow-up, we observed a significant decrease in natural anticoagulants, probably due to reduction of vitamin K absorption. This decrease could potentially lead to increased thrombotic risk. Since our data have been obtained in the early post-operative phase, no definite conclusion on the long-term effect of bariatric surgery on coagulant/anticoagulant balance can be drawn. Despite the proven efficacy of bariatric surgery in improving overall metabolic control and reducing total and cardiovascular mortality, some concerns can be raised regarding two main points: 1) increased glucose variability and 2) alterations of nutritional status. With regard to the former, we have found that some patients classified as diabetes remitters according to currently validated criteria, suffer from high glycemic variability, i.e., they present ample glucose excursions throughout the day, often reaching frank hypoglycemic threshold. This alteration is likely to be underdiagnosed since it can be detected only by continuous glucose monitoring. Even more interesting is the observation that high GV is associated with increased oxidative stress, indicating an increased risk of vascular damage. Based on these findings, we propose that GV be included among criteria for the definition of diabetes remission in order to have a comprehensive picture of the impact of bariatric surgery on glucose homeostasis. Furthermore, since high GV is likely involved in the pathogenesis of vascular complications and mortality risk, at least in diabetic patiens, ad hoc studies should be performed to identify and to manage appropriately glycemic variability. Of great interest is the possibility to reduce GV by proper nutritional measures, such as low-glycemic index food. The latter issue is one that involves nutrient deficiencies. Several studies have consistently documented a high prevalence of vitamin and mineral deficiencies after bariatric procedures. Poor postoperative nutrient intake, recurrent vomiting, inadequate supplementation are important risk factors. In addition, reviewing the available literature, we have documented that a considerable number of obese patients present vitamin and/or micronutrient deficiencies already before surgery, vitamin D deficit being the most frequent abnormality (about 60%). The high prevalence of pre-operative nutritional deficiency underlines the need of a careful nutritional screening in all patients scheduled for bariatric surgery in order to detect and correct any possible deficiency before intervention. Likewise, effective strategies should be implemented to improve long-term patients’ adherence to lifestyle and nutritional recommendations in order to maximize the benefits of bariatric surgery and reducing the risk of the above discussed complications

Cardiovascular risk markers in patients with primary aldosteronism: A systematic review and meta-analysis of literature studies

Background/objectives: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. Methods: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P<0.00001), and a higher aortic-PWV (272 cases and 240 controls, MD: 1.39 m/s; 95% CI: 0.90, 1.87; P<0.00001). In contrast, non-significant differences were found in AIx and AIx normalized to a heart rate of 75 beats per minute (AIx@75). When compared to normotensive subjects, PA patients showed significantly higher CCA-IMT (MD: 0.16 mm; 95% CI: 0.05, 0.27; P=0.004), aortic-PWV (MD: 3.74 m/s; 95% CI: 3.43, 4.05; P<0.00001), AIx@75 (MD: 8.59%; 95% CI: 0.69, 16.50; P=0.03), and a significantly lower FMD (MD: -2.52%; 95% CI: -3.64, -1.40; P<0.0001). Sensitivity and subgroup analyses substantially confirmed our results. Metaregression models showed that male gender, diabetes, and smoking habit impact on the observed results. Conclusions: PA appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting

Haemostatic and fibrinolytic changes in obese subjects undergoing bariatric surgery: the effect of different surgical procedures.

Background Little is known about effects of different bariatric surgery procedures on haemostatic and fibrinolytic parameters. Material and methods Consecutive obese subjects undergoing gastric bypass (GBP) or sleeve gastrectomy (SG) were enrolled. In all patients, levels of haemostatic factors (FII, FVII, FVIII, FIX, FX, vWF, fibrinogen), fibrinolytic variables (PAI-1, t-PA and D-dimer) and natural anticoagulants (AT, protein C and protein S) were evaluated before and 2 months after surgery. Results A total of 77 GBP and 79 SG subjects completed the study. At baseline no difference in coagulation parameters was found between the two groups. After both GBP and SG, subjects showed significant changes in haemostatic and fibrinolytic variables and in natural anticoagulant levels. The Δ% changes in FVII, FVIII, FIX, vWF, fibrinogen, D-dimer, protein C and protein S levels were significantly higher in subjects who underwent GBP than in those who underwent SG. Multivariate analysis confirmed that GBP was a predictor of higher Δ% changes in FVII (β=0.268, p=0.010), protein C (β=0.274, p=0.003) and protein S (β=0.297, p<0.001), but not in all the other variables. Following coagulation factor reduction, 31 subjects (25.9% of GBP and 13.9% of SG; p=0.044) showed overt FVII deficiency; protein C deficiency was reported by 34 subjects (32.5% of GBP vs 11.4% of SG, p=0.033) and protein S deficiency by 39 (37.6% of GBP vs 12.6% of SG, p=0.009). Multivariate analyses showed that GBP was associated with an increased risk of deficiency of FVII (OR: 3.64; 95% CI: 1.73–7.64, p=0.001), protein C (OR: 4.319; 95% CI: 1.33–13.9, p=0.015) and protein S (OR: 5.50; 95% CI: 1.71–17.7, p=0.004). Discussion GBP is associated with an increased risk of post-operative deficiency in some vitamin K-dependent coagulation factors. Whereas such deficiency is too weak to cause bleeding, it is significant enough to increase the risk of thrombosis

Lipid profile changes in patients with rheumatic diseases receiving a treatment with TNF-α blockers: a meta-analysis of prospective studies.

Some studies showed an anti-atherogenic effect of TNF-α blockers on lipid profile, but these data have been challenged.To perform a meta-analysis on lipid profile changes induced by TNF-α blocker treatment.Prospective studies on rheumatic patients receiving TNF-α blockers and providing before-and-after treatment values of triglycerides (TGs), total cholesterol (TC), HDL-cholesterol (HDLc), LDL-cholesterol (LDLc), and atherogenic index (AI) were included. Standardized mean differences (SMD) in lipid profile were analyzed at short-term (2-12 weeks), middle-term (13-24 weeks), and long-term (25-52 weeks) assessments.Thirty articles (1707 patients) were included. TNF-α blockers determined an increase in TC at short-term, middle-term, and long-term assessments (SMD: 0.20 mmol/L [95% CI: 0.04, 0.35]; SMD: 0.27 mmol/L [95% CI: 0.08, 0.46]; SMD: 0.22 mmol/L [95% CI: 0.01, 0.43]). HDLc increased only at the short-term assessment (SMD: 0.19 mmol/L [95% CI: 0.10, 0.28]), and TGs achieved a significant increase at the long-term assessment (SMD: 0.19 mmol/L [95% CI: 0.04, 0.34]). LDLc and AI were not affected by TNF-α blocker treatment.Slight but significant increases in TC occurred without any significant change in LDLc and AI. Changes in HDLc and TGs were not consistent among the different time point assessments. These quantitative changes in lipid profile do not seem to be able to explain cardiovascular risk improvement reported in patients receiving TNF-α blockers. Further studies on other mechanisms are needed to address this issue

Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia: Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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Gut microbiome and blood glucose control in type 1 diabetes: a systematic review

ObjectiveThe risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D.MethodsGoogle Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: “gut microbiota,” “gut microbiome,” “bacteria,” “T1D,” “type 1 diabetes,” “autoimmune diabetes,” “glycemic control,” “glucose control,” “HbA1c,” “inflammation,” “inflammatory,” and “cytokine.” The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients.ResultsThis review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients.ConclusionWe draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders