Lessons from bariatric surgery: Can increased GLP-1 enhance vascular repair during cardiometabolic-based chronic disease?

Type 2 diabetes (T2D) and obesity represent entangled pandemics that accelerate the development of cardiovascular disease (CVD). Given the immense burden of CVD in society, non-invasive prevention and treatment strategies to promote cardiovascular health are desperately needed. During T2D and obesity, chronic dysglycemia and abnormal adiposity result in systemic oxidative stress and inflammation that deplete the vascular regenerative cell reservoir in the bone marrow that impairs blood vessel repair and exacerbates the penetrance of CVD co-morbidities. This novel translational paradigm, termed 'regenerative cell exhaustion' (RCE), can be detected as the depletion and dysfunction of hematopoietic and endothelial progenitor cell lineages in the peripheral blood of individuals with established T2D and/or obesity. The reversal of vascular RCE has been observed after administration of the sodium-glucose cotransporter-2 inhibitor (SGLT2i), empagliflozin, or after bariatric surgery for severe obesity. In this review, we explore emerging evidence that links improved dysglycemia to a reduction in systemic oxidative stress and recovery of circulating pro-vascular progenitor cell content required for blood vessel repair. Given that bariatric surgery consistently increases systemic glucagon-like-peptide 1 (GLP-1) release, we also focus on evidence that the use of GLP-1 receptor agonists (GLP-1RA) during obesity may act to inhibit the progression of systemic dysglycemia and adiposity, and indirectly reduce inflammation and oxidative stress, thereby limiting the impact of RCE. Therefore, therapeutic intervention with currently-available GLP-1RA may provide a less-invasive modality to reverse RCE, bolster vascular repair mechanisms, and improve cardiometabolic risk in individuals living with T2D and obesity.

A Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) from Human Blood: A Prospective Treatment for the COVID-19-Induced Cytokine Storm.

BACKGROUND Autologous blood-derived products can target specific inflammatory molecular pathways and have potentially beneficial therapeutic effects on inflammatory pathologies. The purpose of this study was to assess in vitro the anti-inflammatory and anti-catabolic potential of an autologous blood product as a possible treatment for COVID-19-induced cytokine storm. MATERIAL AND METHODS Blood samples from healthy donors and donors who had recovered from COVID-19 were incubated using different techniques and analyzed for the presence of anti-inflammatory, anti-catabolic, regenerative, pro-inflammatory, and procatabolic molecules. RESULTS The highest concentrations of therapeutic molecules for targeting inflammatory pathways were found in the blood that had been incubated for 24 h at 37°C, whereas a significant increase was observed after 6 h of incubation in blood from COVID-19-recovered donors. Beneficially, the 6-h incubation process did not downregulate anti-COVID-19 immunoglobulin G concentrations. Unfortunately, increases in matrix metalloproteinase 9, tumor necrosis factor alpha, and interleukin-1 were detected in the product after incubation; however, these increases could be blocked by adding citric acid, with no effect on the concentration of the target therapeutic molecules. Our data allow for safer and more effective future treatments. CONCLUSIONS An autologous blood-derived product containing anti-inflammatory and anti-catabolic molecules, which we term Cytorich, has a promising therapeutic role in the treatment of a virus-induced cytokine storm, including that associated with COVID-19.

Sodium-glucose cotransporter 2 inhibitors and type 2 diabetes: clinical pearls for in-hospital initiation, in-hospital management, and postdischarge.

PURPOSE OF REVIEW: The aim of this article is to provide practical recommendations on safe initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors to in-patients as well as management of those who are already on SGLT2 inhibitors. RECENT FINDINGS: Robust data from stable outpatient cohorts indicate that the SGLT2 inhibitors are associated with clinically meaningful reductions in major adverse cardiovascular events, lower rates of hospitalization for heart failure, and a reduction in major kidney outcomes There is however a lack of information on how to initiate and manage SGLT2 inhibitors in an acute in-patient setting. SUMMARY: SGLT2 inhibitors may be cautiously appropriate for in-patients if all the criteria for safe use are met but good clinical judgment must prevail. Temporary withholding of SGLT2 inhibitors is appropriate in hospitalized patients during a period of stress and/or insulinopenia.

Impact of COVID-19 pandemic on sleep parameters and characteristics in individuals living with overweight and obesity.

Coronavirus disease 2019 (COVID-19) has been very challenging for those living with overweight and obesity. The magnitude of this impact on sleep requires further attention to optimise patient care and outcomes. This study assessed the impact of the COVID-19 lockdown on sleep duration and quality as well as identify predictors of poor sleep quality in individuals with reported diagnoses of obstructive sleep apnoea and those without sleep apnoea. An online survey (June-October 2020) was conducted with two samples; one representative of Canadians living with overweight and obesity (n = 1089) and a second of individuals recruited through obesity clinical services or patient organisations (n = 980). While overall sleep duration did not decline much, there were identifiable groups with reduced or increased sleep. Those with changed sleep habits, especially reduced sleep, had much poorer sleep quality, were younger, gained more weight and were more likely to be female. Poor sleep quality was associated with medical, social and eating concerns as well as mood disturbance. Those with sleep apnoea had poorer quality sleep although this was offset to some degree by use of CPAP. Sleep quality and quantity has been significantly impacted during the early part of the COVID-19 pandemic in those living with overweight and obesity. Predictors of poor sleep and the impact of sleep apnoea with and without CPAP therapy on sleep parameters has been evaluated. Identifying those at increased risk of sleep alterations and its impact requires further clinical consideration.

Weight gain, weight management and medical care for individuals living with overweight and obesity during the COVID-19 pandemic (EPOCH Study).

Objective: Medical care and weight related experiences have been challenged by the coronavirus disease 2019 (COVID-19) pandemic for those living with obesity. The magnitude of this impact requires further attention in order to optimize patient care and outcomes. The aim of this study was to assess the impact of the COVID-19 pandemic and lockdown on access to, and experience of, medical care, weight gain and management strategies, as well as predictors of weight gain. Methods: An online survey (June-October 2020) was conducted with two samples; one representative of Canadians living with overweight and obesity (n = 1089) and a second of individuals recruited through obesity clinical services or patient organizations (n = 980). Results: Less than half of the total respondents thought that their providers were available for their medical care and most preferred in-person appointments over telemedicine. Only one quarter were satisfied with their obesity care. Sixty percent of the respondents reported weight gain (on average 5.65 kilograms [kg] gained), with 39.0% gaining more than 5% of their body weight (10.2% gained more than 10%). Over half of the respondents experienced decreased motivation for healthy eating or exercise. One third experienced more frequent and greater food consumption. Although worsening sleep occurred in approximately 20%, there was no significant increase in smoking, alcohol, or cannabis use. Predictors of weight gain were younger patients, higher weight categories, those who struggled with obtaining medical care during the pandemic, as well as those who struggled with eating. Conclusion: These results suggest that the COVID-19 pandemic negatively impacted patient care for those living with overweight and obesity and was associated with weight gain and interfered with weight management strategies. Greater attention to personalized weight management and interventions that focus on the predictors of weight gain should be undertaken.

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects with severe obesity, suggesting the restoration of a microenvironment to support vessel homeostasis. These data suggest that bariatric surgery may reverse deleterious events that predispose patients with morbid obesity to cardiovascular risk.

The Evaluation of Screening Questionnaires for Obstructive Sleep Apnea to Identify High-Risk Obese Patients Undergoing Bariatric Surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is extremely common among bariatric surgical candidates. Identifying those at risk for moderate to severe OSA is challenging. Testing all bariatric surgical candidates with a level 1 polysomnographic study is expensive and resource intensive. The aim of this study is to evaluate three standardized screening questionnaires that are utilized to identify high-risk patients for OSA undergoing bariatric surgery. METHODS: A retrospective review of data collected prospectively was undertaken on bariatric surgical patients who have not had a preexisting diagnosis of OSA. Each patient was subjected to the STOP BANG and Berlin Questionnaires as well as the Epworth Sleepiness Scale (ESS), after which a level 1 polysomnogram was undertaken. Nonparametric receiver operating characteristic analyses were used to evaluate the relationship between questionnaire scores and OSA as determined by a formal sleep lab study. RESULTS: There were 266 patients subjected to a standard overnight polysomnogram and screening questionnaires. Area under the curve (AUC) values for analyses including the entire sample were significantly (p < .05) greater than chance (i.e., AUC = .50) for all questionnaire scores except the ESS for both severe OSA (AUC range = .584-.631) and moderate/severe OSA (AUC range = .589-.660), although the magnitude of the AUC values was quite modest. Sensitivity and specificity values from the current study are substantially lower than those previously reported in the literature. CONCLUSIONS: Neither the STOP BANG nor Berlin questionnaires appear to be effective tools for detecting moderate- or high-risk patients for OSA undergoing bariatric surgery.

Inequity to the utilization of bariatric surgery: a systematic review and meta-analysis.

This systematic review explores the sociodemographic factors associated with the utilization of bariatric surgery among eligible patients. Electronic databases were searched for population-based studies that explored the relationship between sociodemographic characteristics of patients eligible for bariatric surgery to those who actually received the procedure. Twelve retrospective cohort studies were retrieved, of which the results of 9 studies were pooled using a random effects model. Patients who received bariatric surgery were significantly more likely to be white versus non-white (OR 1.54; 95% CI 1.08, 2.19), female versus male (OR 2.80; 95% CI 2.46, 3.22), and have private versus government or public insurance (OR 2.51; 95% CI 1.04, 6.05). Prospective cohort studies are warranted to further determine the relative effect of these factors, adjusting for confounding factors.