Metabolic variables of obese dogs with insulin resistance supplemented with yeast beta-glucan

Background Obesity is one of the most common nutritional disorders in dogs and cats and is related to the development metabolic comorbidities. Weight loss is the recommended treatment, but success is difficult due to the poor satiety control. Yeast beta-glucans are known as biological modifiers because of their innumerable functions reported in studies with mice and humans, but only one study with dogs was found. This study aimed to evaluate the effects of a diet supplemented with 0.1% beta-glucan on glucose, lipid homeostasis, inflammatory cytokines and satiety parameters in obese dogs. Fourteen dogs composed three experimental groups: Obese group (OG) with seven dogs with body condition score (BCS) 8 or 9; Lean group (LG) included seven non-obese dogs with a BCS of 5; and Supplemented Obese group (SOG) was the OG dogs after 90 days of consumption of the experimental diet. Results Compared to OG, SOG had lower plasma basal glycemic values (p = 0.05) and reduced serum cholesterol and triglyceride levels. TNF-α was lower in SOG than in OG (p = 0.05), and GLP-1 was increased in SOG compared to OG and LG (p = 0.02). Conclusion These results are novel and important for recognizing the possibility of using beta-glucan in obesity prevention and treatment.

Programming of obesity and pediatric metabolic syndromes: a review in light of epigenetic modulation

Obesity is a multifactorial health problem characterized by the excessive accumulation of fat in the body and affects approximately 338 million children and adolescents worldwide. For this reason, this study consisted of a literature review to investigate how the causes and treatments of pediatric obesity are being addressed in light of epigenetic modulation as a factor in metabolic programming. For this, preferentially original articles published in English between the years 2017 to 2021 in the PubMed and Scholar Google databases were searched using the epigenetics descriptors; epigenetic modulation; child obesity; metabolic syndrome, combined with each other. A total of 54,000 articles were returned to searches in PubMed and 16,107,000 in Scholar Google. Fewer than 500 studies jointly addressed epigenetics and aspects of obesity or metabolic syndromes in childhood. Only 14 works matched the search criteria. The most discussed epigenetic mechanism in the literature is DNA methylation, whose rates observed mainly in CpG islands of promoter regions in several genes contribute to the prevention and early diagnosis of obesity and other pediatric comorbidities even before birth, based on the correlation between the epigenetic marks, maternal and paternal health and anthropometric indices. Although experimental studies on infant metabolic programming are scarce, existing knowledge suggests that environmental, nutritional, and energy expenditure changes are capable of modulating the epigenome and reversing marks that induce susceptibility to metabolic comorbidities.

Metabolic comorbidities among patients with peripheral artery disease: a national population-based study

Peripheral artery disease (PAD) is a chronic disease which is associated with old age. PAD was known as an age-related chronic condition. Metabolic comorbid conditions which include hypertension, diabetes, and hyperlipidemia can have negative impacts on blood vessels aggravating PAD in elderly patients. Therefore, metabolic comorbidities need be considered in order to develop intervention for patients with PAD. The aim of this study is to find the characteristics of PAD patients with metabolic comorbidities. This is a retrospective study that used the national claim data of South Korea from 2009 to 2018. The inclusion criteria were adults (20+) and patients diagnosed with PAD as a primary or secondary diagnosis from 2011 to 2017. The frequency of hypertension, hyperlipidemia, diabetes, and metabolic comorbidities in PAD patients was examined. In addition, the difference in the number of metabolic comorbidities according to sex was identified using the chi-squared test. Among the total PAD adult patients(n=8,478,876), the number of elderly patients over 60 years old was 4,124,592(48.7%). Among the total patients, PAD patients with hypertension were the most common at 958,329 (11.30%). Sex was significantly related to having metabolic comorbidities and women showed higher proportion of metabolic comorbidities compared to men (χ2 =5.02, p<.001). As the frequency of PAD patients with hypertension were the highest, it is necessary to develop a health management program that considers metabolic comorbidities, especially hypertension, in order to manage PAD disease. In addition, there is a need for special interest in intervening metabolic conditions of female patients with PAD.

Potential Transdiagnostic Lipid Mediators of Inflammatory Activity in Individuals With Serious Mental Illness

Mental disorders are heterogeneous and psychiatric comorbidities are common. Previous studies have suggested a link between inflammation and mental disorders. This link can manifest as increased levels of proinflammatory mediators in circulation and as signs of neuroinflammation. Furthermore, there is strong evidence that individuals suffering from psychiatric disorders have increased risk of developing metabolic comorbidities. Our group has previously shown that, in a cohort of low-functioning individuals with serious mental disorders, there is increased expression of genes associated with the NLRP3 inflammasome, a known sensor of metabolic perturbations, as well as increased levels of IL-1-family cytokines. In the current study, we set out to explore the interplay between disease-specific changes in lipid metabolism and known markers of inflammation. To this end, we performed mass spectrometry-based lipidomic analysis of plasma samples from low-functioning individuals with serious mental disorders (n = 39) and matched healthy controls (n = 39). By identifying non-spurious immune-lipid associations, we derived a partial correlation network of inflammatory markers and molecular lipids. We identified levels of lipids as being altered between individuals with serious mental disorders and controls, showing associations between lipids and inflammatory mediators, e.g., osteopontin and IL-1 receptor antagonist. These results indicate that, in low-functioning individuals with serious mental disorders, changes in specific lipids associate with immune mediators that are known to affect neuroinflammatory diseases.

Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis

Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients. Methods: A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88–3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16–4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71–2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed. Conclusions: this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components.

879. Evaluation of the Incidence of Hypertension, Diabetes, and Hyperlipidemia in Patients on Antiretroviral Therapy

Background Although integrase inhibitor (INSTI)-based regimens have been associated with weight gain, there is limited data on whether INSTIs cause long-term metabolic consequences. This study evaluated the effect of INSTIs on the development of metabolic comorbidities compared to non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based therapies in patients in the Illinois Department of Corrections. Methods This retrospective cohort study consisted of incarcerated adult patients living with HIV and receiving a guideline-recommended regimen between 7/12/10 and 12/31/19. Patients with a pre-existing diagnosis of diabetes, hypertension, or hyperlipidemia, or lack of medical follow-up data were excluded. The primary outcome was to compare the incidence of a metabolic comorbidity between regimens. Secondary outcomes compared the incidence of weight gain, diabetes, hypertension, and hyperlipidemia as separate outcomes between drug classes. Demographics and pertinent labs were collected. Data was analyzed with ANOVA, chi-squared, and paired t-tests. The primary outcome was adjusted for age, race, use of antipsychotic medications, and family history of metabolic comorbidities. Results A total of 206 patients were included in the analysis with mean follow-up time of 31.5 ± 19.4 months. Majority of patients were Black (69%) and male (91%). A total of 42 patients developed a metabolic comorbidity (Table 1). After adjustment for confounding factors, there was a significant difference in the development of comorbidities between the treatment groups (p=0.031) with INSTI use being more likely to develop a comorbidity than NNRTI (p=0.004). No difference was found between INSTI and PI use (p=0.518). Development of hypertension was significantly higher in the INSTI group than NNRTI group (p=0.014), while the development of diabetes and hyperlipidemia were not. Weight and BMI were significantly higher regardless of antiretroviral (Table 2). No differences were found in the primary outcome between agents within the same drug class or between 1st or 2nd generation INSTIs. Table 1. Results of Primary and Secondary Outcomes Table 2. Impact of HIV regimen on weight and BMI after 1 year Conclusion All antiretrovirals were linked to weight gain but INSTIs were associated with increased incidence of hypertension. Disclosures All Authors: No reported disclosures

69. Incidence of metabolic complications among treatment-naïve adults living with HIV-1 randomized to B/F/TAF, DTG/ABC/3TC or DTG+F/TAF after 144 Weeks

Background Metabolic comorbidities including diabetes (DM) and dyslipidemia pose challenges to the long-term care of people with HIV (PWH). Incidence of cardiovascular disease and DM are reported at higher rates in PWH than the general population. Obesity is broadly prevalent in both the general population and PWH, and higher body mass index (BMI) can contribute to metabolic complications. Here we present longer-term follow up on incidence of DM, hypertension (HTN), BMI categorical shifts, and lipid changes over 144 weeks of blinded treatment from two trials of PWH initiating antiretroviral therapy. Methods We assessed incidence of metabolic complications in adult PWH in Study 1489: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir/abacavir/ lamivudine (DTG/ABC/3TC) and Study 1490: B/F/TAF vs DTG+F/TAF. Treatment-emergent (TE) metabolic comorbidities were defined by standard MedDRA search lists. CDC-defined BMI categories were compared from baseline (BL) to Week 144. Analyses by sex at birth and race were performed, as well as for lipid changes. Results Among 1,274 total participants, median (range) age was 33 years (18-77), 90% men, 33% black. In study 1489, BL prevalence of DM and HTN was 4.5 and 12.1% with TE DM and HTN in B/F/TAF being 0.7% and 10%, and for DTG/ABC/3TC 1.3% and 6.9%, respectively. In study 1490, BL prevalence of DM and HTN was 6.8 and 18.8% with TE DM and HTN in B/F/TAF being 2.1 and 5.8%, and for DTG+F/TAF 2.3 and 6.5%, respectively. BMI shift from Normal to Obese: B/F/TAF 0%, DTG/ABC/3TC 3.2%, p=0.12 (1489) (Table 1); B/F/TAF 2.5%, DTG+F/TAF 2.9% p=1.00 (1490) (Table 2). Subgroup analyses by gender/race showed similar findings for TE DM, HTN, and BMI changes. Median changes from BL fasted lipids were small (Table 1). Table 1§. Studies 1489 and 1490: Metabolic Outcomes from Baseline to Week 144 Table 2±. Shift Table of BMI Category at Week 144 by Baseline BMI Category – Overall Conclusion Through over 144 weeks of follow up, PWH randomized to initiate B/F/TAF, DTG/ABC/3TC or DTG+F/TAF had low rates of incident DM or HTN-related AEs, with no statistically significant differences by treatment group. BMI changes/categorical shifts from BL did not significantly differ by regimen, and no clinically significant change or difference by regimen in lipids were observed. While data are limited by three years of follow up, they are strengthened by randomized study design of three widely used initial ART regimens. Disclosures Eric Daar, MD, Bristol-Myers Squibb (Consultant)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)Janssen (Consultant, Advisor or Review Panel member, Research Grant or Support)Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Teva (Consultant, Advisor or Review Panel member)ViiV Healthcare (Consultant, Advisor or Review Panel member, Research Grant or Support) Chloe Orkin, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Other Financial or Material Support)Janssen (Research Grant or Support, Other Financial or Material Support)Merck (Research Grant or Support, Other Financial or Material Support)ViiV Healthcare (Research Grant or Support, Other Financial or Material Support) Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) Jeffrey L. Stephens, MD, Gilead Sciences Inc. (Scientific Research Study Investigator, Research Grant or Support) Ellen Koenig, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Amanda Clarke, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Conference attendance sponsorship)ViiV Healthcare (Consultant, Other Financial or Material Support, Conference travel sponsorship) Axel Baumgarten, MD, AbbVie (Advisor or Review Panel member, Speaker’s Bureau)Bristol-Myers Squibb (Advisor or Review Panel member, Speaker's Bureau)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau)Janssen (Speaker’s Bureau)Merck (Advisor or Review Panel member) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Hailin Huang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Terry Farrow, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) Jason Hindman, PharmD, Gilead Sciences Inc. (Employee, Shareholder) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder) Kimberly Workowski, MD, Nothing to disclose