Metabolic Health Effects Research Articles

System genetic analysis of intestinal cancer and periodontitis development as influenced by aging and diabesity using Collaborative Cross mice.

It is increasingly recognized that young, chow-fed inbred mice poorly model the complexity of human carcinogenesis. In humans, age and adiposity are major risk factors for malignancies, but most genetically engineered mouse models (GEMM) induce carcinogenesis too rapidly to study these influences. Standard strains, such as C57BL/6, commonly used in GEMMs, further limit the exploration of aging and metabolic health effects. A similar challenge arises in modeling periodontitis, a disease influenced by aging, diabesity, and genetic architecture. We propose using diverse mouse populations with hybrid vigor, such as the Collaborative Cross (CC) × ApcMin hybrid, to slow disease progression and better model human colorectal cancer (CRC) and comorbidities. This perspective highlights the advantages of this model, where delayed carcinogenesis reveals interactions with aging and adiposity. Unlike ApcMin mice, which develop cancer rapidly, CC × ApcMin hybrids recapitulate human-like progression. This facilitates the identification of modifier loci affecting inflammation, diet susceptibility, organ size, and polyposis distribution. The CC × ApcMin model offers a transformative platform for studying CRC as a disease of adulthood, reflecting its complex interplay with aging and comorbidities. The insights gained from this approach will enhance early detection, management, and treatment strategies for CRC and related conditions.

Nonylphenol and Cetyl Alcohol Polyethoxylates Disrupt Thyroid Hormone Receptor Signaling to Disrupt Metabolic Health.

Surfactants are molecules with both hydrophobic and hydrophilic structural groups that adsorb at the air-water or oil-water interface and serve to decrease the surface tension. Surfactants combine to form micelles that surround and break down or remove oils, making them ideal for detergents and cleaners. Two of the most important classes of nonionic surfactants are alkylphenol ethoxylates (APEOs) and alcohol ethoxylates (AEOs). APEOs and AEOs are high production-volume chemicals that are used for many industrial and residential purposes, including laundry detergents, hard-surface cleaners, paints, and pesticide adjuvants. Commensurate with better appreciation of the toxicity of APEOs and the base alkylphenols, use of AEOs has increased, and both sets of compounds are now ubiquitous environmental contaminants. We recently demonstrated that diverse APEOs and AEOs induce triglyceride accumulation and/or preadipocyte proliferation in vitro. Both sets of contaminants have also been demonstrated as obesogenic and metabolism-disrupting in a developmental exposure zebrafish model. While these metabolic health effects are consistent across models and species, the mechanisms underlying these effects are less clear. This study sought to evaluate causal mechanisms through reporter gene assays, relative binding affinity assays, coexposure experiments, and use of both human cell and zebrafish models. We report that antagonism of thyroid hormone receptor signaling appears to mediate at least a portion of the polyethoxylate-induced metabolic health effects. These results suggest further evaluation is needed, given the ubiquitous environmental presence of these thyroid-disrupting contaminants and reproducible effects in human cell models and vertebrate animals.

NBF2, an Algal Fiber-Rich Formula, Reverses Diabetic Dyslipidemia and Hyperglycemia In Vivo.

Ulva prolifera, known as Aonori in Japan, is an edible alga species that is mass-cultivated in Japan. Supplementation with Aonori-derived biomaterials has been reported to enhance metabolic health in previous studies. This was an experimental study that evaluated the metabolic health effects of NBF2, a formula made of algal and junos Tanaka citrus-derived biomaterials, on obesity and type 2 diabetes (T2DM). We used 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats that were assigned randomly to three groups of six animals: a high-dose NBF2 drink (20 mg/kg) group, a low-dose (10 mg/kg) NBF2 drink group and the control group that received 2 mL of tap water daily for a total of six weeks. We also used eight LETO rats as the normal control group. In addition to the glucose tolerance test (OGTT), ELISA and real-time PCR assays were performed. High-dose and lowdose NBF2 improved insulin sensitivity, as well as glycemic and lipid profiles, as compared with control rats. The OGTT showed that both NBF2 groups and LETO rats had normalized glycemia by the 90-min time-point. NBF2 up-regulated PPARα/γ-mRNA and Sirt2-mRNA gene expressions in BAT and improved the blood pressure profile. These findings suggest that the NBF2 formula, which activates PPAR-α/γ mRNA and Sirt2-mRNA, may reverse dyslipidemia and hyperglycemia in T2DM.

Childhood adversity, accelerated GrimAge, and associated health consequences.

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

Unmasking metabolic disruptors: The NEMESIS project's quest for Novel Biomarkers, Evidence on Adverse Effects, and Efficient Methodologies

Metabolism disrupting chemicals (MDCs) elicit negative effects on metabolically active organs such as the liver and the pancreas, altering normal metabolic processes. Chemicals that are known, or suspected MDCs include compounds found in everyday consumer products and food, making low-dose, continuous exposure inevitable for humans. Through the discovery of chemically induced metabolic disruption, a concern has surfaced whether and how MDCs impact human health and the development of metabolic diseases. This has accelerated research around the topic, and it has been found that exposure to MDCs is linked to increased incidence of metabolic diseases including obesity and liver steatosis. Effective regulatory action is hindered by the lack of accurate methods to identify MDCs. The NEMESIS project addresses this regulatory gap by investigating the mechanisms through which MDCs cause metabolic disruption. The project aims at identifying novel biomarkers of exposure and link exposure to disease outcomes. As chemical toxicity testing is rapidly moving towards new approach methodologies (NAMs), NEMESIS promotes non-animal methodologies by employing state-of-the-art in vitro methods, epidemiological data, systems biology approaches, and seeks to replace mammalian in vivo experiments with alternative models. By understanding mechanisms of MDC-induced metabolic health effects, and through the development of reliable effect biomarkers and testing strategies, the NEMESIS project aims to facilitate more effective regulatory measures to improve and protect the health and well-being of EU citizens. The project is particularly focused on maximizing its impact through effective dissemination and communication efforts, to ensure that the project’s message and results reach a broad audience and are tailored to different population groups. These actions will improve the risk assessment of MDCs and ensure that the EU citizens are informed and protected from the harmful effects of MDCs and can adapt their consumer patterns and behaviors to prevent exposure.

Unraveling the Distribution, Metabolization, and Catabolism of Foliar Sprayed Carbon Dots in Maize and Effect on Soil Environment.

The enormous potential of carbon dots (CDs) in agriculture has been widely reported, whereas their accurate distribution, transformation, and metabolic fate and potential soil health effects are not clearly understood. Herein, 13C-labeled CDs (13C-CDs) were sprayed on maize leaf, accumulated in all tissues, and promoted photosynthesis. Specifically, 13C-CDs were internalized to participate in the synthesis of glucose, sucrose, citric acid, glyoxylate, and chlorogenic acid, promoting tricarboxylic acid cycle (TCA) and phenylalanine metabolism. Additionally, the catabolism of 13C-CDs in vivo was mainly mediated by O2•- produced by oxidative stress. 13C-CDs did not have an obvious impact on the soil environment at the overall level. The detection of 13C signals in soil fauna suggested 13C-CDs in soil food chain transmission. This study systematically described the exact fate of CDs in plants and potential soil ecological risks and provided a more comprehensive analysis and support for the potential advantages of CDs in agricultural application.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Molecular Assessment of Proadipogenic Effects for Common-Use Contraceptives and Their Mixtures.

Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the United States, approximately 65% of reproductive-aged women are estimated to be using contraceptive options, with approximately 33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential effect on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects. As such, the goals of this study were to assess the adipogenic activity of common hormonal contraceptive chemicals and their mixtures. Five different models of adipogenesis were used to provide a rigorous assessment of metabolism-disrupting effects. Interestingly, every individual contraceptive (both estrogens and progestins) and each mixture promoted significant adipogenesis (eg, triglyceride accumulation and/or preadipocyte proliferation). These effects appeared to be mediated in part through estrogen receptor signaling, particularly for the contraceptive mixtures, as cotreatment with fulvestrant acted to inhibit contraceptive-mediated proadipogenic effects on triglyceride accumulation. In conclusion, this research provides valuable insights into the complex interactions between hormonal contraceptives and adipocyte development. The results suggest that both progestins and estrogens within these contraceptives can influence adipogenesis, and the specific effects may vary based on the receptor disruption profiles. Further research is warranted to establish translation of these findings to in vivo models and to further assess causal mechanisms underlying these effects.

Intertwined relationship of dynamin-related protein 1, mitochondrial metabolism and circadian rhythm.

In recent years, mitochondria have gained significant interest in the field of biomedical research due to their impact on human health and ageing. As mitochondrial dynamics are strongly controlled by clock genes, misalignment of the circadian rhythm leads to adverse metabolic health effects. In this review, by exploring various aspects of research and potential links, we hope to update the current understanding of the intricate relationship between DRP1-mediated mitochondrial dynamics and changes in circadian rhythmicity leading to health issues. Thus, this review addresses the potential bidirectional relationships between DRP1-linked mitochondrial function and circadian rhythm misalignment, their impact on different metabolic pathways, and the potential therapeutics for metabolic and systemic disorders.

350 Effects of GLP-1 Agonist on Pediatric Populations in a Real-World Setting

OBJECTIVES/GOALS: Compare metabolic health of type 2 diabetics on GLP-1 to those on traditional therapy METHODS/STUDY POPULATION: Outcomes of interest of this study include analyzing GLP-1 agonists on overall metabolic health, focusing primarily on weight loss and ability to wane off insulin without rebounding metabolic health. The data will be collected in a retrospective chart review from medical records of type II diabetics from Children’s of Alabama and will follow patients over two years. The charts have been narrowed to those patients prescribed GLP-1 agonists who have been on the medication for at least one year with consistent visits to the endocrinology clinic.The following data will be collected from the charts:race/ethnicity, date of visit, BMI/weight, A1C, insulin therapy, lipids, LFTs (AST/ALT), and insurance coverage RESULTS/ANTICIPATED RESULTS: With these results, we hope to study the metabolic health effects of GLP-1 agonists on type II diabetes in the pediatric population. It is known that obesity is a risk factor for type II diabetes, and that GLP-1 agonists aid in weight-loss in adults. Further research is needed to see the real world health effects, and with these results we hope to assess if GLP-1 agonist have an affect on metabolic health within the pediatric population by collecting data on values aforementioned. We also hope to compare and contrast the different GLP-1 agonists being used based on adherence, insurance coverage, adverse effects, and patient preference. Currently, only Liraglutide and Exetanide are approved for pediatric type II diabetics. DISCUSSION/SIGNIFICANCE: Insulin use can lead to weight gain; metformin does not aidin weight reductions. If GLP-1 agonists aid in weight loss, it could potentially help slow complications of diabetes in the pediatric population. B-cell function in children declines more rapidly; and, as a result, insulin resistance occurs more rapidly.

Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

Inflammatory biomarkers link perceived stress with metabolic dysregulation

ObjectivePerceived stress has been identified as a risk factor for metabolic syndrome. However, the intermediate pathways underlying this relationship are not well understood. Inflammatory responses may be one process by which stress leads to metabolic dysregulation. Prior work has shown that chronic stress is associated with elevated systemic inflammation and that altered inflammatory activity contributes to the pathogenesis of metabolic syndrome. The current analyses tested this hypothesis by examining inflammation as a pathway by which perceived stress affects metabolic health. MethodsData from the Midlife in the United States Study (MIDUS) (N = 648; Mean age = 52.3) provided measures of perceived stress, inflammatory biomarkers [C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, fibrinogen, intracellular adhesion molecule-1 (ICAM-1)] and metabolic health markers. Confirmatory factor analysis (CFA) was used to confirm the fit of a hierarchical model of metabolic syndrome in our sample. Structural equation modeling (SEM) was used to test the assumption that inflammation mediates the association between perceived stress and the latent factor representing metabolic syndrome. ResultsThe CFA of metabolic syndrome demonstrated excellent goodness of fit to our sample [CFI = 0.97, TLI = 0.95, RMSEA = 0.06, SMSR = 0.05]. Mediation analysis with SEM revealed that the indirect pathway linking stress to metabolic dysregulation through inflammation was significant [B = 0.08, SE = 0.01, z = 3.69, p < .001, 95% confidence interval CI (0.04, 0.13)]. ConclusionsThese results suggest that inflammatory biomarkers are a viable explanatory pathway for the relationship between perceived stress and metabolic health consequences. Interventions that target psychosocial stress may serve as cost-effective and accessible treatment options for mitigating inflammatory health risks.

Exposure to perfluoroalkyl and polyfluoroalkyl substances and risk of stroke in adults: ameta-analysis.

Evidence of the adverse metabolic health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) is increasing. However, the impact of PFAS on cardiovascular diseases remains controversial. This meta-analysis aimed to analyze the impact of PFAS on the stroke risk. Databases were searched for studies published up to November 1, 2022, which report the association between stroke and exposure to at least one of four main PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorononanoic acid [PFNA], and perfluorohexane sulfonic acid [PFHxS]). Data extraction and quality assessment were performed according to the Newcastle-Ottawa scale. Four studies were included in this systematic review. Multivariate adjusted odds ratios (ORs) for incident stroke per 1-log unit increment in each serum PFAS were combined in the meta-analysis. The risk of development of stroke was not significantly associated with PFOA, PFOS, or PFNA exposure (PFOA: pooled odds ratio [OR]=1.001, 95 % confidence interval [CI]=0.975-1.028, p=0.934; PFOS: pooled OR=0.994, 95 % CI=0.972-1.017, p=0.601; PFNA: pooled OR=1.016, 95 % CI=0.920-1.123, p=0.752), whereas a moderately lower risk was associated with PFHxS exposure without statistical significance (pooled OR=0.953, 95 % CI=0.908-1.001, p=0.054). PFOA, PFOS, and PFNA exposure showed a neutral association, while PFHxS showed a possible inverse association with the risk of stroke. Therefore, this finding should be interpreted with caution. Further prospective observational studies with PFAS mixture analyses are warranted.

Effects of Individual Circulating FFAs on Plasma and Hepatic FFA Epoxides, Diols, and Epoxide-Diol Ratios as Indices of Soluble Epoxide Hydrolase Activity.

Oxylipins, oxidation products of unsaturated free fatty acids (FFAs), are involved in various cellular signaling systems. Among these oxylipins, FFA epoxides are associated with beneficial effects in metabolic and cardiovascular health. FFA epoxides are metabolized to diols, which are usually biologically less active, by soluble epoxide hydrolase (sEH). Plasma epoxide-diol ratios have been used as indirect measures of sEH activity. This study was designed to examine the effects of acute elevation of individual plasma FFAs on a variety of oxylipins, particularly epoxides, diols, and their ratios. We tested if FFA epoxide-diol ratios are altered by circulating FFA levels (i.e., substrate availability) independent of sEH activity. Wistar rats received a constant intravenous infusion of olive (70% oleic acid (OA)), safflower seed (72% linoleic acid (LA)), and fish oils (rich in ω-3 FFAs) as emulsions to selectively raise OA, LA, and ω-3 FFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), respectively. As expected, olive, safflower seed, and fish oil infusions selectively raised plasma OA (57%), LA (87%), EPA (70%), and DHA (54%), respectively (p < 0.05 for all). Raising plasma FFAs exerted substrate effects to increase hepatic and plasma epoxide and diol levels. These increases in epoxides and diols occurred to similar extents, resulting in no significant changes in epoxide-diol ratios. These data suggest that epoxide-diol ratios, often used as indices of sEH activity, are not affected by substrate availability or altered plasma FFA levels and that epoxide-diol ratios may be used to compare sEH activity between conditions of different circulating FFA levels.

The effects of sleep disruption on metabolism, hunger, and satiety, and the influence of psychosocial stress and exercise: A narrative review.

Sleep deficiency is a ubiquitous phenomenon among Americans. In fact, in the United States, ∼78% of teens and 35% of adults currently get less sleep than recommended for their age-group, and the quality of sleep appears to be getting worse for many. The consequences of sleep disruption manifest in a myriad of ways, including insulin resistance and disrupted nutrient metabolism, dysregulation of hunger and satiety, and potentially increased body weight and adiposity. Consequently, inadequate sleep is related to an increased risk of various cardiometabolic diseases, including obesity, diabetes, and heart disease. Exercise has the potential to be an effective therapeutic to counteract the deleterious effects of sleep disruption listed above, whereas chronic psychosocial stress may causally promote sleep disruption and cardiometabolic risk. Here, we provide a narrative review of the current evidence on the consequences of short sleep duration and poor sleep quality on substrate metabolism, circulating appetite hormones, hunger and satiety, and weight gain. Secondly, we provide a brief overview of chronic psychosocial stress and its impact on sleep and metabolic health. Finally, we summarise the current evidence regarding the ability of exercise to counteract the adverse metabolic health effects of sleep disruption. Throughout the review, we highlight areas where additional interrogation and future exploration are necessary.

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

BackgroundThere is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators.MethodsMaternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age.ResultsIn mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models.ConclusionsThe results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

Detections of organophosphate and pyrethroid insecticide metabolites in urine and sweat obtained from women during infrared sauna and exercise: A pilot crossover study.

Synthetic pesticides such as organophosphates and pyrethroids are commonly used worldwide yet the metabolic and long-term human health effects of these environmental exposures are unclear. Urinary detections of metabolites involving both classes of insecticides have been documented in various global populations. However, reports documenting similar detections in human sweat are sparse. In this study, the concentrations of four insecticide metabolites were measured using liquid chromatography coupled with tandem mass spectrometry in repeated sweat and urine collections (n=85) from 10 women undergoing three interventions (control, infrared sauna and indoor bicycling) within a single-blinded randomised crossover trial. The Friedman test with post-hoc two-way analysis of variance, the related-samples Wilcoxon signed rank test and the Spearman's rank-order correlation test were used to analyse the results. Organophosphate metabolites were detected in 84.6% (22/26) and pyrethroids in 26.9% (7/26) of the collected sweat samples (pooled per individual, per intervention). Urinary concentrations of three of the four metabolites marginally increased after infrared sauna bathing: 3,5,6-trichloro-2-pyridinol (z=2.395, p=0.017); 3-phenoxybenzoic acid (z=2.599, p=0.009); and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (z=2.090, p=0.037). Urinary 3-phenoxybenzoic acid also increased after exercise (z=2.073, p=0.038) and demonstrated the most temporal variability (days to weeks) of any of the urinary metabolites. Definitive sweat/urine correlations were not demonstrated. These results indicate metabolites from organophosphate and pyrethroid pesticides can be detected in human sweat and this raises intriguing questions about perspiration and its role in the metabolism and excretion of synthetic pesticides.

The Role of Nutrition in Mitigating the Effects of COVID-19 from Infection through PASC.

The expansive and rapid spread of the SARS-CoV-2 virus has resulted in a global pandemic of COVID-19 infection and disease. Though initially perceived to be acute in nature, many patients report persistent and recurrent symptoms beyond the infectious period. Emerging as a new epidemic, "long-COVID", or post-acute sequelae of coronavirus disease (PASC), has substantially altered the lives of millions of people globally. Symptoms of both COVID-19 and PASC are individual, but share commonality to established respiratory viruses, which include but are not limited to chest pain, shortness of breath, fatigue, along with adverse metabolic and pulmonary health effects. Nutrition plays a critical role in immune function and metabolic health and thus is implicated in reducing risk or severity of symptoms for both COVID-19 and PASC. However, despite the impact of nutrition on these key physiological functions related to COVID-19 and PASC, the precise role of nutrition in COVID-19 infection and PASC onset or severity remains to be elucidated. This narrative review will discuss established and emerging nutrition approaches that may play a role in COVID-19 and PASC, with references to the established nutrition and clinical practice guidelines that should remain the primary resources for patients and practitioners.

Metformin therapy in pediatric type 2 diabetes mellitus and its comorbidities: A review.

Type 2 diabetes (T2D) rates in children and adolescents are rising globally. T2D is a complex and aggressive disease in children with several comorbidities, high treatment failure rates, and insulin needs within a few years from diagnosis. While myriads of pharmacotherapies are licensed to treat adults with T2D, treatments accessible to children and adolescents have been limited until recently. Metformin is an old drug with multiple beneficial metabolic health effects beyond glycemic control. This review discusses Metformin's origins, its mechanisms of action, and evidence for its use in the pediatric population to treat and prevent T2D. We also explore the evidence for its use as an obesity therapy, which is the primary driver of T2D, and T2D-driven comorbidities. While emerging therapies create new horizons for managing pediatric T2D, Metformin remains an inexpensive and safe part of the treatment plans of many T2D children globally for its beneficial metabolic effects.

ODP009 Obesity-related Conditions in Adults with Overweight and Obesity in the United States: A Cluster Analysis

Abstract Background Obesity is a heterogeneous chronic condition that has varying metabolic, structural, inflammatory, degenerative, neoplastic and psychological health effects. We aimed to identify common patterns of obesity-related conditions in a nationally representative sample. Methods Respondents age ≥18y with body mass index (BMI) &amp;gt;25 kg/m2 in NHANES 2017-2018 were clustered based on key obesity-related conditions including type 2 diabetes (T2D), dyslipidemia, hypertension (HTN), cardiovascular disease (CVD), chronic kidney disease (CKD), osteoarthritis, physical limitation (PL), cancer, depression, and anxiety. Hierarchical adaptive means clustering was employed with NHANES survey weights. An optimal number of clusters was chosen with the "elbow method." Patient characteristics were compared across clusters. Clusters were characterized by conditions with a ≥ 50% prevalence in descending order. Results Six clusters were identified among 3,084 respondents. Cluster 1 (15.8% of the respondents; mean age: 34.9y; female: 53.5%; mean BMI: 30.8) had no obesity-related conditions. Cluster 2 (27.7%; 47.3; 42.7%; 32.5) was dominated by HTN. Cluster 3 (9.9%; 58. 0; 44.1%; 33. 0) was dominated by CKD and HTN. Cluster 4 (13.2%; 55.1; 68. 0%; 33.7) was dominated by depression, HTN, PL and dyslipidemia. Cluster 5 (23.7%; 59.4; 50.7%; 32.6) was dominated by HTN, PL, CVD and dyslipidemia. Cluster 6 (10.1%; 67.8; 45. 0%; 34.3) was dominated by HTN, dyslipidemia, T2D, PL, and CVD. Clusters 4 and 6 incurred the highest healthcare use. Conclusions Adults with overweight and obesity in the US have distinct patterns of obesity-related conditions, the burden of which generally increased with obesity severity and age. Presentation: No date and time listed