Pediatric Obesity

An inexpensive measure of obesity in children and adolescents that could replace body mass index (BMI) has been identified in a new study as waist circumference-to-height ratio. This measure detected excess fat mass and distinguished fat mass from muscle mass in children and adolescents more accurately than BMI. An inexpensive measure of obesity in children and adolescents that could replace body mass index (BMI) has been identified in a new study as waist circumference-to-height ratio. This measure detected excess fat mass and distinguished fat mass from muscle mass in children and adolescents more accurately than BMI. The study was conducted in collaboration between the University of Bristol in the UK, the University of Exeter in the UK, and the University of Eastern Finland, and the results were published in Pediatric Research. The prevalence of childhood and adolescent obesity has reached an epidemic proportion and is affecting nearly 1 in 4 children in the current decade. Unfortunately, obesity in the young population has been associated with cardiovascular, metabolic, neurological, musculoskeletal diseases and premature death in adulthood. Accurately detecting overweight and obesity in children is critical to initiating timely interventions. For nearly a generation, weight-to-height ratio charts and BMI for age and sex have been used to diagnose children with obesity. However, these surrogate assessment tools are inaccurate in childhood and adolescence since they do not distinguish fat mass from muscle mass.For instance, two children with similar BMI might have different proportions of fat and muscle mass which makes obesity diagnosis difficult. Expensive tools such as the dual-energy Xray absorptiometry (DEXA) scan accurately measures fat and muscle content of the body, but this device is not readily available in primary health care centres. Recently, the American Academy of Pediatrics (AAP) published a clinical guideline on childhood obesity and requested urgent research on inexpensive and accurate alternative measures of obesity. Emerging studies in adults appear to suggest that waist circumference-to-height ratio predicts premature death better than BMI and could be a potential added tool to BMI measure in improving the diagnosis of obesity. However, there has been no former evaluation of how much waist circumference-to-height ratio measurements agree with DEXA-measured fat mass and muscle mass during growth from childhood to young adulthood. In addition, the threshold of waist circumference-to-height ratio needed to detect excess fat in children is not clear, hence this study. The current study is the largest and the longest follow-up DEXA-measured fat mass and muscle mass study in the world using the University of Bristol's Children of the 90s data (also known as the Avon Longitudinal Study of Parents and Children). The study included 7,237 children (51% females) aged 9 years who were followed-up until age 24 years. Their BMI and waist circumference-to-height ratio were measured at ages 9, 11, 15, 17, and 24 years. When different devices measure a variable with an exact resemblance, it is described as perfect agreement of the devices with a score of 100%. For example, two DEXA scans from different manufacturers would measure fat mass with a near-perfect agreement of 99 to 100%. Waist circumference-to-height ratio had a very high agreement of 81 -- 89% with DEXA-measured total body fat mass and trunk fat mass, but a low agreement with muscle mass (24 -- 39%). BMI had a moderate agreement with total fat mass and trunk fat mass (65 -- 72%) and muscle mass (52 -- 58%). Since BMI had a moderate agreement with DEXA-measured muscle mass, it is difficult to specify whether BMI measures excess fat or muscle mass. The optimal waist circumference-to-height ratio cut points that predicted the 95th percentile of total fat mass in males was 0.53 and 0.54 in females. This cut point detected 8 out of 10 males and 7 out of 10 females who truly had excess DEXA-measured fat. The cut point also identified 93 out of 100 males and 95 out of 100 females who truly do not have excess fat. "This study provides novel information that would be useful in updating future childhood obesity guidelines and policy statements. The average waist circumference-to-height ratio in childhood, adolescence, and young adulthood is 0.45, it does not vary with age and among individuals like BMI. Waist circumference-to-height ratio might be preferable to BMI assessment in children and adolescent clinics as an inexpensive tool for detecting excess fat. Parents should not be discouraged by the BMI or weight of their children but can inexpensively confirm whether the weight is due to increase in excess fat by examining their kid's waist circumference-to-height ratio," says Andrew Agbaje, an award-winning physician and pediatric clinical epidemiologist at the University of Eastern Finland. Dr Agbaje's research group (urFIT-child) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research, Ida Montin Foundation, Eino Räsänen Fund, Matti and Vappu Maukonen Fund, Foundation for Pediatric Research, and Alfred Kordelin Foundation.

Researchers found more unique bacteria taxa in children of normal weight than in overweight or obese children. The findings suggest that BPA exposure could promote different microbial communities in normal weight children than those in children with obesity or who are overweight. A synthetic chemical called Bisphenol A, or BPA, is widely used in the production of durable plastic products including eyewear, water bottles and epoxy resins. But it's also an endocrine disruptor, which means that it can interfere with normal hormone functions in the body. Studies suggest that high levels of exposure may be detrimental to human health in a variety of ways; it may also alter the gut microbiome. But the connections aren't clear. Researchers in Spain recently studied a group of over 100 children to identify microbes that play a role in BPA exposure and degradation, with the larger goal of understanding the complicated relationship between that process and childhood obesity. In their study, published this week in mSystems, the researchers found more unique bacteria taxa in children of normal weight than in overweight or obese children. The findings suggest that BPA exposure could promote different microbial communities in normal weight children than those in children with obesity or who are overweight. "We found that the gut microbial community responds differently to BPA exposure depending on the BMI (body-mass index) of the individual," said microbiologist Margarita Aguilera, Ph.D., at the University of Granada in Spain. Aguilera is a senior author on the study. Those connections, she said, "underscore the intricate interplay between gut microbiota and potential human pathophysiology resulting from cumulative BPA exposure." Previous studies have investigated symptoms and effects associated with BPA exposure. Others have used mouse models and 16S rRNA gene sequencing, which can reveal microbes in complex mixtures of materials, like those from the gut or water. For the new study, the researchers, including Ana López-Moreno, Ph.D., who led the experimental work as part of her doctoral thesis, instead combined analyses of cultured samples with amplicon sequencing -- an approach that, to their knowledge, hasn't been used before. The results came from a study of 106 children in Spain, roughly half boys and half girls, all between the ages of 5 and 10. They had participated in the OBEMIRISK project, an effort to understand the interplay between BPA and the gut microbiome sponsored by the European Food Safety Authority. Sixty of the children were normal weight; the rest were either overweight or obese. Fecal samples from the children were exposed to several levels of BPA and allowed to incubate for 3 days. Then, the researchers used 16s rRNA sequencing and amplicon sequencing, ultimately identifying 333 BPA-resistant bacterial species. Notably, species of Clostridium and Romboutsia found in the BPA-cultured samples promoted the richness of microbiota communities. Generally, Aguilera's team noted, normal-weight children hosted a more diverse, enriched and structured network of bacteria than those found in the groups of overweight and obese children. Those results, she said, suggest that the gut microbiota in normal-weight children may be more resilient when exposed to xenobiotic substances like BPA. Knowing which microbes participate in the complex network connecting BPA, obesity and the gut microbiome, Aguilera said, could point to future interventions and policy changes that may reduce the risk of childhood obesity worldwide. In future work, she said the researchers plan to similarly investigate how exposure to other synthetic chemicals, including parabens and phthalates, may influence the composition of the gut microbiome. Her group's overarching goal, however, is to elucidate the mechanisms behind an invisible but widespread threat. "We want to raise awareness about the health risks associated with microplastics that enter our bodies, and those that circulate in the environment," Aguilera said. "It's crucial for individuals to be mindful of these concerns."

Insulin resistance (IR), a common feature of childhood obesity which affects 15 million children and adolescents, is the main driver of obesity-related metabolic complications such as Type 2 diabetes, hypertension, and premature heart disease.This study demonstrated that NLRP3 inflammasome activation was highest in obese children with the worst metabolic profile (higher serum glucose levels, a late insulin response to glucose tolerance tests, adverse serum lipid profiles, and higher oxidative stress (based on ROS levels).ZyVersa is developing Inflammasome ASC Inhibitor IC 100 which inhibits NLRP3 and other types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of damaging inflammation. WESTON, Fla., Jan. 31, 2024 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics (Nasdaq: ZVSA, or “ZyVersa”), a clinical-stage specialty biopharmaceutical company developing first-in-class drugs for treatment of renal and inflammatory diseases, highlights an article published in the peer-reviewed Journal of Translational Medicine supporting that NLRP3 activation is associated with a pathologic inflammatory response in obese children with insulin resistance and increased risk of developing metabolic complications. Inflammation and oxidative stress, which are closely related pathophysiological processes, one of which can be easily induced by the other, are key drivers for developing metabolic complications, such as type 2 diabetes and cardiovascular disease, in this population. In the paper titled, “Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance,” the authors conducted a case-controlled study of 132 children who were either lean or obese. The obese group was segmented into those with or without insulin resistance, and those with insulin resistance were segmented into those with an early and late insulin response to glucose as determined by an oral glucose tolerance test (OGTT). The researchers reported the following key findings in Children with obesity, insulin resistance, and increased risk of metabolic complications: Higher levels of NLRP3 and its effector proteins (active IL-1β, caspase-1, and gasdermin D) in peripheral blood mononuclear cells (PBMCs) and serum compared to the other groups studied, indicative of NLRP3 activation and an inflammatory response.Higher levels of uric acid versus the other groups, a well-known trigger of NLRP3 activation.Increased levels of oxidative stress and oxidative damage versus the other groups. The authors concluded, “It is insulin response to an OGTT that identifies children with obesity suffering oxidative stress, and inflammasome activation more specifically. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.” To read the article, Click Here. “Childhood obesity, which has increased more than 8-fold over the last 40 years, is an alarming health problem today due to the increased risk for developing type 2 diabetes, early heart disease, and other co-morbidities,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “The research published in the Journal of Translational Medicine points to a significant role for inflammasome-mediated inflammation and oxidative stress in development of metabolic complications in obese children. ZyVersa is developing Inflammasome ASC Inhibitor IC 100 designed to inhibit NLRP3 and other types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of inflammation, which may have therapeutic potential to alleviate metabolic complications of childhood obesity with early intervention.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. About Inflammasome ASC Inhibitor IC 100 IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. 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Corporate and IR Contact:Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641 Media ContactsTiberend Strategic Advisors, Inc.Casey McDonaldcmcdonald@tiberend.com646-577-8520 Dave Schemeliadschemelia@tiberend.com609-468-9325