Obesity Research Articles

Composition of gut microbiota in obese and normal-weight Uygur adults and its association with adipocyte-related factors

Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae_UCG_014, Coprococcus_2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation.

A One-Week Elderberry Juice Intervention Augments the Fecal Microbiota and Suggests Improvement in Glucose Tolerance and Fat Oxidation in a Randomized Controlled Trial.

Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m2) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium, Ruminococcaceae, and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Correlation between Fear of fall, Physical Function And Psychological Health Among Obese And Non-Obese Older Adults Diagnosed With Knee Osteoarthritis

Correlation between Fear of fall, Physical Function And Psychological Health Among Obese And Non-Obese Older Adults Diagnosed With Knee Osteoarthritis

The risks and benefits of managing obesity in older adults.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. This review discusses weight loss considerations in overweight and obese older adults. Current US guidelines do not address weight loss in older adults. Waist circumference rather than body mass index (BMI) may be a more accurate assessment tool for obesity in older adults. Weight loss interventions are not recommended in overweight older adults due to the decreased mortality in this population (known as the "obesity paradox"). While weight loss in obese older adults may be beneficial, it is not without risks. The greatest risks include loss of muscle mass, decline in bone mineral density, and development of sarcopenic obesity. Weight loss interventions may be considered in older adults with a BMI of greater than 30kg/m2 who have metabolic derangements, cardiovascular disease, and/or functional impairments after carefully weighing the risks against the benefits of weight loss and the impact of interventions on the patient's quality of life. Medicare provides limited benefits for weight loss interventions. In older adults, there is no consensus on which lifestyle interventions are best for weight loss and there is a paucity of data on the use of weight loss medications. Careful consideration should be given before utilizing medications for weight loss in older adults given the enhanced adverse effect profiles, interactions, contraindications, and costs. Weight loss in older adults should be approached differently from that in the general adult population. More data are needed on the efficacy and safety of weight loss medications in older adults.

The impact of 3 different dietary interventions on overweight or obese adults: A network meta-analysis.

This network meta-analysis aims to investigate and compare the effectiveness of 3 dietary interventions - Mediterranean, ketogenic, and low-fat diet - on overweight and obese adults, with a comparison to traditional low-calorie diet. A systematic review was conducted in both Chinese and English databases, including the China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), SinoMed, PubMed, Web of Science, Cochrane Library and Embase to identify relevant randomized controlled trials (RCTs) up to January 31, 2024. Two researchers independently screened and extracted data from the identified literature. The quality of these studies was assessed using the Cochrane bias risk assessment tool. A random-effects network meta-analysis was performed using Review Manager 5.4.1 and Stata 16.0 software. A total of 17 randomized controlled trials involving 5802 subjects were included in this study. The network meta-analysis revealed a descending order of effectiveness for reducing body weight (BW), body mass index (BMI), and waist circumference (WC): ketogenic diet > low-fat diet > low-calorie diet > Mediterranean diet. The ketogenic diet was identified as the most effective intervention for reducing BW, BMI, and WC in the studied dietary comparisons. It consistently showed superior outcomes, ranking highest in effectiveness among the 4 evaluated dietary approaches. Nevertheless, additional high-quality randomized controlled trials are necessary to validate these findings.

Is Fasting Superior to Continuous Caloric Restriction for Weight Loss and Metabolic Outcomes in Obese Adults? A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

fasting-based strategies (FBS) and continuous caloric restriction (CCR) are popular methods for weight loss and improving metabolic health. FBS alternates between eating and fasting periods, while CCR reduces daily calorie intake consistently. Both aim to create a calorie deficit, but it is still uncertain as to which is more effective for short- and long-term weight and metabolic outcomes. this systematic review and meta-analysis aimed to compare the effectiveness of FBS and CCR on these parameters in obese adults. after screening 342 articles, 10 randomized controlled trials (RCTs) with 623 participants were included. both interventions led to weight loss, with a reduction of 5.5 to 6.5 kg observed at the six-month mark. However, the results showed that FBS led to slightly greater short-term reductions in body weight (-0.94 kg, p = 0.004) and fat mass (-1.08 kg, p = 0.0001) compared to CCR, although these differences are not clinically significant. Both interventions had similar effects on lean mass, waist and hip circumference, blood pressure, lipid profiles, and glucose metabolism. However, FBS improved insulin sensitivity, with significant reductions in fasting insulin (-7.46 pmol/L, p = 0.02) and HOMA-IR (-0.14, p = 0.02). despite these short-term benefits, FBS did not show superior long-term outcomes compared to CCR. Both strategies are effective for weight management, but more research is needed to explore the long-term clinical relevance of FBS in obese populations.

Role of Planetary Health Diet in the association between genetic susceptibility to obesity and anthropometric measures in adults.

The roles of overall diet quality in linking genetic background with anthropometric measures are unclear, particularly regarding the recently developed Planetary Health Diet (PHD). This study aims to determine if the PHD mediates or moderates the relationship between genetic susceptibility to obesity and anthropometric measures. The study involved 2942 individuals from a Finnish population-based cohort (54% women, mean age 53 (SD ± 13) years). Habitual diet was assessed using a validated 130-item food frequency questionnaire, and the PHD Score (total score range 0-13 points) was adapted for Finnish food culture to evaluate diet quality. Genetic susceptibility to obesity was evaluated with a polygenic risk score (PRS) based on one million single nucleotide polymorphisms associated with body mass index (BMI). Baseline anthropometrics included weight, height, waist circumference (WC), and body fat percentage, with changes in these measures tracked over 7 years. A five-step multiple linear regression model and multivariable logistic regression with interaction terms were used to assess the mediating and moderating effects of the PHD. These analyses were also replicated in another Finnish cohort study (2 834 participants). PRS for BMI was positively associated with baseline BMI and changes in anthropometric measures, except waist circumference (p = 0.12). Significant associations were observed for baseline BMI and WC (p < 0.001), changes in BMI and WC (p = 0.01), and body fat percentage change (p = 0.05). However, the PHD (average score 3.8 points) did not mediate or moderate these relationships. These findings were consistent in the replication cohort. Diet quality assessed with the PHD did not mediate or moderate the associations between genetic susceptibility to obesity and anthropometric measures. This lack of effect may be partly due to low adherence to the PHD and the older age of participants ( > 50 years) at baseline.

Employing single-cell RNA sequencing coupled with an array of bioinformatics approaches to ascertain the shared genetic characteristics between osteoporosis and obesity.

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor (TLR) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB.

Continuous Glucose Monitor Metrics That Predict Neonatal Adiposity in Early and Later Pregnancy Are Higher in Obesity Despite Macronutrient-Controlled Eucaloric Diets.

Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14-16 weeks) and Later (26-28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat. In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63-140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA). Fifty-four women with NW (BMI: 23 kg/m2; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95-99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9-19 mg/dL) and Later (15-26 mg/dL). In OB, the Later group's 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05). Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.

Childhood maltreatment, adulthood obesity and incident type 2 diabetes: a retrospective cohort study using UK Biobank.

This study aims to explore the association of childhood maltreatment with obesity and type 2 diabetes (T2D) in adulthood, and whether obesity is a mediator of the latter. In a retrospective cohort study using UK Biobank data, participants recalled childhood maltreatment. Linear regression, logistic regression, and Cox proportional hazard models were used to investigate the associations with body mass index (BMI), obesity, and T2D, adjusted for sociodemographic factors. Decomposition analysis was used to examine the extent to which T2D excess risk was attributed to BMI. Of the 153,601 participants who completed the childhood maltreatment questions, one-third reported some form of maltreatment. Prevalence of adult obesity and incidence of T2D were higher with the number of reported childhood maltreatment types. People who reported ≥3 types of childhood maltreatment were at higher risk of obesity (OR 1.55, 95% CI 1.47-1.63) and incident T2D (HR 1.65, 95% CI 1.52-1.80). Excess T2D risk among those reporting maltreatment could be reduced by 39% if their BMI was comparable to participants who had not been maltreated, assuming causality. People who recalled maltreatment in childhood are at higher risk of T2D in adulthood, partly due to obesity.

Effects of Specially Designed Energy-Restricted Diet on Anthropometric Parameters and Cardiometabolic Risk in Overweight and Obese Adults: Pilot Study.

This study examined the effects of a specially designed energy-restricted diet with alternate carbohydrate intake on body composition and cardiometabolic risk factors in overweight and obese adults. The aim was to assess whether the intervention could lead to significant weight loss, improve body composition, and reduce cardiometabolic risks. Sixty-five participants (34 women, 31 men) with an average BMI of 31.8 ± 9.1 kg/m2 (women) and 34.1 ± 6.4 kg/m2 (men) participated in a 14-week intervention. The diet included different days of carbohydrate intake and a 20% reduction in total daily energy consumption. Anthropometric measurements and biochemical parameters, including predictive indices of cardiometabolic risk, were determined at baseline and after the intervention. The intervention resulted in a significant reduction in body weight (mean weight loss of 17%, p < 0.001), with 64.6% of participants achieving a weight loss of at least 10%. Muscle mass as a percentage of total body weight increased. Cardiometabolic improvements were observed in fasting blood glucose (from 5.4 to 4.9 mmol/L, p < 0.001) and LDL cholesterol (from 3.38 to 2.81 mmol/L, p < 0.001). Gender-specific differences were found, particularly in HDL-C, which decreased significantly in women (p = 0.013), while there was a non-significant increase in men. Cardiometabolic indices, including the Visceral Adiposity Index (VAI) and the Cardiometabolic Index (CMI), also improved significantly. The alternate carbohydrate diet improved body composition, cardiometabolic health, and treatment adherence through metabolic flexibility. However, the short duration of this study and the lack of a control group suggest that further research is needed to assess long-term sustainability.

DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort.

Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

OBESIDADE INFANTIL: FISIOPATOLOGIA E CONSEQUÊNCIAS NA VIDA ADULTA

Introduction: excess weight is due to the abnormally high accumulation of adipose tissue, which results from a caloric surplus through the influence of multiple causal factors, highlighting a sedentary lifestyle and harmful dietary habits. Methodology: study consists of an integrative review of scientific literature, based on previous studies and literary sources, with the bibliographic survey carried out on the Scientific Electronic Library Online portal. Discussion: addresses aspects of childhood obesity, including etiology, clinical picture and diagnosis; with an emphasis on pathophysiology, impacts of childhood obesity in adulthood and management of the disease. Final considerations: considered one of the main epidemics of the 21st century; In this context, childhood obesity stands out, responsible for promoting changes in adipocyte hyperplasia and generating a harmful inheritance for the individual, associated with the repercussions that clinical intervention has in order to prevent and treat excess weight and its respective comorbidities.

Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium breve BBr60 (BBr60) group or a placebo group. Both groups received diet guidance and took either BBr60 (1 × 1010 CFU/day) or a placebo for 12 weeks. Researchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pretreatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulate BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

Trend analysis, gender-specific patterns, and age dynamics of childhood and adolescent obesity: insights from the Tehran lipid and glucose study

BackgroundChildhood and adolescent obesity pose significant challenges to global health, with escalating prevalence and associated short- and long-term health consequences. This longitudinal study leveraged data from the Tehran Lipid and Glucose Study (TLGS) to investigate the trends of obesity among Tehranian children and adolescents over a 21-year period.MethodsUtilizing data from TLGS phases I to VII (1999–2021), we included 3845 participants aged 3–18 years at the beginning of phase I. Anthropometric measures, including height and weight, were collected, and body mass index (BMI) was calculated. Childhood obesity (2–19 years) was defined as BMI-for-age > 2SD based on World Health Organization (WHO) standards, and adult obesity was defined as BMI ≥ 30. Descriptive statistics, trend analysis, prevalence calculations, odds ratios, and interaction analyses were employed for data interpretation.ResultsThe mean BMI increased from 18.46 ± 4.37 kg/m² at Phase I to 26.36 ± 5.03 kg/m² at Phase VII. Boys exhibited a greater increase in BMI than girls, and age at study entry influenced BMI trajectories. The prevalence of obesity rose from 6.4% at Phase I to 21.5% at Phase VII, with a more pronounced increase in boys. Odds ratios for obesity steadily increased across phases, indicating a growing risk. Interaction analyses revealed age-specific dynamics, with older participants demonstrating lower odds ratios initially but higher odds ratios in later phases.ConclusionOur study shows a worrisome increase in childhood obesity among Tehranian children and adolescents over 21 years. Sex- and age-specific trends emphasize the necessity for targeted interventions, informing policymakers, healthcare practitioners, and educators regarding public health strategies and interventions against the obesity epidemic.

Effects of plant-based diets combined with exercise training on leptin and adiponectin levels in adults with or without chronic diseases: a systematic review and meta-analysis of clinical studies.

The effects of exercise training combined with plant-based diets (PBD) on leptin and adiponectin levels have been studied. However, little is known regarding the impact of exercise training combined with PBD on leptin and adiponectin levels in adults with or without chronic diseases. PubMed, Web of Science, and Scopus were searched to identify original articles, published until May 2024, to assess the effects of exercise training combined with PBD on leptin and adiponectin levels in adults with or without chronic diseases. Standardized mean differences (SMD) and 95% confidence intervals were calculated using random models. Nine studies comprising 960 participants with overweight and obesity were included in the current meta-analysis. Exercise training combined with PBD reduced leptin [SMD = -0.33 (95% CI: -0.62 to -0.04); p = 0.025] while increasing adiponectin [SMD = 0.93 (95% CI: 0.12 to 1.74); p = 0.024] levels. Exercise training combined with PBD is suggested as a non-invasive intervention for reducing leptin while increasing adiponectin levels to control body mass and other disorders related to obesity in adults.

The Relationship Between Anthropometric Indices of Obesity and Sleep Disturbances in Young Adults

The Relationship Between Anthropometric Indices of Obesity and Sleep Disturbances in Young Adults

How Would You Manage This Patient With Obesity? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?

Age-Related Changes in Insulin Resistance and Muscle Mass: Clinical Implications in Obese Older Adults.

The older segment of the global population is increasing at a rapid pace. Advancements in public health and modern medicine lengthened life expectancy and reduced the burden of disease in communities worldwide. Concurrent with this demographic change is the rise in overweight people and obesity, which is evident in all age groups. There is also an aging-related reduction in muscle mass and function, or sarcopenia, that is exacerbated by sedentary lifestyle and poor nutrition. The coexistence of muscle loss and elevated body mass index, termed "sarcopenic obesity", has particularly deleterious consequences in older individuals. Worsening insulin resistance and a proinflammatory state operate at the pathophysiologic level and lead to adverse health outcomes such as a proclivity to cardiovascular disease, type 2 diabetes, and even cognitive dysfunction. Although the concept of sarcopenic obesity as a disease construct is being increasingly recognized, a clearer understanding is warranted in order to define its components and health impact. Research is needed at the molecular-cellular level to tie together derangements in insulin action, cytokines, myokines, and endothelial dysfunction with clinical outcomes. Lifestyle modifications as well as targeted nonpharmacologic approaches, such as supplements and antioxidants, appear to have a promising role in reducing the chronic burden of this emerging disorder. Breakthroughs in drug therapies that retard or even reverse the underlying dynamics of sarcopenia and obesity in older persons are being actively explored.

7858 Increasing Severity of Growth Hormone Deficiency is Associated with Lower Vertebral Strength

Abstract Disclosure: R. Boutin: None. M. Haines: None. R. Shahid: None. C. Mark: None. C. Gill: None. M. Bredella: None. K.K. Miller: Other; Self; Pfizer, Inc. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Grant Recipient; Self; Lumos Pharma, Perspectum Ltd. Research Investigator; Self; Recordati, Novo Nordisk. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. Objective: Growth hormone (GH) stimulates osteoblast differentiation, while insulin-like growth factor-1 (IGF-1) stimulates osteoblast proliferation and bone formation. Retrospective studies have demonstrated a 2-to-3-fold increased fracture risk in adults with GH deficiency (GHD) due to organic hypothalamic or pituitary disease, particularly at vertebral sites. Adults with overweight/obesity produce relatively less GH than lean individuals, and serum IGF-1 levels are associated positively with BMD in adults with obesity. Yet, no published studies have examined the relationship between degree of GHD across these groups and vertebral strength, an understudied measure of bone quality in part because HR-pQCT cannot image this skeletal site. We hypothesized that there would be an inverse association between degree of GHD and vertebral strength, independent of age and BMI. Methods: Cross-sectional study of 134 estrogen-replete (with regular menses or taking estrogen) women: 16 with GHD secondary to hypopituitarism (HP, severe GHD), 91 with obesity (OB) without a hypothalamic/pituitary disorder (relative GHD), and 37 lean controls (LC) without a hypothalamic/pituitary disorder (normal GH production). Peak-stimulated GH was assessed by GHRH-arginine testing. CT imaging at the L4 vertebra was performed to determine vertebral cross-sectional area and total integrated volumetric bone mineral density (Int.vBMD), from which estimates of vertebral strength were calculated. Results: Mean age [44±9 (mean±SD) (HP) vs. 35±7 (OB) vs. 30±7 (LC) y, p&amp;lt;0.005] and BMI [30±6 (HP) vs. 34±6 (OB) vs. 22±2 (LC) kg/m2, p&amp;lt;0.004] differed between all groups. As expected, peak-stimulated GH was highest in LC (28.3 ± 9.5 ng/mL) followed by OB (12.4 ± 8.9 ng/mL) and HP (2.4 ± 1.7 ng/mL), p&amp;lt;0.0001. IGF-1 Z-scores were higher in LC (0.0 ± 0.6) and OB (0.0 ± 0.7) vs. HP (-1.4 ± 0.7), p&amp;lt;0.0001. Int.vBMD and vertebral strength were higher in LC and OB vs. HP [Int.vBMD (g/cm3) LC 0.21±0.04 and OB 0.21±0.04 vs. HP 0.16±0.03, and vertebral strength (N) LC 4540±850 and 4743±91 vs. HP 3542±651, both p&amp;lt;0.0001], which remained significant when adjusted for age and BMI (p≤0.01). Peak-stimulated GH and IGF-1 Z-scores were positively associated with vertebral strength (GH R=0.33, p=0.003 and IGF-1 Z-score R=0.41, p&amp;lt;0.0001) and Int.vBMD (GH R=0.46, p&amp;lt;0.0001 and IGF-1 Z-score R=0.40, p&amp;lt;0.0001), which remained significant when adjusted for age and BMI. Among the subset of patients without organic pituitary disease (LC and OB only), IGF-1 Z-scores remained positively associated with vertebral strength (R=0.24, p&amp;lt;0.03) and Int.vBMD (R=0.22, p&amp;lt;0.05). Conclusions: These findings suggest that severe GHD is associated with impaired vertebral volumetric bone density and strength. Moreover, the relative GHD of obesity may contribute to lower vertebral bone density and strength in otherwise healthy adults with overweight/obesity. Presentation: 6/3/2024