bluuebunny/crossref_metadata_2025_split huggingface dataset:
204-OR: Social Vulnerability, Rurality, and Prevalence of Obesity and Inactivity in U.S. Counties, 2004–2019
Authors: VARGHESE BEN T. , LAHR BRIAN , VELLA ADRIAN , MIELKE MICHELLE , BAILEY KENT R. , DUGANI SAGAR B. 
Published: June 2024

Introduction: Obesity and inactivity increase cardiovascular risk and are more prevalent in rural counties. The objective was to evaluate the association of county social vulnerability index (SVI) with obesity and inactivity, independent of rurality.
Method: We used CDC data (2004-2019; 97.5% of 3226 US counties) on county prevalence of obesity (BMI ≥30 kg/m2) and leisure-time inactivity. CDC SVI included 4 themes (socioeconomic status, household composition & disability, minority status & language, housing type & transportation) and was scored from 0 to 1 (low to high vulnerability). We used weighted least squares regression with restricted cubic splines to model the association of SVI with obesity and inactivity (median of 2004-2019). We adjusted for sociodemographic factors and rurality and reported the partial effects of SVI with F statistics and prevalence ratios (95% CI).
Result: SVI showed strong, monotonic, and independent associations with prevalence of obesity and inactivity (both, P&lt;.001), after adjusting for sociodemographic factors and rurality. A change in SVI from the 25th to 75th percentile was associated with an 11% higher rate of obesity (1.11 [1.09-1.12]) and a 16% higher rate of inactivity (1.16 [1.14-1.18]). (Figure)
Conclusion: US counties with higher SVI have higher prevalence of obesity and inactivity, independent of rurality. SVI may identify counties for targeted intervention.

Disclosure
B.T. Varghese: None. B. Lahr: None. A. Vella: Research Support; Novo Nordisk. Consultant; Hanmi Pharm. Co., Ltd., Crinetics Pharmaceuticals, Inc. Advisory Panel; Rezolute, Inc. M. Mielke: Consultant; Biogen. Advisory Panel; Eisai Inc., Merck & Co., Inc. Consultant; Eli Lilly and Company. Advisory Panel; Roche Diagnostics. K.R. Bailey: None. S.B. Dugani: None.

Funding
National Institutes of Health (K23 MD106230)
2044-LB: IGF2 Deficiency Promotes Obesity by Inhibiting Testosterone Synthesis through Suppression of Autophagy
Authors: LIN XIHUA , ZHOU CAIPING , WU FANG , GUI WEIWEI 
Published: June 2024

Objective: This study aims to investigate the role of Insulin-like Growth Factor 2 (IGF2) deficiency in promoting obesity through suppressed testosterone synthesis in Leydig cells by modulating autophagy flux.
Methods: Conditional hepatocyte-specific Igf2 knockout mice (Igf2 ΔHep) were generated. Body weight gain, serum testosterone, and glucose-lipid metabolic indicators were compared between Igf2 ΔHep and control mice. Transcriptomic sequencing was conducted on liver samples, and a combined analysis was done on publicly available single-cell sequencing data from testicular tissues. Autophagy levels and autolysosomes changes in Leydig cells were measured via autophagy marker protein LC3 and transmission electron microscopy (TEM). Key testosterone synthesis enzymes HSD17B and CYP17A1 expressions were quantified, followed by assessing cholesterol uptake using the BODIPY-cholesterol probe.
Results: Hepatocyte-specific Igf2 deletion mice exhibited accelerated weight gain compared to controls, coupled with significantly lower serum testosterone levels. Single-cell transcriptomics and immunofluorescence confirmed predominant expression of IGF2 and IGF2R in Leydig cells within the testes. Transcriptomic analysis disclosed downregulated genes in cholesterol metabolism and steroidogenesis pathways in Igf2 ΔHep mice. Immunofluorescence assays verified reduced expression of LC3 and TEM revealed a significant decrease in autolysosomes in Leydig cells of Igf2 ΔHep mice. Fluorescent co-staining and BODIPY-cholesterol assays indicated downregulated expression of testosterone synthesis enzymes HSD17B/CYP17A1 and decreased cholesterol uptake in IGF2-deficient mice.
Conclusion: This research demonstrated that IGF2 deficiency suppresses testosterone synthesis by regulating autophagy in Leydig cells, affecting cholesterol uptake and utilization, thereby potentially lowering testosterone levels and increasing obesity risk in males.

Disclosure
W. Gui: None.

Funding
National Natural Science Foundation of China (82370846)
2045-LB: Target-Derived Factors Decrease Sympathetic Innervation of Brown Adipose Tissue in a Critical Period of Development
Authors: FOHN ALEXIS , NERI DANIELE , RAMOS-LOBO ANGELA , LEDUC CHARLES A. , ODLE ANGELA , ZELTSER LORI M. 
Published: June 2024

A wide range of developmental exposures can influence the establishment of sympathetic nervous system (SNS) tone onto metabolically relevant organs, but little is known about the underlying mechanism. Rearing mice at an ambient temperature of 30°C vs. 22°C from birth to 8 weeks of life programs lasting effects on SNS tone onto brown adipose tissue (BAT) and the capacity to respond to chronic cold challenges. We used this system to identify a critical period of development and potential molecular mediators of these effects. Utilizing cholera toxin B retrograde tracing we visualized sympathetic neurons in the stellate ganglion innervating BAT (SGBAT). By comparing the number of SGBAT neurons in mice reared at 30°C vs. 22°C across the first 8 weeks of life, we defined a time window when rearing at 30°C is associated with a marked decrease in innervation. Analyses of transcriptional profiles from bulk RNA-sequencing of BAT during this critical period revealed several signaling molecules that are differentially expressed at 30°C vs. 22°C. Complementary gain- and loss-of-function studies are underway to test the contribution of these candidate factors to the establishment of BAT SNS tone during development. Mechanisms identified here will provide a framework for analogous studies in other organs that are also implicated in developmental programming of health and disease.

Disclosure
A. Fohn: None. D. Neri: None. A. Ramos-Lobo: None. C.A. LeDuc: None. A. Odle: None. L.M. Zeltser: None.

Funding
National Institutes of Health (R01-DK125094)
206-OR: Assessing Connection to Outpatient Care among Patients Screening Positive for Previously Undiagnosed Diabetes in the Emergency Department
Authors: ANNEM VIDHYASAI , FAN CATHERINE , GANSUKH ENKHJIN , JOY QUINN , KAO DENIKA , KULIS NATALIA , NUNEZ CHRISTOPHER , TING KAILA S. , UPPAL DIVYA W. , REDDY HARITA , KOZIATEK CHRISTIAN A. , LEE DAVID C. 
Published: June 2024

Introduction & Objective: Patients with frequent emergency department (ED) use often have poor connection to primary care, which limits their access to the preventive screening necessary to diagnose diabetes early. Our objective was to assess how frequently patients connected with outpatient care after a new diagnosis of diabetes through an ED-based screening program.
Methods: We performed a survey of all ED patients with newly diagnosed diabetes in 2022 at our health system, which now screens all ED patients aged 35 to 70 years old with a BMI ≥ 25 that do not have a prior history of diabetes in our records. HbA1c tests are added among those already receiving blood work as part of their care. We contacted each of these patients at least 6 months after they had been screened to participate in a phone-based survey about awareness of their new diagnosis, follow-up for outpatient care, and changes in health behaviors.
Results: In 2022, we screened 9,897 ED patients and found that 615 (6.2%) had a HbA1c ≥ 6.5%. After 3 rounds of phone calls, we successfully surveyed 307 for a response rate of 50%. We found that 44% of these patients had a pre-existing history of diabetes not reflected in our health records when they were screened. Analyzing the 171 ED patients with newly diagnosed with diabetes that were successfully surveyed, we found that 79% met with an outpatient provider after screening positive for diabetes, however, only 46% remembered being diagnosed. Of those with a new diagnosis, 65% reported improving their diet, 35% reported exercising more, and 52% reported starting medications for diabetes.
Conclusion: Connection to outpatient care after a new diagnosis of diabetes in the ED was more robust than anticipated, at least among those successfully surveyed. However, we identified key gaps: many patients did not remember their diagnosis, some reported barriers to outpatient care, and several patients were not started any medications despite a high HbA1c.

Disclosure
V. Annem: None. C. Fan: None. E. Gansukh: None. Q. Joy: None. D. Kao: None. N. Kulis: None. C. Nunez: None. K.S. Ting: None. D.W. Uppal: None. H. Reddy: None. C.A. Koziatek: None. D.C. Lee: None.

Funding
National Institutes of Diabetes and Digestive and Kidney Diseases (R01DK134668)
2062-LB: Disparity in Glucose Metabolic Regulation between Sleeve Gastrectomy and Gastroplasty
Authors: MOKADEM MOHAMAD 
Published: June 2024

Sleeve gastrectomy (SG) and Endoscopic gastroplasty, are 2 effective weight loss interventions. This study assessed the impact of these interventions on weight loss, glucose homeostasis, and behavioral and hormonal parameters in mice. Both SG and gastroplasty induced significant weight loss, with SG showing lower food intake and improved feeding efficiency (Fig1). SG also showed better glucose and insulin tolerance, lower liver triglyceride levels, and reduced agouti-related protein levels compared to gastroplasty. Despite comparable weight reduction, SG demonstrated additional molecular improvements, suggesting potential for non-invasive interventions to replicate the benefits of invasive procedures (Fig2). This study highlights the potential of less invasive procedures as alternatives for treating severe obesity.

Disclosure
M. Mokadem: None.

Funding
VA Merit Award (I01 BX004774)
2066-LB: Potential to Optimize Weight Loss with Enobosarm—Meta-analysis of Body Composition from Three Randomized Clinical Trials Support the Ability of Enobosarm to Preserve Muscle while Reducing Fat
Authors: CRAWFORD JEFFREY , DOBS ADRIAN S. , EVANS WILLIAM J. , PRADO CARLA , RODRIGUEZ DOMINGO , SHALEV ITAY , GARY BARNETTE K. , STEINER MITCHELL 
Published: June 2024

Background: Enobosarm, a novel oral selective androgen receptor modulator, combined with a GLP-1 receptor agonist (RA) may prevent muscle loss, while preferentially reducing fat resulting in a higher quality weight loss. A meta-analysis was conducted of three randomized clinical studies of enobosarm involving older men, postmenopausal women, and older patients who have muscle loss due to advanced cancer. Loss of appetite occurs with advanced cancer inducing a starvation state similar to GLP-1 RA therapy.
Methods: Meta-analysis was conducted of 3 randomized clinical trials evaluating enobosarm 3mg q day versus placebo and who had a Day 84 DXA scan to assess body composition: Phase 2 study in older males (&gt;60 yo) and postmenopausal women (n=48), Phase 2 study in patients with muscle wasting because of advanced cancer (n=61), and Phase 3 study in patients with advanced lung cancer (n=258).
Results: At Day 84, DXA scan showed an absolute increase in lean mass of 1.5 kg in enobosarm treated vs placebo (p=0.00004) and % change in lean mass of a 4.04 % in enobosarm vs placebo (p=0.00007). Absolute decrease in fat mass was 0.758 kg in enobosarm treated vs placebo (p=0.015) and % change in fat mass was a loss -4.04 % in enobosarm vs placebo (p=0.006). Enobosarm was generally well tolerated with no increase in gastrointestinal side effects.
Conclusion: In meta-analysis of 367 older men, postmenopausal women, and older patients with muscle loss from advanced cancer, enobosarm therapy resulted in reductions in fat mass while preserving lean mass. Meta-analysis supports the potential for enobosarm when combined with a GLP-1 RA may preserve muscle, while preferentially reducing fat resulting in a higher quality weight loss in overweight and obese patients. A Phase 2b randomized controlled trial is currently underway to evaluate enobosarm in older patients receiving a GLP-1 RA for weight loss.

Disclosure
J. Crawford: Advisory Panel; Pfizer Inc. Research Support; Pfizer Inc., AstraZeneca, helsinn. Advisory Panel; BioAtla. Consultant; Actimed. Advisory Panel; G1 Therapeutics, Enzychem. Consultant; Faraday. Advisory Panel; Jazz. A.S. Dobs: Speaker's Bureau; Halozyme. W.J. Evans: None. C. Prado: Speaker's Bureau; Abbott Nutrition, Nestlé Health Science, Nutricia, Amra medical. Advisory Panel; Pfizer Inc. D. Rodriguez: Employee; Veru. I. Shalev: Employee; Veru. K. Barnette: None. M. Steiner: Stock/Shareholder; Veru, Inc.
2067-LB: Pooled Safety Analysis of Enobosarm from Phase 2 and Phase 3 Placebo-Controlled Clinical Trials
Authors: CRAWFORD JEFFREY , DOBS ADRIAN S. , EVANS WILLIAM J. , PRADO CARLA , RODRIGUEZ DOMINGO , SHALEV ITAY , GARY BARNETTE K. , STEINER MITCHELL 
Published: June 2024

Background: Enobosarm is a novel oral selective androgen receptor modulator shown to increase lean mass and decrease fat mass. Enobosarm may benefit patients on GLP-1 RA for weight loss by preserving muscle while augmenting fat loss. A pooled analysis was conducted from 4 randomized clinical trials (RCT) to evaluate the safety profile of enobosarm.
Methods: The pooled safety analysis of enobosarm (3mg) included: Ph2 study in older males (&gt;60 yo) and postmenopausal women (n=48), two Ph3 studies in patients with advanced lung cancer (n=651), and a Ph2 stress urinary incontinence study (n=328).
Results: TEAEs observed with enobosarm were comparable to the placebo group. Most common AEs for enobosarm were nausea (26.6% vs 26.0% in placebo), anemia (25.6% vs 23.9% in placebo), and vomiting (14.8% vs 14.6% in placebo), which were similar to the placebo groups. Notably, there was no increase in gastrointestinal AEs and no evidence of drug induced liver injury with enobosarm compared to placebo treatment. The incidence of deep vein thrombosis was higher (3.3%) in placebo compared to the enobosarm group (1%).
Conclusion: In pooled analysis of 1027 older men, postmenopausal women, and older patients with muscle loss from advanced cancer, enobosarm was well tolerated with an AE profile comparable to the control patients. A Ph2b randomized trial is underway to evaluate enobosarm in older patients on a GLP-1 RA for weight loss.

Disclosure
J. Crawford: Advisory Panel; Pfizer Inc. Research Support; Pfizer Inc., AstraZeneca, helsinn. Advisory Panel; BioAtla. Consultant; Actimed. Advisory Panel; G1 Therapeutics, Enzychem. Consultant; Faraday. Advisory Panel; Jazz. A.S. Dobs: Speaker's Bureau; Halozyme. W.J. Evans: None. C. Prado: Speaker's Bureau; Abbott Nutrition, Nestlé Health Science, Nutricia, Amra medical. Advisory Panel; Pfizer Inc. D. Rodriguez: Employee; Veru. I. Shalev: Employee; Veru. K. Barnette: None. M. Steiner: Stock/Shareholder; Veru, Inc.
2070-LB: Enhancing Metabolic Health in Obesity via Testosterone Replacement—Insights from a Meta-analysis of Controlled Trials
Authors: LIU YAOXIA , ZHANG MIN , FAN ZHEN , WANG TAO 
Published: June 2024

Objective: This systematic review aimed to assess the efficacy and safety of testosterone replacement therapy (TRT) in obese men with testosterone deficiency.
Materials and Methods: A comprehensive computer-based search was conducted in Cochrane Library, PubMed, Embase, Web of Science, Scopus, Open SIGLE database, China National Knowledge Infrastructure, Wanfang Data, VIP database, and China Biology Medicine database to identify RCTs involving obese men with testosterone deficiency treated with TRT. Methodological quality was assessed using the risk of bias assessment tool in RevMan 5.3.
Results: A total of 10 RCTs were included, involving 665 subjects at baseline. Meta-analysis demonstrated that TRT resulted in a decrease in BMI by 0.57 kg/m²(P=0.002), a reduction in waist circumference(WC) by 2.78 cm(P=0.009), an increase in lean body mass by 1.96 kg(P=0.027), a decrease in fasting blood glucose by 0.53 mmol/L(P=0.002), a decrease in HOMA-IR by 1.89 (P=0.003), a decrease in HbA1c by 0.52% (P=0.0006), and a decrease in triglycerides(TG) by 0.22 mmol/L(P=0.003). There were no statistically differences in body weight, body fat mass, non-fat body mass, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between the groups. However, TRT was associated with a statistically increase in hematocrit by 3.19% (P&lt;0.00001).
Conclusions: The study suggests that testosterone replacement therapy in obese men with testosterone deficiency can improve metabolic parameters. TRT leads to reductions in BMI, WC and TG, while increasing lean body mass and improving insulin resistance. There is a risk of increased hematocrit, and it is recommended to consider the indications for TRT and cardiovascular risks. These findings suggest a potential role for TRT in the broader management strategy for obesity-related metabolic disorders.

Disclosure
Y. Liu: None. M. Zhang: None. Z. Fan: None. T. Wang: None.
2075-LB: Identification and Characterization of Two Novel Data-Driven Subtypes of Human Obesity
Authors: FAGNOCCHI LUCA , ANDREW POSPISILIK J. 
Published: June 2024

Introduction & Objective: Obesity affects ~890 million adults and causes an estimated 5 million deaths each year. However, other than BMI and several clinical severity scales, there is no accepted framework for stratifying obesity into clinically actionable or etiologically distinct subtypes. Here, we identify and characterize two major subtypes of human obesity using a data-driven approach.
Methods: We performed multi-dimensional discordance analysis on adipose tissue gene expression profiles and morphological data from monozyogtic twins and validated the resulting two data-driven obesity subtypes against independent cohorts containing a wide range of clinical covariates.
Results: We identified two novel data-driven subtypes of human obesity, Type-A and -B, comprising ~90% of all patients with obesity. Type-A and -B are molecularly, epigenetically, morphologically, and physiologically distinct. At any given BMI, Type-B individuals exhibit relative hyperinsulinemia, relative lean mass increase, higher adipose tissue inflammation, and deregulated lipid homeostasis/adipogenesis gene expression. Mouse models and twin studies suggest that Type-B resembles a developmentally programmed obesity. These subtypes validated in the Leipzig Child Adipose Tissue cohort and in silico analysis reveal that Type-A/-B signatures can be found across the spectrum of obesity presentation. Our latest unpublished findings, integrating data available across several major obesity cohorts, indicate that Type-B obesity is reduced in insulin-responsive adipocytes (AdipoPLIN), and enriched for cardiometabolic comorbidities, irrespective of where the individuals are on the landscape of obesity.
Conclusion: Type-A and -B obesity define a major axis of human obesity heterogeneity, which might direct specific clinical intervention on patients. Type-B represents a higher risk form of obesity linked to incidence of comorbidities and suggestive of a potentially insulin-driven etiology.

Disclosure
L. Fagnocchi: None. J. Pospisilik: None.
2080-LB: Metabolite Profiles of Liver Fat and BMI in the MultiEthnic Study of Atherosclerosis (MESA) and Mediators of Atherosclerosis in South Asians Living in America (MASALA) studies
Authors: GADGIL MEGHANA D. , STROEBEL BENJAMIN M. , KANAYA ALKA M. , WOOD ALEXIS , GUO XIUQING , ROTTER JEROME I. , GREENLAND PHILIP , HERRINGTON DAVID M. 
Published: June 2024

Introduction: Hepatic steatosis occurs across the body mass index (BMI) spectrum. We aimed to identify a metabolite signature for hepatic steatosis and BMI in a diverse population.
Methods: We included participants from the MESA (n=1,226) and MASALA (N=668) cohorts with untargeted LC-MS metabolomics and abdominal computed tomography data at baseline, excluding those with cirrhosis, prevalent HIV, alcohol use &gt; 14 drinks/week or routine use of steatosis-inducing medications. There were 143 concordant metabolites between two cohorts. Log-transformed and mean-centered metabolites were used for elastic net regularized regression to select an optimal subset associated with inverse hepatic attenuation or BMI, adjusted for age, gender and BMI for hepatic steatosis analysis.
Results: There were 185 (10%) participants with hepatic steatosis, of which 48% were women, mean BMI 31 kg/m2 and 26% had prevalent diabetes. In elastic net analyses, 30 metabolites were selected for BMI, and 25 metabolites for intrahepatic fat with 6 in common. (Table)
Conclusions: Circulating triglycerides and lower lysophosphatidylcholines were predominant for hepatic steatosis while medium and long-chain acylcarnitines were related to BMI, suggesting differences in glucose and fat metabolism, respectively, between these states of excess adiposity.

Disclosure
M.D. Gadgil: Stock/Shareholder; LumosFit. B.M. Stroebel: None. A.M. Kanaya: None. A. Wood: Research Support; Beef Checkoff. Consultant; The Lundquist Institute. X. Guo: None. J.I. Rotter: None. P. Greenland: None. D.M. Herrington: None.

Funding
NIH-NIDDKK (23DK119404), NIH-NHLBI (R01HL093009), NCATS (UL1RR024131). COMBI-BIO Research supported by EU COMBI-BIO project (FP7, 305422), and NIH/NHLBI (R01HL133932). NIH-NHLBI contracts (75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169). NCATS grants (UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420).