bluuebunny/crossref_metadata_2025_split huggingface dataset:
291-OR: A Noninvasive Index for Significant Liver Fibrosis and Stratifying Risk of Cirrhosis in Patients with Type 2 Diabetes Mellitus in Primary Care
Authors: QI XIAOLONG , YOU DONGFANG , SHEN JIE , LIU CHUAN , CHEN YUPING , ZHENG MING-HUA , ZHOU XIQIAO , HUANG MINGXING , LIANG XUAN , DENG TIANXURUN , SUN CHAO , LIANG XIAO , WAN HENG , WANG YAN , ZHU YONGFEN , LV FANGFANG , ZHOU TAOLONG T. , LIU SHANGHAO , WANG XIAOMEI , LIU XING , HE RUILING , LI JIE , ZHAO YANG , WONG VINCENT W. 
Published: June 2024

Introduction & Objective: To propose a non-invasive index for detecting patients with T2DM at risk of significant liver fibrosis and cirrhosis in primary care.
Methods: Five cohorts consist of 38,160 adults with T2DM were enrolled to develop and validate a non-invasive index for evaluating significant liver fibrosis and cirrhosis (Figure A).
Results: Risk factors including Aspartate transaminase and boDy mass inDex were fitted to develop a test, termed the ADD index (available at: https://chess.nuist.edu.cn/consult/gzconsult/add_index). Using transient elastography (TE) as the reference, the ADD index performed better than FIB-4 and NFS for significant fibrosis (Figure B). A cutoff of 0 of the ADD index was selected to stratify patients into low- and high-risk group that should receive TE. AUC of the ADD index followed by TE was significantly higher than that of FIB-4 and NFS followed by TE (Figure B). Notably, using the ADD index combined with TE resulted in 11% cost savings compared to use TE alone. Compared with patients in low-risk group, those in high-risk group had a 2.90-fold (95% CI:1.44-5.82, P &lt; 0.01) risk for cirrhosis (Figure C).
Conclusions: The non-invasive ADD index can be applied to screen significant fibrosis and cirrhosis in patients with T2DM in primary care, and promoting those in high-risk group to further consult a hepatologist in secondary care.

Disclosure
X. Qi: None. D. You: None. J. Shen: None. C. Liu: None. Y. Chen: None. M. Zheng: None. X. Zhou: None. M. Huang: None. X. Liang: None. T. Deng: None. C. Sun: None. X. Liang: None. H. Wan: None. Y. Wang: None. Y. Zhu: None. F. Lv: None. T.T. Zhou: None. S. Liu: None. X. Wang: None. X. Liu: None. R. He: None. J. Li: None. Y. Zhao: None. V.W. Wong: Consultant; AbbVie Inc., Boehringer-Ingelheim, Echosens, Gilead Sciences, Inc. Research Support; Gilead Sciences, Inc. Consultant; Intercept Pharmaceuticals, Inc., Inventiva Pharma, Novo Nordisk, Pfizer Inc., Sagimet Biosciences.
292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets
Authors: SAKUMA IKKI , GASPAR RAFAEL C. , NASIRI ALI , KAHN MARIO , GUERRA MATEUS , YIMLAMAI DEAN , MURRAY SUE , PERELIS MARK , BARNES WILLIAM , VATNER DANIEL F. , PETERSEN KITT , SAMUEL VARMAN , SHULMAN GERALD I. 
Published: June 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is highly prevalent among patients with type 2 diabetes. Cholesterol is one of several candidates causing hepatic inflammation and fibrosis. We hypothesized that by interrupting the synthesis of cholesterol, we could prevent a choline-deficient L-amino acid-defined high-fat diet (CDAHFD) C57BL/6J MASH mouse model. We found that cholesterol in liver lipid droplets accumulated on day 1, MASH-associated macrophage markers (Gpnmb and Trem2) mRNA expression and plasma ALT increased on day 2, macrophage crown-like-structures emerged on day 3, and fibrosis markers (Col1a1, αSMA) mRNA expression increased on day 7 in the CDAHFD-treated mice. Filipin staining demonstrated free cholesterol accumulation in liver lipid droplets. We next examined whether a N-acetylgalactosamine-modified antisense oligonucleotide (ASO) against coenzyme A synthase (Coasy), which catalyzes a rate controlling step in hepatic cholesterol synthesis, would reduce cholesterol in liver lipid droplets and inflammation/fibrosis in this model. Coasy ASO treatment prevented accumulation of cholesterol in liver lipid droplets (Control=1.02 ± 0.04 mg/g tissue; Coasy=0.68 ± 0.08, P&lt;0.001) and decreased plasma ALT and liver inflammation/fibrosis markers expression. To examine whether these effects of the Coasy ASO were mediated by reductions in liver lipid droplet cholesterol we examined whether adding 2% cholesterol to the diet would prevent the Coasy ASO protective effect. Cholesterol treatment induced accumulation of cholesterol in liver lipid droplets (Coasy=0.68 ± 0.08 mg/g tissue; Coasy with cholesterol =1.40 ± 0.11, P&lt;0.001) and abrogated the protective effects of the Coasy ASO on liver inflammation and fibrosis.
Conclusions: These data demonstrate that cholesterol in liver lipid droplets is a key mediator of MASH and hepatic Coasy knockdown is a potential therapeutic approach.

Disclosure
I. Sakuma: None. R.C. Gaspar: None. A. Nasiri: None. M. Kahn: None. M. Guerra: None. D. Yimlamai: None. S. Murray: Employee; Ionis Pharmaceuticals. M. Perelis: Employee; Ionis Pharmaceuticals. W. Barnes: Employee; Ionis Pharmaceuticals. D.F. Vatner: None. K. Petersen: None. V. Samuel: None. G.I. Shulman: None.
299-OR: Discovery of Long-Acting Unimolecular Peptide Tetra-agonists Targeting GLP-1, GIP, Amylin, and Calcitonin Receptors for Enhanced Metabolic Benefits in Animal Models of Obesity
Authors: GHOSH SOUMITRA , VALDECANTOS PILAR , RADA PATRICIA , VALVERDE ANGELA M. , RONDINONE CRISTINA M. 
Published: June 2024

Objective: The burgeoning prevalence of obesity and associated co-morbidities necessitates innovative approaches for safe and efficacious therapies. We describe the characterization of PTT-A, a novel long-acting peptide agonist for GLP-1, GIP, Amylin and Calcitonin Receptors, in rodent models and assessed its efficacy against the dual GIPR/GLP-1R agonist Tirzepatide.
Methods: In vitro assays used recombinant cell lines expressing individual receptors to assess GLP-1, GIP, Amylin and Calcitonin receptor agonism. Multiple metabolic endpoints were examined in rodents, including acute food intake and calcium regulation effects of PTT-A in lean rats, acute glucose-lowering effects in lean mice, and its chronic effects in diet-induced obesity (DIO) rats compared to Tirzepatide.
Results: PTT-A exhibited potent GIP, GIP, Amylin, and Calcitonin receptor agonism in cAMP assays, and induced decreases in blood glucose and calcium levels in acute studies in lean rodents. In lean rats, PTT-A dose-dependently reduced cumulative food intake. Chronic studies in DIO rats revealed significant reduction in cumulative food intake and body weight, driven by decreases in fat mass without loss of muscle mass, unlike that seen with Tirzepatide. PTT-A demonstrated robust efficacy for glucose and plasma lipid lowering, insulin sensitization and liver benefits, as indicated by lowered plasma insulin, alanine aminotransferase and liver triglycerides, while outperforming Tirzepatide at equivalent doses.
Conclusion: PTT-A is a novel tetra-receptor agonist, offering superior outcomes for weight loss, glycemic control, insulin sensitization, and liver health compared to Tirzepatide. These findings underscore the promise of such poly-pharmacological agents to tackle the complex challenges associated with obesity-related metabolic disorders.

Disclosure
S. Ghosh: Consultant; Abvance Therapeutics, Akero Therapeutics, Inc., Fractyl Health, Inc., Takeda Pharmaceutical Company Limited. P. Valdecantos: Research Support; Pep2Tango Therapeutics INC. P. Rada: Research Support; Pep2Tango Therapeutics INC. A.M. Valverde: Research Support; Pep2Tango Therapeutics INC. C.M. Rondinone: Board Member; Pep2tango Therapeutics Inc. Stock/Shareholder; Pep2tango Therapeutics Inc.
30-OR: Diabetes Rescue, Engagement, and Management (D-REM)—Results of a Pragmatic Clinical Trial of a Community Paramedicine Program to Improve Diabetes Care
Authors: DUCHARME-SMITH ALLISON , MCCOY ROZALINA G. , MEILANDER ANGELA K. , FISCHER KAREN , LIEDL CHAD , QUILLEN JAXON , JUNTUNEN MICHAEL B. 
Published: June 2024

Introduction & Objective: People living with diabetes face multiple barriers to care and health, including gaps in access to medical care and diabetes self-management education/support (DSMES) and high costs of care. These challenges are particularly great for those living in rural areas. Community paramedics (CPs) are well positioned to deliver DSMES to patients with clinical and psychosocial complexities as part of an interdisciplinary clinical team. CPs are experienced paramedics with advanced training in the management of low acuity and chronic conditions who practice under the supervision of a physical medical director to provide a wide range of services tailored to each patient’s needs. While CP models have emerged across the U.S. and world to support transitional care, CPs have not been leveraged specifically for DSMES.
Methods: D-REM was a pilot pragmatic single-arm prospective trial of a community paramedic (CP) DSMES program that enrolled 70 adults with diabetes, hemoglobin A1c (HbA1c) ≥9%, and recent emergency department or hospital care for any cause. Participants received at-home CP care for approximately one month. Outcomes were ascertained from electronic health record review and postal surveys at 1- and 4-months.
Results: Enrolled participants were 61 (52.3-67.2) years old, 52.9% were men, and 50% lived in rural areas. D-REM resulted in 1.6% improvement in HbA1c, from 9.8% (8.9-10.6) at enrollment to 8.2% (7.1-9.3) at 4 months (p=0/02). It also improved engagement with primary care, endocrinology, and in-clinic DSMES. Participants were highly satisfied with their care.
Conclusion: CP is an emerging and scalable model of care delivery that can support diabetes management for patients experiencing clinical and structural barriers to care. Further research is needed to examine the effectiveness and implementation of CP programs in different settings and populations.

Disclosure
A. Ducharme-Smith: None. R.G. McCoy: Research Support; American Diabetes Association. Other Relationship; American Diabetes Association. Consultant; Wolters Kluwer Health. Research Support; National Institutes of Health, Patient-Centered Outcomes Research Institute. Consultant; Yale New Haven Health System. A.K. Meilander: None. K. Fischer: None. C. Liedl: None. J. Quillen: None. M.B. Juntunen: None.
31-OR: ROCKET Type 1 Diabetes—Launching Diabetes Self-Management Habits in Youth with New-Onset Type 1 Diabetes
Authors: ALARCON GUIDO , SONABEND RONA Y. , SCHWARTZ DAVID D. , LYONS SARAH , DESALVO DANIEL 
Published: June 2024

Introduction: Performing the 6 T1D self-management habits (SMH) (Figure 1) has been associated with lower A1c and increased time in range (TIR) (Lee et al., JAMA Netw Open, 2021). We developed a remote patient monitoring program (RPM), called ROCKET T1D (Remote Outreach & Care for Kids’ Empowerment and Technology use in T1D), to optimize diabetes management in new onset T1D. We aimed to increase use of the 6 SMH by ≥ 2 habits from baseline in &gt;80% of youth with newly diagnosed T1D.
Methods: At program launch, all youth with new onset T1D entered the ROCKET T1D RPM program within 2 weeks of diagnosis. After baseline assessment of the SMH, a CDCES conducted weekly virtual visits focused on each of the habits. After 3-month program completion, CDCES reassessed the SMH. CGM metrics were obtained in the first 2 weeks and again at program completion.
Results: Among 71 patients who completed the program, the mean cumulative habit score increased from 3.1 to 5.2, and 81% increased ≥ 2 habits from baseline. Mean TIR increased (56% to 64%, p=0.02) and mean GMI decreased (7.6% to 7.3%, p=0.07).
Conclusion: Remote support with tailored education following T1D diagnosis resulted in improved T1D management habits. CGM metrics were promising, but this could be due to other factors such as partial remission. Future work should evaluate whether early intensive education and technology initiation provides longterm glycemic benefit.

Disclosure
G. Alarcon: None. R.Y. Sonabend: None. D.D. Schwartz: None. S. Lyons: None. D. DeSalvo: Advisory Panel; Insulet Corporation. Consultant; Dexcom, Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (2206-05307)
312-OR: OPAT Is Protective of Major Amputation following Hospitalization for Diabetic Foot Infection
Authors: TARRICONE ARTHUR , GEE ALLEN , REYES MARIO C. , LAVERY LAWRENCE A. , ROGERS LEE C. 
Published: June 2024

Introduction & Objectives: Diabetic foot ulcers are a common complication of diabetes associated with high morbidity and mortality. It is estimated that the United States spends up to $13 billion USD each year on DFUs, with individual costs rising to $15,000 per year. Much of this expenditure has been attributed to lengthy hospital stays and inpatient care, with the need of prolonged antibiotic therapy. Outpatient antibiotic therapy (OPAT) is a service that provides intravenous antimicrobial medication in the outpatient setting and has been shown to reduce hospital stay and overall medical costs. This study aims to determine the benefit of OPAT therapy in a cohort with soft tissue and bone foot infections.
Methods: Prospective cohort study of patients hospitalized for diabetic foot infection. Patients were grouped by discharge status : OPAT program or standard of care. All patients were followed for a minimum of one year. Statistics were performed using Stata Be7. Continuous variables were reported as mean ± standard deviation and categorical variables were reported as their n(%). Odds ratios were written as O.R, followed by their associated confidence interval [CI]. Significance was determined as p≤0.05.
Results: A total of 246 patients were hospitalized with lower extremity infections in this cohort. OPAT was used in 93(38%) patients and 152(62%) with standard of care. The outcomes examined in this study included reinfection, binary wound healing, amputations, and major amputations. OPAT was found to be protective for major amputations ( OR= .21, 0.05-0.98, p=0.046). No difference was seen between reinfection ( OR=0.55, 0.28-1.09, p=0.085 ), binary wound healing ( OR=0.85, 0.50-1.45, p=0.54 or minor amputations ( OR=0.67, 0.22-1.95, p=0.45).
Conclusion: OPAT is protective against major amputation however does not reduce reinfection, improve binary wound healing, or reduce minor amputations.

Disclosure
A. Tarricone: None. A. Gee: None. M.C. Reyes: None. L.A. Lavery: None. L.C. Rogers: None.
32-OR: First Impact on A1C of Medically Underserved Patients with Type 2 Diabetes Using a Hybrid Chronic Care Model
Authors: LEE JOYCE Y. , SEO MINJONG , NGUYEN JENNY T. , RODRIGUEZ ALLEN , RODRIGUEZ VANESSA , CHAN ALEXANDRE , MAYORGA JOSE 
Published: June 2024

Timely access to care is crucial for effective diabetes management, but social determinants of health often present significant obstacles. A hybrid chronic care model (h-CCM), which combines pharmacist-conducted telemedicine visits with in-person provider visits, was established to minimize health disparities through enhanced options for healthcare delivery. This study was designed to compare the first A1C changes among medically underserved patients with T2D who received diabetes care from h-CCM versus usual care. This was a prospective intervention study conducted at a FQHC located in Southern California between Oct 2021 and Dec 2022. Patients ≥ 40 years with T2D who received h-CCM (intervention) were compared to the control or usual care which included in-person provider visits only. The control data were generated from UCI Data Warehouse (UCI IRB#2636), matched 1:1 by age, gender, ethnicity, and baseline A1C of the intervention arm during the same time period. Descriptive statistics and Student’s t-test were utilized to compare the demographics and clinical characteristics between the two arms. A total of 208 patients (I: 104, C: 104) were included in the analysis. The average age for both arms was 61.0 SD ±10.5 years with majority being female (57.7%) and Latinx (70%), and a mean A1C of 9.4 ±1.5%. The mean baseline 10-year ASCVD score (%) was comparable (I:19.6 ±16.6 vs. C:22.6 ±17.2; p=0.202). At 3 months, the A1C for the intervention and control arms were 8.74 ±1.89% and 9.41 ±0.12%, respectively, with an average A1C reduction of 0.7% (95% CI: 0.3-1.0, p &lt;0.001%) observed in the intervention arm and no change in the control. A minimal mean (±SD) % reduction for the ASCVD score was observed in the intervention arm (-0.6 ±5.5) with worsening trend observed in the control (0.2 ±1.9).
In conclusion, h-CCM appeared to effect a quicker improvement in A1c during the first three months of care implementation when compared to usual care in medically underserved patients.

Disclosure
J.Y. Lee: None. M. Seo: None. J.T. Nguyen: None. A. Rodriguez: None. V. Rodriguez: None. A. Chan: None. J. Mayorga: None.
354-OR: The Role of Clic-Like Chloride Channel 1 in the Pancreatic Beta Cell
Authors: ZHANG YAOHUAN , YIV NICHOLAS , SHARIATI KAAVIAN , SANFILIPPO ANDREW , KU GREGORY M. 
Published: June 2024

Chloride is one of the most abundant electrolytes and has many important physiological functions. Though it is known that chloride plays a role in beta cell physiology and insulin secretion, intracellular chloride fluxes and how they affect beta cell development and function are relatively poorly understood. Clic-like chloride channel 1 (Clcc1) is an endoplasmic reticulum (ER) localized chloride channel whose loss causes ER stress and cell death in neurons and retinal cells. We found that Clcc1 beta cell specific knockout (Clcc1 beta-KO) mice were glucose intolerant with lower plasma insulin and pancreatic insulin content at 10 weeks of age. We found that fewer Clcc1 beta-KO mouse beta cells were dividing at 21 days of age, suggesting reduced neonatal beta cell expansion. Beta cell area was reduced by 50% at 10 weeks of age, but surprisingly, we found a 95% reduction in islets that could be isolated by traditional collagenase digestion of the pancreas, suggesting that adult Clcc1 beta-KO mouse islets were structurally altered. This islet fragility was age dependent; normal numbers of islets could be isolated from Clcc1 beta-KO mice up to 14 days of life. These islets had normal glucose stimulated insulin secretion but had 50% less insulin content compared. Single cell RNA-sequencing showed fewer proliferating beta cells but no obvious unfolded protein response. Our data shows that Clcc1 has a surprising role in islet structure, insulin production and beta cell growth. Our research is currently focused on understanding the effect of loss of Clcc1 on ER chloride flux and the mechanism of how that might affect islet structure, beta cell function, and growth.

Disclosure
Y. Zhang: None. N. Yiv: None. K. Shariati: None. A. Sanfilippo: None. G.M. Ku: None.

Funding
National Institutes of Health (TR004204); National Institutes of Health (DK1249040; Sandler Program for Breakthrough Biomedical Research UCSF
360-OR: Defining New Targets for Interventions to Increase Continuous Glucose Monitoring (CGM) Use in Primary Care
Authors: MILOSAVLJEVIC JOVAN , MATHIAS PRIYANKA M. , SCHECHTER CLYDE , AGARWAL SHIVANI 
Published: June 2024

Background: CGM is a standard of care for diabetes management, yet its adoption in primary care remains limited where the majority of people with diabetes are served. Examining contributors to CGM prescriptions in primary care may identify new targets for intervention that could improve diabetes population health.
Methods: We examined CGM prescription behaviors of primary care providers within a large safety net hospital in the Bronx, NY. We extracted data from the electronic health record on all adults ≥18 years with type 2 diabetes and at least one primary care visit from July 31, 2020, to July 31, 2023. We used competing risk regression to model factors associated with CGM prescription.
Results: Out of 40,791 people with type 2 diabetes (mean age 62 years, 60% female, 39% Hispanic, 39% Non-Hispanic Black, 77% English-speaking, 47% publicly insured, 27% seen by trainee physicians), 4,129 (10.1%) were prescribed CGM. CGM was 40% less likely to be prescribed for Spanish vs. English-speaking (SHR 0.60 [0.54-0.68]), 15% less likely with public insurance (SHR 0.85 [0.79-0.91]), and 25% less likely with diabetes complications (microvascular SHR 0.73 [0.67-0.79], macrovascular SHR 0.77, [0.69-0.86]). Conversely, CGM was 30% more likely to be prescribed with each additional HbA1c percentage point (SHR 1.31 [1.30-1.34]) and 6% more likely with each additional prescriber year of experience (SHR 1.06, [1.05-1.07]). CGM prescriptions increased in a dose-response manner with treatment intensification (non-insulin SHR 2.08 [1.76, 2.46]; basal insulin SHR 3.94 [3.27-4.75]; multiple daily insulin SHR 5.03 [4.17-6.07]).
Conclusion: Our analysis of a large primary care network of people with diabetes can inform strategies to support more widespread CGM use in primary care. New targets could include Spanish language support services; aid for better prior authorization procedures for public insurance; and increased education of CGM benefits for providers with less years of experience.

Disclosure
J. Milosavljevic: None. P.M. Mathias: None. C. Schechter: None. S. Agarwal: Research Support; Dexcom, Inc. Advisory Panel; Medtronic. Consultant; Beta Bionics, Inc.
365-OR: Maladaptive Sensory Plasticity via α2δ1-subunit Promotes Adipose Tissue Lipolysis after Spinal Cord Injury
Authors: ROY DEBASISH , DION ELLIOT G. , SEPEDA JESSE A. , PENG JUAN , TOWNSEND KRISTY L. , SAS ANDREW , SUN WENJING , TEDESCHI ANDREA 
Published: June 2024

Spinal cord injury (SCI) leads to a progressive decline in metabolic homeostasis. Thus far, it is unclear whether the underlying cause of metabolic complications after SCI may be linked to the dysregulation of adipose tissue. The sympathetic nervous system and sensory neurons with cell bodies located in the dorsal root ganglia (DRG) innervate white adipose tissue (WAT). However, the extent to which sensory innervation drives WAT function under normal and pathophysiological conditions has remained elusive. To investigate structural changes in WAT, we subjected adult mice to a thoracic (T)12 SCI that completely transected sensory axons without impacting sympathetic nerve activity. Whereas no changes were observed in iWAT, we found an increase in the percentage of small-size adipocytes in eWAT, a phenotype associated with rapid lipid partitioning. Our biochemical and molecular analysis confirmed that SCI exacerbates lipolysis in eWAT but not in iWAT. After injury, maladaptive reorganization of neuronal circuits can cause aberrant neuron firing that eventually culminates in the onset of post-traumatic disorders. We and others have demonstrated a strong convergence between the rearrangement of neuronal circuits and the expression of α2δ subunits of VGCC. α2δ subunits positively regulate neurotransmitter release by increasing plasma membrane expression of VGCC. We discovered that α2δ1 expression increases in CGRP+ DRG neurons that project to eWAT 7 days after SCI. Conditional deletion of the gene encoding α2δ1 in these neurons normalizes eWAT lipolysis after SCI. Using a clinically relevant strategy, we demonstrated that α2δ1 pharmacological blockade also normalizes eWAT lipolysis after SCI, thereby preventing ectopic lipid accumulation in the liver. Thus, our study provides novel insight into the molecular basis of maladaptive sensory processing in eWAT, facilitating the development of strategies to promote metabolic health after SCI.

Disclosure
D. Roy: None. E.G. Dion: None. J.A. Sepeda: None. J. Peng: None. K.L. Townsend: None. A. Sas: None. W. Sun: None. A. Tedeschi: None.

Funding
National Institute of Neurological Disorders and Stroke (R01NS110681), National Institute of Health (P30CA016058)