bluuebunny/crossref_metadata_2025_split huggingface dataset:
36-OR: Modulation of Cardiorenal Benefits for GLP-1RAs Treatment by GLP1R Genetic Variants
Authors: XUE QIAOCHU , LI PIAOPIAO , PASQUEL FRANCISCO J. , PHILLIPS LAWRENCE S. , LIANG DONGHAI , VENKAT NARAYAN K M , UMPIERREZ GUILLERMO , ALI MOHAMMED K. , SHAO HUI 
Published: June 2024

Introduction: While previous research has investigated the influence of patients’ clinical characteristics on GLP-1RAs’ treatment benefits, the potential influence of genetic variants, remains insufficiently explored.
Methods: We included 3951 GLP-1 RAs new users from the All of Us program (2005-2022), and propensity-matched to a comparison group who started other second-line anti-diabetes medications. We examined 15 genetic loci significantly associated with GLP1R gene expression. Intention-to-treat analysis was performed to examine the effect of GLP-1RAs treatment with acute myocardial infarction (AMI) and acute kidney injury (AKI) using Cox proportional hazards models. Genetic variants were included as an interaction.
Results: Significant larger reductions in AMI risk were observed for eight variants (rs9296276, rs6923761, rs9296280, rs13216992, rs35887128, rs7753618, rs10305491) with GLP-1RAs treatment; and four unique variants (rs2268650, rs880347, rs5875653, rs10305439) were linked to decreased AKI risk with GLP-1RAs treatment. Polygenic scores utilizing these variants showed that higher scores were associated with higher GLP-1RA benefits in reducing AMI (high score: -59.1% vs Low: -14.4%) and AKI (high: -26.3% vs low: +36.3%) risk.
Conclusion: Our results and polygenic scores offer a pathway towards more personalization for decisions regarding GLP-1 RAs use in clinical practice.

Disclosure
Q. Xue: None. P. Li: None. F.J. Pasquel: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Ideal Medical Technologies, Novo Nordisk. Consultant; Dexcom, Inc., Medscape. L.S. Phillips: Other Relationship; Diasyst, Inc. Research Support; Kowa Pharmaceuticals America, Inc., Janssen Pharmaceuticals, Inc., AbbVie Inc., Novo Nordisk, GlaxoSmithKline plc, Abbott, Sanofi-Aventis U.S., Pfizer Inc. D. Liang: None. K. Narayan: None. G. Umpierrez: Research Support; Abbott, Bayer Inc., Dexcom, Inc., AstraZeneca. Advisory Panel; Dexcom, Inc. M.K. Ali: Advisory Panel; Eli Lilly and Company. H. Shao: Consultant; Eli Lilly and Company.
364-OR: Beta-Cell SF1 as a Thermogenic Regulator against Diet-Induced Obesity in Mice—Elucidating Its Role in Islet—Adipose Cross Talk
Authors: GUO YAN , CHENG YANGLEI , LI YANBING 
Published: June 2024

Context/Objectives: Our previous studies have established the crucial role of steroidogenic factor-1 (SF1) in beta-cell adaptation in obese mice by promoting insulin secretion. Given that deletion of SF1 in beta cells exacerbates diet-induced obesity (DIO), we aims to explore the involvement and mechanisms of SF1 in islet-adipose crosstalk and obesity related disturbance of glycometabolism.
Methods: We developed an inducible, beta-cell-specific SF1-knockout mouse model, both heterozygous and homozygous, along with control littermates of both genders. Adeno-associated virus was employed to mediate SF1 overexpression. Glucose tolerance test and insulin tolerance test were performed to evaluate glycometabolism parameters in vivo. Metabolic cages recorded food intake, physical activity and energy expenditure. Immunohistochemistry determined UCP1 and VDAC1 expression in adipocytes in brown adipose tissues (BAT), with metabonomics used to explore underlying mechanisms.
Results: The genetic deletion of SF1 in beta cells prediposed mice to obesity, glucose intolerance and insulin resistance upon high-fat diet, while ectopic SF1 expression facilitated weight loss and enhanced glucose tolerance. Notably, energy expenditure was significantly disrupted by SF1 knockout in beta cells, whereas forced expression stimulated thermogenesis. Neither food intake nor physical activity was influenced by beta-cell SF1. UCP1 and VDAC1 expression in BAT was down-regulated with beta-cell SF1 deletion but up-regulated with ectopic SF1 expression. Mechanistic investigations suggest roles for glutathione metabolism, thyroid hormone synthesis, and choline metabolism.
Conclusions: Beta-cell SF1 serves as a thermogenic enhancer in islet-adipose crosstalk thereby improving metabolic health in obese mice.

Disclosure
Y. Guo: None. Y. Cheng: None. Y. Li: Consultant; Sanofi, Novo Nordisk, AstraZeneca.

Funding
National Natural Science Foundation of China (82200876)
368-P: Identifying Causes and Improving Hypoglycemia in Hospitalized Patients—An Update
Authors: ZONFA IAN C. , LEWIS CLAUDIA , GALLOWAY NICHOLAS R. , HATIPOGLU BETUL , TSUSHIMA YUMIKO 
Published: June 2024

Introduction & Objective: Hypoglycemia is known to increase morbidity, mortality, and lengthen hospital stay leading to increased health care costs. The purpose of our study is to investigate the prevalence and identify causes and risk factors contributing to inpatient hypoglycemia. We report findings from two of our largest community hospitals in combination with our previously reported data from a tertiary referral center to better represent the general population.
Methods: We performed a retrospective cross sectional analysis of adult patients 18 years and older who were admitted to two of our community hospitals and had a hypoglycemic event, defined as glucose ≤55 mg/dL. A chart review, during a six month period in 2022 and 2023, was conducted to identify causes and associated comorbidities. We incorporated data from our previously reported tertiary care center findings.
Results: We evaluated 1,928 episodes of hypoglycemia occurring in 1,044 adult patients hospitalized across 3 hospitals. 57% of the patients had diabetes mellitus. Hypoglycemia occurred most frequently due to decreased caloric intake related to critical illness (53%) followed by insulin-induced hypoglycemia (39%). In patients without diabetes, 75% of hypoglycemic events were due to decreased caloric intake and critical illness. Kidney failure (32%), coronary artery disease (20%) and malignancy (15%) were the comorbidities most frequently associated with hypoglycemia.
Conclusion: Hypoglycemic events were most frequently caused by decreased caloric intake and insulin administration. Within the 40% of patients who did not have diabetes, 75% had hypoglycemia due to decreased caloric intake. This sheds light onto a population which has traditionally not been associated with hypoglycemia. Identifying patients at risk for hypoglycemia, improving nutritional status in critically ill patients and optimizing glycemic monitoring/insulin management are areas where intervention can improve inpatient hypoglycemia rates.

Disclosure
I.C. Zonfa: None. C. Lewis: None. N.R. Galloway: Consultant; Tidepool. Board Member; Association Diabetes Care and Education Specialists. B. Hatipoglu: Research Support; Tandem Diabetes Care, Inc. Y. Tsushima: None.
369-P: How Common Is Fear of Hypoglycemia in Type 1 Diabetes Mellitus and Type 2 Diabetes Mellitus? (iNPHORM, USA)
Authors: RATZKI-LEEWING ALEXANDRIA , BLACK JASON E. , ZOU GUANGYONG , RYAN BRIDGET L. , HARRIS STEWART B. 
Published: June 2024

Introduction & Objective: Fear of hypoglycemia (FoH) is linked to diminished diabetes clinical and psychosocial outcomes; yet its real-world burden in the United States remains poorly quantified. We analyzed iNPHORM data to address this gap.
Methods: Adults (≥18 years old) with T1DM or T2DM on insulin and/or secretagogues were recruited from a US-wide, probability-based internet panel. Online screening, baseline, and 12-month follow-up questionnaires (FQ) captured data prospectively. We measured FoH at FQ Month 6 using the Hypoglycemia Fear Survey II, which comprises Worry and Behaviour subscales. Per assessment guidelines, we calculated absolute total and subscale-specific FoH scores, and prevalences of elevated versus non-elevated scores, overall and by diabetes type. Wilcoxon rank-sum tests and Z-tests assessed differences in T1DM and T2DM responses (α=0.05).
Results: N=781 were analyzed (T1DM: 18.4%; age: 51.2 [SD: 14.6] years; male: 50.7%; retention rate: 64.8%). All T1DM respondents used insulin; among those with T2DM, 40.2% used insulin without secretagogues, 36.7% used secretagogues without insulin, and 23.1% used both. Median absolute FoH Worry and Behaviour subscale scores were 30 [IQR: 21] and 29 [IQR: 18], respectively. For both subscales, absolute scores were higher in T1DM than T2DM (Worry subscale: 35 [T1DM] vs. 29 [T2DM], p=0.003; Behaviour subscale: 32.5 [T1DM] vs. 28 [T2DM], p&lt;0.001). The overall prevalence of elevated FoH was 16.3% (T1DM: 19.4%; T2DM: 15.5%, p-value=0.25). For Worry and Behaviour subscales, 15.0% (T1DM: 14.6%; T2DM: 15.1, p-value=0.88) and 16.3% (T1DM: 17.4%; T2DM: 16.0%, p-value=0.69) reported elevated scores, respectively.
Conclusion: Despite greater absolute FoH scores in T1DM, we observed no significant differences in elevated FoH prevalences by diabetes type. Our results underscore the high and ubiquitous burden of FoH in diabetes. Clinical interventions should target not only people with T1DM but also T2DM, including those on secretagogues without insulin.

Disclosure
A. Ratzki-Leewing: Research Support; Sanofi. Advisory Panel; Dexcom, Inc. Consultant; Abbott. Advisory Panel; Sanofi-Aventis U.S. Other Relationship; American Diabetes Association. Consultant; Novo Nordisk, Eli Lilly and Company. J.E. Black: None. G. Zou: None. B.L. Ryan: None. S.B. Harris: Consultant; Abbott. Research Support; Boehringer-Ingelheim. Consultant; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company, Novo Nordisk, Sanofi. Research Support; Novartis AG. Consultant; Bayer Inc.

Funding
The iNPHORM study was funded through an investigator-initiated grant from Sanofi Global.
373-P: Gastric Pouch Emptying Rate in Post-bariatric Hypoglycemia
Authors: TURK NICOLE , MORADI FARSHAD , AYHAN EKREM M. , MCLAUGHLIN TRACEY 
Published: June 2024

Roux-en-Y gastric bypass surgery (RYGB) promotes long term remission of T2D in up to 90% of patients. Approximately 38%, however, develop post bariatric hypoglycemia (PBH), with 11.8%. Why some and not others develop this complication is unknown. We have previously shown that altered nutrient transit, with overstimulation of hind gut causes postprandial hypoglycemia via hypersecretion of GLP1 and insulin, which is reversible by restoring normal route of nutrient transit or by blocking GLP1. We hypothesized that following surgery, individuals with faster pouch emptying would comprise a group at higher risk for developing PBH. We tested this hypothesis by quantifying pouch emptying rates in post-RYGB patients with and without PBH.15 RYGB patients with PBH, 10 postsurgical controls (without PBH), and 12 nonsurgical BMI-matched controls underwent a solid meal scintigraphy with dynamic imaging for 60 minutes followed by additional imaging at 2, 3, and 4 hours to quantify pouch emptying rate. Both PBH and postsurgical controls had markedly accelerated pouch emptying as compared to nonsurgical controls (p=9.8E-7, and 0.0059, respectively). The PBH group had significantly faster emptying at 1-hour in comparison to the post-surgical controls (5.9% vs 17.8% residual, respectively; p=0.024).
Conclusion: PBH individuals have more rapid pouch emptying versus post-surgical controls, pointing to a potential route for treatment or prevention of PBH.

Disclosure
N. Turk: None. F. Moradi: Research Support; GE health care, Ashvattha Therapeutics. E.M. Ayhan: None. T. McLaughlin: Stock/Shareholder; Eiger BioPharmaceuticals. Board Member; January, Inc. Research Support; Eli Lilly and Company, Weight Watchers International, Merck & Co., Inc., Vogenyx.

Funding
American Diabetes Association (1-19-ICTS-073)
38-OR: Implementation of an EHR-Integrated Hospital-Wide CGM Protocol for Insulin Dosing
Authors: SEAV SUSAN M. , YEH LEE MING , ONGWELA LOICE , AUBYRN RACHEL , CAO FANG , LEE JULIE J.H. , KALINSKY ANNA F. , APARICIO RAMOS OLIVIA M. , GU YUNZI M. , IVANOVIC MAJA M. , BUCKINGHAM BRUCE A. , DESAI DIMPI , LAL RAYHAN , TAN MARILYN , BASINA MARINA , HUGHES MICHAEL S. 
Published: June 2024

Objective: The study aimed to develop and assess a standardized electronic health record (EHR)-integrated hospital-wide protocol for personal continuous glucose monitor (CGM) use and CGM-based insulin dosing. The focus was on feasibility and acceptability from nurses and patients.
Methods: At Stanford Health Care, a hospital-wide protocol was implemented to support inpatient use of home CGM devices in lieu of frequent fingerstick blood glucose (FSBG) monitoring for insulin dosing. It includes requirements specific to each CGM device and protocols for ongoing accuracy monitoring through intermittent CGM-to-FSBG comparisons (“validations”) integrated directly into the EHR. User experience surveys were conducted among a subset of patients and nurses who used the protocol.
Results: From Nov 2022-Aug 2023, 135 patients used a personal CGM under the protocol in 185 inpatient encounters. This included 26% non-English speakers and 27% with type 1 diabetes. Most used CGMs were Dexcom G6 (44%), Libre 2 (42%), and Libre 3 (5%). Automated insulin delivery was used in 23% of encounters. Of 1506 CGM validations, 87.7% met the requisite accuracy criteria (“%20/20”) for CGM-based insulin dosing, and 99.3% fell within Clarke zones A or B. Surveys were completed by 27 nurses and 46 patients. A majority of nurses found glucose management under the protocol effective (74%), easy to use (67%), and efficient (63%); 80% of nurses preferred inpatient CGM to FSBG. A majority of patients liked glucose management under the CGM protocol (63%), reported positive interaction with nursing staff about CGM use (63%), and felt the number of interruptions related to diabetes management was reasonable (63%).
Conclusion: The inpatient CGM protocol, fully EHR-integrated and with real-time device accuracy monitoring, allowed for insulin dosing based on personal CGM data. It received favorable feedback from both nurses and patients, and is the first to offer guidance for multiple CGM types, tailored individually according to CGM type.

Disclosure
S.M. Seav: None. M. Lee: None. L. Ongwela: None. R. Aubyrn: None. F. Cao: None. J.J.H. Lee: None. A.F. Kalinsky: None. O.M. Aparicio Ramos: None. Y.M. Gu: None. M.M. Ivanovic: None. B.A. Buckingham: Advisory Panel; Medtronic. Research Support; Medtronic. Advisory Panel; Arecor. D. Desai: None. R. Lal: Consultant; Abbott, Adaptyx Biosciences, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Tidepool. Advisory Panel; Lilly Diabetes. M. Tan: None. M. Basina: None. M.S. Hughes: Consultant; Dexcom, Inc.

Funding
National Institutes of Health (5K12DK122550, 1K23DK122017, T32DK007217, P30DK116074)
381-P: Hypoglycemia and Hyperglycemia among Elderly Patients in Long-Term Care Facilities
Authors: SCHMIDT VANESSA , LANE KYRSTIN , LEE ROGER M. , FREEBY MATTHEW 
Published: June 2024

Background: Hypoglycemia and hyperglycemia episodes are common in older adults living in long-term care (LTC) facilities, but often go undetected due to clinical complications and comorbidities in the elderly. There is limited data evaluating the frequency of hypoglycemia and hyperglycemia in the elderly who live in LTC facilities. We aimed to investigate and define hypoglycemia frequency (blood glucose &lt;70 mg/dL) and hyperglycemia frequency (blood glucose &gt;250 mg/dL) in the elderly at LTC facilities.
Methods: Patients with diabetes at the LTC facility were included if they were ≥65 years and their diabetes regimen included insulin or sulfonylurea therapy. Frequency of hypoglycemia and hyperglycemia was evaluated through the use of Freestyle Libre Pro CGM and events detected were compared to available finger-stick measurements over a 10-14 day period.
Results: Seventy-one percent of patients had at least one episode of hypoglycemia. 100 percent (106/106) of hypoglycemic episodes were captured by CGM but unrecognized by fingerstick. Forty-eight percent of patients had at least one episode of hyperglycemia.
Conclusion: There is high frequency of hypoglycemic and hyperglycemic episodes in older adults. Our study shows that the use of professional CGM in elders in LTC facilities can provide an in-depth assessment of hypoglycemia events and hyperglycemia events when combined with finger-stick glucose monitoring.

Disclosure
V. Schmidt: Research Support; Abbott. K. Lane: None. R.M. Lee: None. M. Freeby: Research Support; Abbott, Fractyl Health, Inc., Novo Nordisk.

Funding
Abbott Diabetes Care Inc (ADC-SRR-IIS-18-22)
390-P: Construction of a PANoptosis-Related Gene Signature for Diabetic Nephropathy
Authors: CHEN YAN 
Published: June 2024

Background: In this study, we aimed to develop a diagnostic model for DN based on PANoptosis-related genes.
Methods: DEGs associated with DN were identified in the GSE96804 and GSE142025 datasets. Functional analyses included GO and KEGG. PANoptosis-related DEGs were also identified by intersecting PANoptosis-related genes with DEGs. Pairwise correlations among these genes were assessed via Pearson correlation analysis. Immune cell abundance in DN patients versus controls was compared in GSE96804. Feature genes for DN prediction were selected with machine learning, and a diagnostic model was constructed using LASSO regression. High-risk and low-risk groups were established based on risk scores, with GSEA used to explore enriched biological processes and pathways. The association between risk scores and immune cell infiltration was examined using CIBERSORT. Potential therapeutic drugs were investigated via the DGIdb database.
Results: We identified 573 DEGs_com in DN. Six PANoptosis-related DEGs were found, showing co-regulation and potential functional interactions. NMF classified patients into two clusters. Immune cell analysis revealed significant differences in abundance between DN patients and controls, with variations in dendritic cells, macrophages, mast cells, and neutrophils. Three feature genes (PDK4, YWHAH, PRKX) were selected for a diagnostic model, yielding high diagnostic accuracy for DN across multiple datasets (AUC = 0.8-1.0) and a reliable nomogram for DN prediction. Stratification based on the risk score revealed significant associations between risk levels and immune cell infiltration patterns. PPI network and correlation analyses indicated potential therapeutic targets (PRKX, PDK4) and drugs were identified.
Conclusions: The integration of PANoptosis-related genes PDK4, YWHAH, and PRKX offers a promising diagnostic model for DN, providing a novel diagnostic tool and potential targeted therapeutic strategies for DN management.

Disclosure
Y. Chen: None.

Funding
Youth of National Natural Science Foundation of China ( 82001480)
399-P: Association of Social Determinants of Health with Initiation of Novel Glucose-Lowering Drugs in Patients with Diabetes—A Post Hoc Analysis of the Kidney-CHAMP Trial
Authors: MOSSLEMI MITRA , WELTMAN MELANIE , LAVENBURG LINDA-MARIE U. , ALGHWIRI ALAA , YABES JONATHAN , HAN ZHUOHENG , COSTACOU TINA , JHAMB MANISHA 
Published: June 2024

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are recommended but underutilized in patients with diabetic kidney disease, with different patterns of disparities reported. How social determinants of health (SDOH) shape disparities in SGLT-2i/GLP-1 RA initiation remains to be elucidated. We investigated the SDOH factors associated with SGLT-2i/GLP-1 RA initiation vs. nonuse, among participants with type 2 diabetes and chronic kidney disease enrolled in the Kidney Coordinated HeAlth Management Partnership (Kidney-CHAMP) trial (2019-2022). In the Kidney-CHAMP subpopulation of 890 participants with type 2 diabetes who were not using SGLT-2i/GLP-1 RA at baseline (age: 18-85 yrs., eGFR: 15-30 mL/min/1.73m2), 32% initiated SGLT-2i/GLP-1 RA during the 3-year follow-up period. In multivariable mixed model analysis, age, primary insurance category, and distance to nearest health clinic were the SDOH factors that remained significantly associated with SGLT-2i/GLP-1 RA initiation (Table 1). Our results suggest that access-to-care factors may play a pivotal role in the inadequate adoption of SGLT-2i/GLP-1 RA, emphasizing the need for further research into the mechanisms underlying the impact of SDOH factors on SGLT-2i/GLP-1 RA uptake.

Disclosure
M. Mosslemi: None. M. Weltman: None. L.U. Lavenburg: None. A. Alghwiri: None. J. Yabes: Other Relationship; Bayer Inc. Z. Han: None. T. Costacou: None. M. Jhamb: Research Support; Bayer Inc., Pfizer Inc. Advisory Panel; Eli Lilly and Company, Boehringer-Ingelheim, Xcenda LLC, CKD Networks of Excellence.
40-OR: The Association of Continuous Glucose Monitoring Metrics with Hospital-Related Clinical Outcomes
Authors: FLINT KRISTEN L. , O'CONNOR MOLLIE , SABEAN AMY , ASHLEY ANNABELLE , ZHENG HUI , YAN JOYCE , STEINER BARBARA , ANANDAKUGAN NILLANI , CALVERLEY MELISSA M. , BARTHOLOMEW RACHEL , GREAUX EVELYN , CASTELLANOS LUZ E. , LARKIN MARY E. , RUSSELL STEVEN J. , PUTMAN MELISSA S. 
Published: June 2024

Introduction: Few studies have examined the association between continuous glucose monitoring (CGM) metrics and hospital-related clinical outcomes in the inpatient setting.
Methods: In this prospective observational study, patients admitted on non-intensive care floors receiving fingerstick glucose monitoring wore blinded Dexcom G6 Pro CGM during their hospital stay. Clinical data were extracted from the medical record including a composite of infection, DKA/HHS, renal replacement therapy, or thrombosis. Readmissions and emergency department (ED) visits within 30 days of discharge were identified through record review and participant phone interview. The associations between CGM metrics and clinical outcomes were assessed with multivariable logistic regression.
Results: In this cohort of 326 adults (78% type 2 diabetes, 12% type 1 diabetes, 10% other), median % time in range 70-180 mg/dL was 44.5% (17.1, 70.2%), % time &gt;180 mg/dL (TAR) was 54.8% (28.8, 82.3%), and % time &lt;70 mg/dL (TBR) was 0% (0, 0.2%). Multivariable regression analyses demonstrated a significant association of 30-day ED visits with increased %TAR (p = 0.01) and borderline association of 30-day readmissions and %TBR (p = 0.06) (Table 1).
Conclusion: Hyperglycemia identified by CGM was associated with 30-day ED visits, suggesting CGM could help identify patients that may benefit from increased support after hospital discharge.

Disclosure
K.L. Flint: None. M. O'Connor: None. A. Sabean: None. A. Ashley: None. H. Zheng: None. J. Yan: None. B. Steiner: None. N. Anandakugan: None. M.M. Calverley: None. R. Bartholomew: None. E. Greaux: None. L.E. Castellanos: None. M.E. Larkin: None. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. Other Relationship; Beta Bionics, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk. M.S. Putman: Research Support; Dexcom, Inc. Other Relationship; Vertex Pharmaceuticals Incorporated. Research Support; Vertex Pharmaceuticals Incorporated. Advisory Panel; Anagram Therapeutics.

Funding
National Institutes of Health (R01 DK119699-02S1); National Institutes of Health (T32DK007028); Dexcom Investigator Initiated Study Grant