bluuebunny/crossref_metadata_2025_split huggingface dataset:
805-P: Double-Blind Crossover Study of Ultra-Rapid AT247 Compared with NovoLog and Fiasp during Continuous Subcutaneous Infusion (CSII) Assessed by a Hyperinsulinemic Euglycemic Clamp
Authors: HOMPESCH MARCUS , LAWRENCE FIONA J. , JEZEK JAN , GERRING DAVID J. , PIEBER THOMAS 
Published: June 2023

Background: AT247 is a novel insulin aspart formulation designed for ultra rapid absorption following subcutaneous injection to achieve optimal postprandial glycemic control.
Method: Adults (29) with T1DM were randomized to 6 treatment sequences of AT247, Novolog (N), and Fiasp (F). Bolus (0.15 U/kg) and basal (0.02 U/kg/h) doses of insulin were administered via CSII for 3 days. PK and PD were assessed using euglycemic clamps on days (D) 1 and 3.
Results: A higher early insulin exposure (AUCIns 0-30min mU/L/h) was observed for AT247 (16.7) vs N (6.3*) or F (13.0**) on D1, Fig 1A. The difference for AT247 was maintained on D3 (20.8) vs N (10.5*) but not vs F (19.2). A higher early glucose lowering effect (AUCGIR 0-60 mins mg/kg) was observed for AT247 (144.4) vs N (70.4*) but not vs F (145.8) on D1 only, Fig 1B. Time to early 50% Cmax insulin (h) occurred earlier for AT247 (0.18) compared to N (0.43*) and F (0.28**) on D1 and D3 (AT247 0.17; N 0.33**; F 0.22**). Statistical significance was p&lt;0.05* or p&lt;0.01**. AT247 was well tolerated with no significant adverse effects.
Conclusions: The faster absorption of AT247 resulted in higher early insulin exposure than for F or N following bolus dose delivery during CSII. The demonstrated PK profile of AT247 supports further investigation into its potential to further improve automated insulin delivery.

Disclosure
M.Hompesch: Board Member; ProSciento, Consultant; Wiley-Blackwell, Employee; ProSciento, Stock/Shareholder; ProSciento. F.J.Lawrence: None. J.Jezek: None. D.J.Gerring: Employee; Arecor. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics.
806-P: Once Weekly (QW) Basal Insulin Fc (BIF) and Daily Degludec (DEG) Achieve Comparable Glycemic Control in Three Patient Populations Studied during Phase 2—Clinical Insights from CGM Assessments
Authors: KAZDA CHRISTOF M. , BUE-VALLESKEY JULIANA M. , ZHANG QIANYI , HAUPT AXEL , FRIAS JUAN P. , DAHL DOMINIK 
Published: June 2023

BIF is a fusion protein combining a novel single chain insulin variant with a human IgG Fc domain.
Three randomized, open-label, treat-to-target phase 2 studies of 26 or 32 week duration assessed 912 people with T2D previously treated with basal insulin (T2D-Switch) or new to insulin therapy (T2D-Naïve), or T1D on multiple daily injections (T1D). Studies assessed QW BIF vs once daily DEG. Key results were previously disclosed and met the primary endpoint of non-inferiority in HbA1c change from baseline (non-inferiority margin=0.4%). Two studies had CGM during entire study and T2D-Naïve had blinded, intermittent CGM using 14-day sessions.
Patients had baseline HbA1c of 8.1, 8.0, and 7.5% for T2D-Switch, T2D-Naïve, and T1D respectively. Figure shows average hourly mean glucose at endpoint and time in range (inset). Glucose profiles appeared comparable between treatments with 24-hour average glucose for BIF vs DEG in T2D-Naïve: 137 vs 127 mg/dL p=.042 and T1D: 175 vs 169 p=.075 (T2D-Switch not available). Average duration of hypoglycemia, &lt;70mg/dL (min) per patient for BIF vs DEG: T2D-Switch 31 vs 35 p=NS, T2D-Naïve 51 vs 91 p&lt;.001, and T1D 35 vs 35 p=NS.
QW BIF achieved similar glycemic control vs DEG as seen in several CGM derived measures providing useful and reassuring insights into the use of QW BIF in these patient populations.

Disclosure
C.M.Kazda: Employee; Eli Lilly and Company. J.M.Bue-valleskey: Employee; Eli Lilly and Company. Q.Zhang: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. D.Dahl: Research Support; Lilly, Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim Inc., Amgen Inc.

Funding
Eli Lilly and Company
807-P: Patient and Health Care Provider Experiences of Suboptimal Insulin Dosing in the United States
Authors: DAVIDSON MICHAEL B. , GELSEY FELICIA , BOWER JULIE , ARTIME ESTHER , SPAEPEN ERIK , NEWSON RACHEL 
Published: June 2023

Objectives: This study described the frequency of suboptimal insulin dosing (missed and mistimed doses) and the factors underlying this behavior from the perspective of people with diabetes (PwD) and healthcare professionals (HCPs.)
Methods: For this cross-sectional, multinational non-interventional study, 640 HCPs and 1150 PwD (300 with type 1 diabetes, 850 with type 2 diabetes) completed an online survey. A research vendor recruited adult PwD currently using a non-connected insulin pen (400 from US) and eligible HCPs (160 from US) via validated panels, referrals, list acquisition, and custom methods. Results are presented for US data.
Results: Overall, 42% and 61% of PwD reported missing basal and bolus insulin doses in the past 30 days. The average number of missed basal and bolus doses were 3.1 (SD=3.81) and 5.0 (SD=10.30), respectively. PwD reported forgetting, being too busy/distracted, and out of my normal routine as key reasons for missed doses. Overall, 37% and 49% of PwD reported mistiming basal and bolus doses, respectively, in the past 30 days. This corresponded to an average of 3.1 (SD=3.29) mistimed basal and 4.9 (SD=6.28) mistimed bolus doses. Key reasons PwD reported for mistimed doses included being too busy/distracted, forgot or having an unexpected or earlier/later-than-expected meal. Conversely, the majority of HCPs reported ≤20% of their PwD missed/skipped a dose in the past 30 days. HCPs reported dosing reminders (90%), automatically recorded insulin doses and timing (92%) and having insulin and glucose data in one place (94%) as identified solutions.
Conclusions: PwD are missing, skipping, or delaying their insulin doses, largely for preventable reasons. HCPs perceive PwD dosing adherence greater than PwD self-reported behaviors. Digital health solutions, such as connected insulin pens, may help PwD reduce missed and mistimed doses as well as help close the perception gap to further optimize insulin management.

Disclosure
M.B.Davidson: Employee; Eli Lilly and Company. F.Gelsey: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Bower: None. E.Artime: None. E.Spaepen: Consultant; Eli Lilly and Company. R.Newson: Employee; Eli Lilly and Company.

Funding
Eli Lilly and Company
81-OR: The Rnf20 Ubiquitin Ligase Is Required for Beta-Cell Identity and Function
Authors: PIERRE TANYA , LIU YANPING , HUNTER CHAD S. 
Published: June 2023

Type 1 and Type 2 Diabetes are characterized by a loss of functional β-cell mass. With the incidence of diabetes rising globally, a better understanding of the gene regulatory mechanisms maintaining β-cell functional identity is imperative to improve diabetes therapies. Islet 1 (Isl1) is a LIM-homeodomain class transcription factor that is essential for β-cell maturation and function. Our previous Isl1 studies revealed that it interacts with the histone ubiquitin ligases Ring Finger 20 (Rnf20) and Rnf40 in mouse β-cells, mouse islets, and human islets. Rnf20 and Rnf40 act as homo- or heterodimeric complexes wherein they monoubiquitinate histone 2B to regulate transcription. In mouse β-cell lines, we demonstrated that Rnf20 and Rnf40 are important for β-cell gene expression and insulin secretion, perhaps mediated by their occupancy of Slc2a2 and MafA. Additionally, using proximity ligation assay we showed a robust increase in Isl1 and Rnf20 interactions under high glucose conditions. Based on these findings, we hypothesized that at least Rnf20 is required for β-cell function in adult islets. To evaluate the contribution of Rnf complexes to β-cell maintenance, we developed an adult-inducible Rnf20 β-cell-specific knockout mouse model, termed Rnf20Δβ-cell. By 8 weeks of age (2 weeks after tamoxifen induction) male and female Rnf20Δβ-cell mice became hyperglycemic, severely glucose intolerant, and had reduced plasma insulin levels following a glucose challenge. Additionally, Rnf20Δβ-cell mice had reduced β-cell mass, in parallel with dysregulated expression of glucose-stimulated insulin secretion and β-cell identity mRNAs including Ins I, Slc2a2, Ucn3, Ngn3, and Aldh1a3. Our in vivo findings resemble those observed in adult Isl1 knockout mice. Paired with similar changes in gene expression in the Rnf20 and Isl1 models, and the glucose-responsive interaction between Isl1 and Rnf20 in vitro, our data support the hypothesis that Isl1-Rnf complexes are critical regulators of β-cell function.

Disclosure
T.Pierre: None. Y.Liu: None. C.S.Hunter: None.

Funding
National Institutes of Health (DK111483, DK128132)
812-P: Tight vs. Standard Inpatient Glycemic Targets in Non–Critical Care Settings—A Propensity Scored–Matched Analysis of Insulin-Treated Patients with Type 2 Diabetes
Authors: SALING JARROD , MIGDAL ALEXANDRA L. , URRUTIA MARIA A. , ZABALA ZOHYRA , MOAZZAMI BOBAK , GALINDO RODOLFO J. , FAYFMAN MAYA , RASHIED AMMAR A. , UMPIERREZ GUILLERMO 
Published: June 2023

Differing blood glucose (BG) targets are recommended by professional organizations in noncritical care settings. Previous Endocrine Society and ADA guidelines recommended a target BG of 70-140 and 140-180 mg/dl; however, the 2023 ADA Standards of Care recommends a target of 100-180 mg/dl. The lack of consensus is due to the lack of randomized clinical trials (RTC) to support a tight vs relaxed BG target. We performed a post-hoc analysis on 9 RCTs to assess hospital outcomes in non-critically ill insulin-treated subjects with T2D targeting BG 70-140 mg/dL vs. 140-180 mg/dL. Among 1446 patients, 640 were treated to a target of 70-140 mg/dl and 806 to a target of 140-180 mg/dL. Propensity score matching was used to reduce the bias including sex, HbA1c, and home insulin use, for a final count of 1,146 patients (573 subjects in each target group). Patients in the tight BG target group had lower mean BG (163.73±39.79 vs 170.15±39.94 mg/dL, p=0.004), less hyperglycemia (BG &gt;180: 86% vs 92%, p=0.003; BG &gt;240: 51% vs 62%, p&lt;.001), similar rates of hypoglycemia (BG &lt;70: 12% vs 15%, p=0.11; BG &lt;54: 2.5% vs 4.0%, p=0.14). The intensive target resulted in a shorter length of stay (4.0 vs 6.0 days, p&lt;.001) and lower composite of complication rate (acute kidney injury, infection, myocardial infarction, respiratory failure and stroke) (3.7% vs 6.8%, p=0.02) than the relaxed BG target, with similar mortality rates (0.9% vs 0.3%, p=0.36). There were no differences in glycemic variability (GV) between groups with greater GV in those experiencing hypoglycemia &lt;70 mg/dL or hyperglycemia &gt;200 mg/dL. Our results indicate that lower BG target of 70-140 mg/dl leads to lower mean daily BG, less severe hyperglycemia events, similar rates of hypoglycemia and glycemic variability, and lower length of stay and complication rates compared to a higher target of 140-180 mg/dl. RCTs are indicated to elucidate optimal glycemic targets in hospitalized patients with T2D.

Disclosure
J.Saling: None. A.L.Migdal: None. M.A.Urrutia: None. Z.Zabala: None. B.Moazzami: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. M.Fayfman: None. A.A.Rashied: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Funding
Jacob Family Funds
813-P: Bridging Dose of U-100 Glargine with First Dose of Insulin Degludec Improves Glycemia in the 48 Hours after Transition In Twice-Daily Glargine Users
Authors: THIRUMALAI ARTHI , CHAO JING H. , KALERU THANMAI , DONG XIAOFU , MANDAVA PATALI , KHAKPOUR DORI , HIRSCH IRL B. 
Published: June 2023

Background: Degludec (D), a once-daily basal insulin, takes 2-3 days to achieve steady state. When transitioning from insulin glargine (G) to D, 1:1 conversion is recommended. We studied the off-label effects of a bridging dose of G with the first dose of D in type 1 diabetes (T1D) patients using a continuous glucose monitor (CGM) 48 hours before and after the transition.
Methods: Patients with T1D on a stable G regimen and A1C &lt;9% were randomized (double-blind) to a dose of placebo or G with first dose of D. Patients transitioned to D at 80% of total baseline G dose, based on result of SWITCH 1 clinical trial of transition to D. Bridging dose of G was 50% of total daily G dose for patients on once daily (QD) regimen at baseline and 50% of evening G dose in those on twice daily (BID) G and was taken with only the first dose of D. All participants wore a study CGM (Dexcom G6) and were instructed to manage their diabetes as usual except for not administering correctional doses of insulin unless glucose was greater than 250 mg/dL in the 48 hours before and after first dose of D.
Results: Forty participants were randomized and 37 completed the study. The study population was 65% male with mean age of 47 years, 22 years duration of T1D, BMI 26 kg/m2, A1C of 6.8% and total daily insulin dose of 0.7 units/kg body weight. Nineteen patients (12 QD, 7 BID) received a bridging dose of G with their first dose of D; 18 patients (12 QD, 6 BID) received placebo. Among the BID users, patients bridged with G had a mean 9% increase in time in range (70-180 mg/dL) on CGM, while placebo patients had a mean 12% decrease (p=0.003). Time above range (180-250 mg/dL) also showed a mean 11.4% decrease in the BID users bridged with G, contrasted with an 11.5% increase in BID users on placebo (p=0.002). There were no significant differences in time below ranges (&lt;70 mg/dL, &lt;54 mg/dL).
Conclusions: Well-controlled twice-daily G users transitioning to D may benefit from a 50% bridging dose of evening G with first dose of D.

Disclosure
A.Thirumalai: Research Support; Novo Nordisk, Fractyl Health, Inc. J.H.Chao: None. T.Kaleru: None. X.Dong: None. P.Mandava: None. D.Khakpour: None. I.B.Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc.

Funding
Novo Nordisk (ISS001250)
818-P: Glycemic Control in Naïve Users of Second-Generation Basal Insulins with T2D and CKD—A Nationwide Register-Based Cohort Study
Authors: KOSJERINA VANJA , CARSTENSEN BENDIX , AMADID HANAN , VISTISEN DORTE 
Published: June 2023

Objective: We aimed to compare the effectiveness and safety of second-generation basal insulins, insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (Deg-100), in terms of change in HbA1c, hospitalization for hypoglycemia and all-cause mortality.
Methods: In this register-based cohort study, using real-word data on the entire Danish diabetes population in the period 2013-2020, we included 6519 naïve users of Gla-300 or Deg-100 with T2D and chronic kidney disease (CKD). Change in HbA1c, from initiation of either study drugs to end of follow-up, was modeled with mixed-effect models while rates of hospitalization for hypoglycemia and all-cause mortality were modeled in separate Poisson models.
Results: Mean HbA1c levels were reduced by 13-14 mmol/mol over a four-year period in both groups with no significant difference (Figure). The rate of hospitalization for hypoglycemia was slightly but not significantly higher in the Deg-100 group (rate-ratio 1.03 (CI 95%: 0.71, 1.49) while the all-cause mortality rate was slightly but not significantly lower in the Deg-100 group (0.97 (0.83, 1.14)).
Conclusion: We found no difference in HbA1c reduction, hospitalization for hypoglycemia or all-cause mortality between Gla-300 and Deg-100, in a real-world population of naïve users with T2D and CKD.

Disclosure
V.Kosjerina: Research Support; Sanofi-Aventis Deutschland GmbH. B.Carstensen: Stock/Shareholder; Novo Nordisk. H.Amadid: Employee; Novo Nordisk A/S. D.Vistisen: Research Support; Bayer Inc., Sanofi, Boehringer-Ingelheim, Stock/Shareholder; Novo Nordisk A/S.

Funding
Sanofi-Aventis Deutschland GmbH
821-P: Treatment and Outcomes of Nonemergent Hyperglycemia in the Emergency Department
Authors: MURPHY KRISTA , LACY MARY E. , HEIER KORY , CLAAS STEVEN A. , KECK JAMES 
Published: June 2023

Background: Patients with hyperglycemia often seek care in the emergency department (ED). Hyperglycemia is associated with longer hospital stays and increased risk of mortality.
Methods: Using electronic health record data from patients ≥18 seen at an academic medical center ED (11/1/2015-12/31/2020), we described presentation of non-emergent hyperglycemia (blood glucose (BG) 180-600mg/dL) and examined associations between insulin receipt in ED and in-hospital mortality and hospitalization. We excluded patients with initial BG &gt;600mg/dl, decompensated diabetes, stroke, myocardial infarction, pregnancy, or sepsis, and calculated National Early Warning Score to control for illness severity. We examined associations between insulin receipt and hospitalization and mortality in patients with BG 180-600mg/dL using logistic regression, and stratified analyses by diabetes diagnosis and BG value to assess for effect modification.
Results: Of 177,176 eligible patients, 10.9% (19,378) had BG 180-600mg/dL (mean (SD) age=54.6 (15); 52.5% male). Of these patients, 6.8% (1,312) received insulin, 41.8% (8,097) were hospitalized, and 0.3% (278) died. Regression results appear in Figure 1.
Conclusions: Hyperglycemia in the ED was common. Treatment with insulin, though uncommon, yielded lower odds of mortality but not hospitalization. Diabetes diagnosis and severity of hyperglycemia modified this association.

Disclosure
K.Murphy: None. M.E.Lacy: None. K.Heier: None. S.A.Claas: None. J.Keck: None.

Funding
National Institutes of Health (UL1TR001998)
822-P: Machine Learning Guided Interpretation of Point-of-Care Ultrasound to Diagnose Lipohypertrophy
Authors: MADDEN KENNETH M. , BANDARI ELA , HABASHY LARA , RAZA JAVAIRIA , KAPELUTO JORDANNA E. , MENEILLY GRAYDON S. 
Published: June 2023

Objective: Using a supervised machine learning convolutional neural network (CNN) we developed a model to detect lipohypertrophy (LH) using point-of-care ultrasound (PoCUS) images.
Research Designs and Methods: Using a PoCUS ultrasound machine (GE LOGIQe, 5-18 MHz probe), images were obtained by a single, blinded technician. We then split the data set into training (70%), validation (15%) and testing (15%) splits. To improve the generalizability of the model, we used image augmentation techniques (randomly changing contrast, brightness, etc). We considered recall and accuracy of our models when testing the various architectures on our testing dataset. An YOLOv5m object detection model was used to place bounding boxes around LH lesions.
Results: The learning architectures investigated were VGG16, ResNet50, DenseNet169, and InceptionV3. The highest recall (76%) and accuracy (76%) was found using the DenseNet CNN architecture. As shown in the figure, YOLOv5m was able to identify LH locations with a F1 score of 0.78 and a confidence value of 0.41.
Conclusions: We were able to use a DenseNet CNN architecture to automatically detect the presence of LH lesions on PoCUS images obtained at the bedside.

Disclosure
K.M.Madden: None. E.Bandari: None. L.Habashy: None. J.Raza: None. J.E.Kapeluto: None. G.S.Meneilly: None.

Funding
Allan M. McGavin Foundation
823-P: GLY-200, a Pharmacologic Duodenal Exclusion Therapy, Improved Metabolic Parameters in the DIO Rat
Authors: NIMGAONKAR ASHISH , BRYANT CHRISTINE , HABEGGER KIRK M. , COLBERT KEVIN , CARLSON TAYLOR , POLOMOSCANIK STEVEN , PETERSEN JOHN S. , JOZEFIAK THOMAS H. , FINEMAN MARK 
Published: June 2023

Non-invasive alternatives to metabolic surgery or duodenal exclusion devices for type 2 diabetes (T2D) and obesity are lacking. We developed an orally administered therapeutic polymer, GLY-200, designed to create a barrier in duodenum by complexing with mucin. In healthy subjects, 5 days treatment resulted in significant reductions in postprandial glucose and insulin and increases in bile acids and gut hormones. To evaluate the chronic effects of GLY-200, we conducted an 8-week study in the diet-induced obesity (DIO) rat model.
Methods: DIO rats (60% kcal fat diet) were gavaged once daily following a 3-hour fast with GLY-200 (120 mg/rat) or saline (n=12/group). Metabolic assessments included body weight, mesenteric fat mass, skeletal muscle mass (gastrocnemius), glycemic responses to an oral glucose tolerance test (oGTT), and gut hormones from fasted samples at study termination.
Results: At 8 weeks, GLY-200 treated rats had a significant reduction in % body weight gain (5%, p &lt; 0.05), lower mesenteric fat mass (p &lt; 0.01), and a significant reduction in incremental glucose AUC0-120 min following the oGTT on Day 51 (p &lt; 0.05) compared to control. These metabolic benefits were associated with a significantly higher fasting active GLP-1 level compared to control (p &lt; 0.01). Trends for increased PYY were also observed as compared to control. There was no difference in skeletal muscle mass.
Conclusions: In the DIO rat, chronic (8-weeks) once-daily treatment with GLY-200 resulted in significant improvements in metabolic parameters compared to saline control consistent with a duodenal exclusion MOA. These results support further development of GLY-200 for the treatment of T2D and obesity.

Disclosure
A.Nimgaonkar: Employee; Glyscend Inc. C.Bryant: Employee; Glyscend Inc. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Glyscend Inc., Stock/Shareholder; Glyscend Inc. K.Colbert: Consultant; LifeSprout, Employee; Glyscend Inc. T.Carlson: Employee; Glyscend Inc. S.Polomoscanik: None. J.S.Petersen: None. T.H.Jozefiak: Employee; Glyscend Inc., Stock/Shareholder; Glycologix, LLC. M.Fineman: Employee; Glyscend Inc., Stock/Shareholder; Glyscend Inc.