bluuebunny/crossref_metadata_2025_split huggingface dataset:
820-P: The Proposed Insulin Lispro Biosimilar GN1101DP Shows Pharmacokinetic (PK) and Pharmacodynamic (PD) Bioequivalence to Humalog in Caucasian and Chinese Healthy Subjects
Authors: HEISE TIM , ZIJLSTRA ERIC , ANDERSEN GRIT , SELKER STEFFEN B. , SHEN CHUN , WANG YUN 
Published: June 2023

This randomized, double-blind, cross-over study compared PK/PD-properties of Humalog and GN1101DP, a proposed insulin lispro (INS) biosimilar with an identical primary structure and high physicochemical and bio-functional similarity to Humalog. Thirty-five Caucasian and 13 Chinese healthy subjects completed the study and received a single dose of 0.3 U/kg of GN1101DP and Humalog under euglycemic automated glucose clamp conditions (ClampArt®, plasma glucose (PG) target 81 mg/dL, clamp duration 12 hours post-dose, wash-out period 2-14 days between the two dosings). Plasma INS concentrations were determined by tandem ultra performance liquid chromatography-mass spectrometry. GN1101DP demonstrated both PK- and PD-bioequivalence to Humalog with superimposable INS concentration and glucose infusion rate (GIR) profiles, point estimates close to 100%, and 90% confidence intervals were within the pre-defined similarity range of 80-125%. Bioequivalence was observed in all and also separately in Caucasian and Chinese subjects (Figure). Clamp quality was high (mean PG-variations of ~5% and deviations from target &lt;0.6 mg/dL). Both lispro formulations were well tolerated. No injection site reactions occurred. In conclusion, GN1101DP demonstrated PK- and PD-bioequivalence to Humalog in Caucasian and Chinese subjects.

Disclosure
T.Heise: Advisory Panel; Novo Nordisk, Consultant; Gan & Lee Pharmaceuticals, Research Support; Adocia, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. E.Zijlstra: Other Relationship; Eli Lilly and Company, Speaker's Bureau; Gan & Lee Pharmaceuticals, Novo Nordisk A/S. G.Andersen: None. S.B.Selker: None. C.Shen: None. Y.Wang: None.

Funding
Genova Biotech Pvt. Ltd.
888-P: Urinary Albumin Levels Prior to SGLT2 Inhibitors Initiation Predict Increased TIR after 12 Months in Patients with Type 1 Diabetes on Sensor-Augmented Pump Therapy
Authors: SUGANUMA YUKA , TAKAHASHI HIROSHI , OHNO TAKAYUKI , NISHIMURA RIMEI 
Published: June 2023

Purpose: SGLT2 inhibitors (SGLT2i) have been shown to improve glycemic control in patients with type 1 diabetes (T1D). Predictors of SGLT2i efficacy in patients with T1D on sensor-augmented pump (SAP) therapy were investigated.
Methods: Patients with T1D on SAP therapy attending our hospital who were newly initiated on SGLT2i between 2019-2020 and followed for at least one year, were included in the study. Data on BMI, blood tests, and continuous glucose monitors were compared before and 12 months after SGLT2i initiation. The predictors of time in range (TIR) change (ΔTIR) were determined by multiple regression analysis. The cutoff values for predictors of ΔTIR above the median at the end of the study were determined using ROC curve analysis.
Results: 17 patients (70.6% females, median age 44.0 years) were included in the analysis, except for three patients who discontinued SGLT2i due to side effects. Median BMI and eGFR decreased significantly from 25.3 kg/m2, and 79.0 ml/min/1.73m2 at baseline to 23.9 kg/m2, and 73.0 ml/min/1.73m2 (p = 0.013, p = 0.002, respectively), while total daily dose of insulin, basal-to-total insulin ratio, and urinary albumin-to-creatinine ratio (UACR) showed no significant change (40.1 vs 41.0 units [p = 0.084], 40.1 vs 38.5% [p = 0.266], 7.0 vs 2.0 mg/g [p = 0.285], respectively). HbA1c, TIR, and TAR improved significantly (8.2 vs 7.8% [p = 0.004], 53.0 vs 61.0% [p = 0.003], and 47.0 vs 36.0% [p = 0.003], respectively), while TBR showed no significant change (0.4 vs 0.8% [p = 0.309]). Predictors of increased ΔTIR were overweight and high UACR at baseline (p = 0.026) and the cutoff value for UACR that predicted ΔTIR above the median was 28.0 mg/g (AUC = 0.82 [95%CI, 0.61-1.03]; p = 0.003).
Conclusion: SGLT2i improved glycemic control of patients with T1D on SAP therapy without increasing TBR. It was also suggested that patients with UACR above 28.0 mg/g could have greater impact on TIR improvement after 12 months.

Disclosure
Y.Suganuma: None. H.Takahashi: Speaker's Bureau; Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Medtronic, Novo Nordisk. T.Ohno: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca.
89-LB: Oral Delivery of a GLP-1 Agonist with High Bioavailability in Dogs and Humans
Authors: VO APRIL T. , YAMAGUCHI ALYSON , DHALLA ARVINDER , HORLEN KYLE , FUNG LEONARD , SYED BABER , IMRAN MIR , HASHIM MIR 
Published: June 2023

GLP-1 mimetics, which are highly efficacious as antidiabetic agents, are also proving to be effective for weight loss, albeit at higher doses. While most require injections due to poor oral bioavailability, Rybelsus® (semaglutide) is orally effective for glycemic control, however, its 1% bioavailability and high dose requirement limits its viability as an effective oral weight-loss medication. Here, we demonstrate high oral bioavailability of the GLP-1 agonist, exenatide, A) in canines using an orally ingestible robotic pill (RP) which painlessly injects drug transenterically in the proximal small bowel and B) in humans using an endoscopically guided transenteric injection which mimics RP delivery. Awake dogs received 10 µg of exenatide orally via RP (RT-104, N=4) or SC injection (Byetta®, N=5), while 5 healthy human volunteers received 10 µg of Byetta® via an endoscopic, transenteric injection and, after a 3-day washout, via a SC injection. Exenatide concentrations, determined via ELISA in serially collected plasma samples, yielded similar PK curves in both species (Figure) with oral bioavailability via RP or endoscopic injection calculated to be 79% in dogs and 81% in humans, respectively, compared to SC injections. These data provide the basis for further development of an orally ingestible GLP-1 mimetic (RT-104) which would provide the higher, efficacious exposures needed for both weight loss and glycemic control.

Disclosure
A. T. Vo: None. A. Yamaguchi: None. A. Dhalla: Employee; Rani Therapeutics. K. Horlen: Employee; Rani Therapeutics. L. Fung: None. B. Syed: None. M. Imran: Board Member; Neptune Medical, Other Relationship; InCube Ventures, Modulus, Inc. M. Hashim: None.
92-OR: The Survival and Function of Whole or Dissociated Islet Transplants Are Improved by Immunomodulatory Microporous Annealed Particle (MAP) Gel
Authors: MA MINGYANG , ROOSA COLLEEN A. , GRIFFIN DONALD R. , BRAYMAN KENNETH L. , CHHABRA PREETI 
Published: June 2023

The aim was to investigate if MAP gel can support the function of whole islets or dissociated islet cells, and improve transplantation under kidney capsule or within the epididymal fat pad. A) Whole or dissociated BL/6 islets were transplanted into syngeneic diabetic recipients in the presence or absence of MAP gel. 100 islets were transplanted under the kidney capsule (n=6/group). Mice receiving transplant within the fat pad were divided into 6 groups (n=2/group): 300 whole islets; 400 dissociated islets; MAP gel alone; and 200, 300 or 400 dissociated islets with MAP gel. Blood glucose (BG) was measured daily. B) MAP gel or NP gel was transplanted within the fat pad of NOD mice (n=4/group) to analyze the immune response. Graft-containing fat pad was excised 6 weeks post-transplantation and analyzed for cytokines by flow cytometry. Our results indicated that transplantation of dissociated islets and MAP gel under the kidney capsule permanently restored normoglycemia within 18 days. In contrast, uncoated dissociated islet cells failed to reverse diabetes. Treatment efficacy continued 40 days post-transplantation, the entire period of observation. At Day 30, average BG was 163±38mg/dL. Diabetic mice transplanted with dissociated islet cells without MAP gel remained hyperglycemic. Transplantation of 400 dissociated islet cells with MAP gel within the fat pad also achieved normal BG levels that continued 44 days post-transplantation, the period of observation. In contrast, transplantation of MAP gel, or 300 whole islets, or dissociated islets alone into the fat pad, failed to reverse diabetes. An upregulation of IL-10 and downregulation of IL-6 was observed only in the graft microenvironment of the MAP gel group, validating the immunomodulating capacity of MAP gel. To conclude, MAP gel can promote transplantation outcomes under the kidney capsule or within the fat pad by improving the survival and function of both, whole and dissociated islets.

Disclosure
M.Ma: None. C.A.Roosa: None. D.R.Griffin: Board Member; Tempo Therapeutics. K.L.Brayman: None. P.Chhabra: None.

Funding
LaunchPad for Diabetes Innovation Fund (GF004946); LaunchPad for Diabetes Ignite Program (169098)
920-P: Effects of Hybrid Closed-Loop System on Glycemic Control and Psychological Aspects in Persons with Type 1 Diabetes Treated with Sensor-Augmented Pump—A Prospective Single-Center Observational Study
Authors: AKIYAMA TOMOAKI , ORIME KAZUKI , YAMAKAWA TADASHI 
Published: June 2023

Introduction Since the Medtronic 770G hybrid closed-loop (HCL) system was approved in Japan in 2022, we evaluated the effects of the HCL system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus (T1DM) treated with the Medtronic 640G predictive low glucose suspend (PLGS) system. Materials and Methods In a 3-month prospective observational study, 21 people with T1DM (mean age: 48.7 years; male: 5 people) treated with PLGS system were enrolled. The participants switched to the 770G system, where the algorithm maintains glucose levels at 120 mg/dl, and in 3 months the percentage of time in blood glucose range (TIR) 70-180 mg/dl and glycated hemoglobin level (HbA1c) were evaluated. Self-reported questionnaires were administered at baseline and in 3 months to assess their satisfaction, emotional distress, and quality of life (QoL), using Diabetes treatment satisfaction questionnaire status (DTSQs), Problem area in diabetes scale (PAID), and Diabetes therapy-related QoL (DTR-QoL), respectively. Results In 3 months, TIR increased from 63.2 ± 13.7% to 72.7 ± 11.1% (mean ± standard deviation) (P &lt; 0.0005), whereas time above blood glucose range (TAR) 181-250 mg/dl decreased from 26.9 ± 9.1% to 19.7 ± 7.2 % (P &lt; 0.0005). TAR &gt; 250 mg/dl, time below blood glucose range (TBR) 54-69 mg/dl and TBR &lt; 54 mg/dl did not differ significantly. HbA1c decreased from 7.7 ± 1.0% to 7.2 ± 0.8% (P = 0.0013). There were no significant changes in DTSQs, PAID, and DTR-QOL in 3 months (DTSQs 26.7 ± 6.0 compared with baseline 26.9 ± 4.0, P = 0.87, PAID 52.3 ± 17.9 compared with baseline 54.0 ± 16.3, P = 0.48, DTR-QoL 50.1 ± 19.0 compared with baseline 47.0 ± 16.9, P = 0.38). Conclusion HCL system could increase TIR, compared with PLGS system, without worsening treatment satisfaction, emotional distress, and QoL. This study suggested HCL system is useful for Japanese people with T1DM.

Disclosure
T. Akiyama: None. K. Orime: None. T. Yamakawa: None.
923-P: CamAPS FX Hybrid Closed-Loop with Ultra-Rapid Insulin Lispro Increases Time in Range Compared with Standard Insulin Lispro in Adults with Type 1 Diabetes—A Double-Blind, Randomized, Crossover Study
Authors: NWOKOLO MUNACHISO , LAKSHMAN RAMA , BOUGHTON CHARLOTTE K. , WARE JULIA , ALLEN JANET M. , WILINSKA MALGORZATA E. , ALWAN HEBA , EVANS MARK , HOVORKA ROMAN 
Published: June 2023

Aim: To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) in adults with type 1 diabetes (T1D).
Methods: In a double-blind, randomized, crossover study, 28 adults with T1D (mean±SD; age 44.5±10.7 years, HbA1c 7.1±0.9% [54±10mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with Lyumjev and hybrid closed-loop with standard insulin lispro in random order. CamAPS FX closed-loop system was used in both periods.
Results: In an intention-to-treat analysis, proportion of time sensor glucose was in target range (70 to 180mg/dL; primary endpoint) was greater with Lyumjev compared with standard insulin lispro (mean±SD; 78.7±9.8% vs. 76.2±9.6%; mean difference 2.5 percentage points [95%CI 0.8 to 4.2]; p=0.005). Mean sensor glucose was lower with Lyumjev compared with standard insulin lispro (142±14mg/dL vs. 146±16mg/dL; p=0.048). Proportion of time with sensor glucose &lt;70mg/dL was similar between interventions (median[IQR] Lyumjev 2.3% [1.3-2.7%] vs. standard insulin lispro 2.1% [1.4-3.3%]; p=0.33). No severe hypoglycemia or ketoacidosis occurred.
Conclusions: The use of Lyumjev with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with T1D.

Disclosure
M.Nwokolo: None. R.Lakshman: None. C.K.Boughton: Consultant; CamDiab Ltd., Speaker's Bureau; Ypsomed AG. J.Ware: Other Relationship; Ypsomed AG. J.M.Allen: Research Support; CamDiab Ltd. M.E.Wilinska: Consultant; CamDiab Ltd. H.Alwan: None. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. R.Hovorka: Advisory Panel; Ypsomed AG, Consultant; Abbott Diabetes, B.Braun, Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; CamDiab Ltd.

Funding
National Institute for Health and Care Research; Cambridge Biomedical Research Centre (BRC-1215-20014)
925-P: Postprandial Glucose Control Using an Extended Bolus for High Fat High Protein (HFHP) Meals during Closed-Loop (CL) in Patients with Type 1 Diabetes (T1D)
Authors: EKHLASPOUR LAYA , HOSSEINIPOUR YASAMAN J. , BUCKINGHAM BRUCE A. , CENGIZ EDA 
Published: June 2023

We investigated the impact of an extended bolus (EB) for a HFHP breakfast on postprandial glycemia in adolescents with T1D using the Control IQ (CIQ) system. In a randomized cross-over trial, following optimization, the participants with CIQ were asked to have identical standardized HFHP breakfasts (carbohydrate:51 g, fat:40 g, protein:54 g). Meal insulin bolus infusion began within 0.25 hrs of meal consumption (time 0). Eight adolescents (mean age 15.2 ± 1.7 yrs) were randomly assigned in blocks of two to the order in which they received the extended and standard insulin bolus (SB). Postprandial sensor glucose (SG) was measured for 5 hrs. The 5-hr incremental area under the curves (AUC) for SG was comparable for EB and SB (8913 and 10305 mg/dl/min, respectively). Peak SG value, time to peak SG, time in range SG (69.75% for SB vs. 71.7% for EB) and percent time &gt;180 mg/dl were similar in both groups; however, the AUC for SG 2 hrs post meal onset and the rise in SG was significantly higher with EB (p= 0.02 and 0.03 respectively). Insulin use was not significantly different between arms. CL cannot fully compensate for a HFHP meal. However, SB appears to achieve better glycemic control than EB during the two hour postprandial period. Further studies with a larger sample size and larger and longer extended meal boluses may be needed to optimize pre-meal bolus dosing for HFHP meals.

Disclosure
L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. Y.J.Hosseinipour: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. E.Cengiz: Advisory Panel; Eli Lilly and Company, Adocia, Novo Nordisk, Arecor.

Funding
National Institutes of Health (1K23DK121942)
933-P: Glycemic Level and Glycemic Variability in Acute Ischemic Stroke and Functional Outcome at Discharge—A Continuous Glucose Monitoring Study
Authors: PREECHASUK LUKANA , RILSTONE SIAN K. , XI TANG WEN , MAN JACKIE , YANG MINGMING , ZHAO ERICA , HOQUE LILY , TUNCAY ELIF , WILDING PETER , HALSE OMID , BANERJEE SOMA , OLIVER NICK , HILL NEIL E. 
Published: June 2023

Background: Glycemic variability (GV) has been associated with poor outcomes in critically ill patients. We aimed to study the association between GV and functional outcome (FO) in patients with acute ischemic stroke (AIS) using continuous glucose monitoring (CGM).
Method: Participants with AIS were enrolled and started blinded CGM (Dexcom G6) between Nov 2020 and Dec 2022. Glucose data from the first 72 hours after admission were analysed. Patients were classified into 3 groups based on change of FO (modified Rankin scale, MRS) at between admission and discharge. These included (i) remained independent (RI); (ii) deteriorated to dependent (DD); and (iii) remained dependent (RD).
Result: Sixty-seven patients (mean±SD age 72.1±13.7 years) were enrolled; 71.6% patients had no DM; 28.4% patients had DM. The median (IQR) NIHSS was 8 (3, 14), and 34.3% received reperfusion therapy. The percentage of patients with RI, DD, and RD was 25.4, 55.2, 19.4%. Patients with DD had older age, higher NIHSS at admission and at 24 hours after reperfusion therapy compared to those RI (Table). From CGM data, those with and without diabetes deteriorating to dependence had higher mean glucose and glucose SD than the group remaining independent at discharge.
Conclusion: Hyperglycemia and glucose SD are associated with deterioration of functional status at discharge after acute stroke.

Disclosure
L.Preechasuk: None. O.Halse: None. S.Banerjee: None. N.Oliver: Advisory Panel; Dexcom, Inc., Medtronic, Roche Diabetes Care, Research Support; Dexcom, Inc., Medtronic. N.E.Hill: Research Support; Dexcom, Inc. S.K.Rilstone: None. W.Tang: None. J.Man: None. M.Yang: None. E.Zhao: None. L.Hoque: None. E.Tuncay: None. P.Wilding: None.
952-P: The Accuracy and Feasibility of Continuous Glucose Monitoring in COVID-19 Non-Critically Ill Hospitalized Patients—A Pilot Study
Authors: SAKJIRAPAPONG CHOOMPUNUJ , SIRINVARAVONG SIRINART , PREECHASUK LUKANA , THONGTANG NUNTAKORN 
Published: June 2023

Background: Optimal glycemic control is associated with favorable outcomes in COVID-19 hospitalized patients. Frequent capillary blood glucose (CBG) monitoring is difficult to perform. Using continuous glucose monitoring (CGM) system to assist glycemic care can reduce the exposure of healthcare personnel and PPE usage. However, data on the accuracy of CGM in this setting are limited.
Objective: To evaluate the accuracy and feasibility of real-time CGM (rt-CGM) in non-ICU hospitalized adult COVID-19 patients.
Methods: This is a single-center prospective study of non-ICU hospitalized adult patients with COVID-19 infection who had hyperglycemia requiring insulin therapy during admission. Medtronic Guardian Connect rt-CGM sensor and transmitter were placed on the patient’s abdomen. Paired CBG and sensor glucose values were analyzed for accuracy of CGM using mean absolute relative difference (MARD) and Clarke Error Grid Analysis (CEGA).
Results: Fifteen patients were enrolled. Mean age was 48.6 ± 17.9 years. Thirteen patients (86.7%) had pre-existing diabetes. Mean HbA1c was 10.6± 3.6%. Mean duration of CGM use was 6 ± 1.2 days and mean calibration was 2.6 ± 0.7 times/day. There were 253 paired CBG and CGM measurements. The overall MARD was 9.9 ± 9.3%. The lowest MARD was observed in the CBG range of 70-180 mg/dl (9.6 ± 9.0%). The percentages of glucose readings within ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL were 80.2%, 89.7%, and 95.3%, respectively. A total of 99.2% of the data points were in zone A and B of CEGA, and none were in zone E. Percent time in range on day 1 was 57.9 ± 22.9 and improved to 64.9 ± 18.1 in the last 72 hours of sensor wear. No adverse events from the CGM were observed. CGM reduced POC testing by 30%.
Conclusions: Rt-CGM use in hospitalized patients with COVID-19 infection demonstrates high accuracy and potentially improves glucose control, reduces the frequency of CBG testing, and preserves medical resources.

Disclosure
C.Sakjirapapong: None. S.Sirinvaravong: None. L.Preechasuk: None. N.Thongtang: None.

Funding
Specific League Funds (R016421005)
958-P: Feasibility of a Long-Term Implanted Continuous Glucose Monitor (CGM)
Authors: BUTLER ANTHONY , ROBINSON LESLEY , OBEYESEKERE VARUNI R. , JONES HANNAH , KONG YEE W. , YI YUAN CHENG , BERTSCH KRISTA , ROUTH TIMOTHY L. , MARTHA SANDRA L. , TAN JASON , O'NEAL DAVID N. 
Published: June 2023

Aim: To generate pilot data regarding acceptance, safety, and function of a novel long-term CGM.
Methods: The investigational CGM (Eclipse 3, GlySens, San Diego, CA) was surgically inserted superficial to the rectus sheath in 8 type 1 diabetes adults (4 Female; Mean [SD] age 56 [7]; BMI 25 [3]). CGM data were masked to participants and processed retrospectively in simulated real-time with one capillary blood glucose calibration per day. Monthly visits evaluated: user acceptance by standardised questionnaire; health of implantation sites; safety by anti-glucose oxidase and anti-catalase antibodies; and performance benchmarked against YSI during standardised meal tests. Bluetooth communication between the sensor and an Apple iPhone was assessed continuously.
Results: One sensor was removed at 4 months (participant withdrawal) due to impacted implant environment. There were no SAE’s. User acceptance remained high for the study duration. (Figure 1) Antibody levels did not rise. The lag corrected (23.3minutes) MARD (Median [range]) of 12.4% (1401 paired readings) was stable from month 1 (13.1%) to month 10 (14.0%). CGM readings within 20/20% and 30/30% of YSI values were 85% and 96%, respectively. The App received 95% of sensor data within 10 minutes.
Conclusions: Our results provide initial data supporting participant acceptance, and safety of Eclipse 3. Further sensor refinement will reduce lag and improve performance.

Disclosure
A.Butler: Employee; GlySens Incorporated. J.Tan: None. D.N.O'neal: None. L.Robinson: None. V.R.Obeyesekere: None. H.Jones: None. Y.W.Kong: None. C.Yuan: None. K.Bertsch: Employee; GlySens Inc. T.L.Routh: Employee; GlySens Incorporated. S.L.Martha: Employee; GlySens Incorporated.