bluuebunny/crossref_metadata_2025_split huggingface dataset:
762-P: Comparing Dual-Hormone and Single-Hormone Automated Insulin Delivery System on Nocturnal Glucose Management among Pediatric People Living with Type 1 Diabetes : A Pooled Analysis
Authors: WU ZEKAI , MESSIER VIRGINIE , LEBBAR MAHA , RABASA-LHORET RÉMI 
Published: May 2022

Background: Only three studies have directly compared the efficacy of dual-hormone (DH) automated insulin delivery (AID) systems and single-hormone (SH) AID on overnight glucose management in pediatric people living with type 1 diabetes (PPWT1D) . Their conclusions differ. Pooling data could lead to stronger conclusions.
Methods: Pooled data from 3 open-label, randomized, controlled, crossover studies on comparing DH-AID and SH-AID among PPWT1D (8-17 y/o) . The primary outcome was time in range% (TIR%) overnight (00:00-06:00) based on continuous glucose monitoring. Paired t-test was applied to compare the two groups.
Results: Records from 50 PPWT1D [median (Q1-Q3) age: 14.0 years (11.8, 16.0) , mean ± SD HbA1c: 8.2 ± 0.8%] provided 246 nights of data (Table) . TIR% [ (median (IQR) ] for SH-AID and DH-AID was 91.3% (58.3, 100.0) and 94.4% (76.4, 100.0) , respectively (P=0.024) . DH-AID was superior to SH-AID in reducing time in hypo- (&lt;3.9 mmol/L) and hyperglycemia (&gt;13.9 mmol/L) but not glycemic variability.
Conclusion: DH-AID has the potential to provide better overnight glucose management than SH-AID in PPWT1D.

Disclosure
Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. M.Lebbar: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc.

Funding
Diabetes Canada grant (OG-2-12-3868-RR,OG-2-13-42P, OG-3-14-4500-RR) and Fondation JA De Sève
772-P: Combining Meal-Bolus Reduction and Exercise Announcement Eliminates the Risk of Hypoglycemia during Postprandial Exercise in People Living with Type 1 Diabetes Treated with Automated Insulin Delivery Systems
Authors: RAFFRAY MARIE , RABASA-LHORET RÉMI , MYETTE-CÔTÉ ÉTIENNE , MOLVEAU JOSÉPHINE , DEVAUX MARIE , WU ZEKAI 
Published: May 2022

For people living with type 1 diabetes (PWT1D) post-prandial exercise remains a challenge for the maintenance of glycemic control even with automated insulin delivery systems (AID) . During the postprandial phase, elevated insulin levels, rapid changes in glucose levels with increased CGM lag time make it difficult for AID algorithms to mitigate the risk of hypoglycemia by solely relying on basal rate modulation. The main objective of this study was to assess the safety and efficacy of AID using a combination strategy of pre-meal exercise announcement and meal bolus reduction during exercise bouts performed 1- and 2-hours post-meal. Thirteen adults PWT1D chronically treated with AID (6 females; A1c = 7.9 ± 0.6%; Age= 53,5 ± 15,5 years; T1D duration= 29.0 ± 16.0 years) were included. Participants performed in a randomized crossover fashion 2 60-min exercise sessions (60% of VO2peak) , 1 (60Ex) and 2-h (120Ex) post-meal. A standardized meal was given at 8AM with a 33% insulin bolus reduction and exercise was announced to the AID algorithm (target glucose increased from 6 to 9 mmol/L) up to the end of each exercise session. Plasma glucose was collected regularly. Plasma glucose times in range (3.9-10.0 mmol/L) and above range (&gt;10.0 mmol/L) from exercise onset to 90-min-post-exercise, were similar between Ex60 and Ex120 (63.7 ± 41.4% Ex60 vs. 65.9 ±24.9% Ex120, p=0.3; 36.1 ± 41.6% Ex60 vs. 34.1 ± 24.9% Ex120, p=0.4, respectively) . No hypoglycemic events (&lt;3.9 mmol/L) occurred during the study. The mean reduction in plasma glucose levels were similar during exercise in both conditions (-2.6 ± 1.4 mmol/L Ex60 vs. -3.5 ± 2.2 mmol/L Ex120, p=0.2) Conclusion: combining pre-meal exercise announcement with a meal bolus reduction of 33% was effective and safe at preventing postprandial exercise hypoglycemia in PWT1D treated with AID whether exercise was performed 1 or 2-h after a meal.

Disclosure
M.Raffray: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc. É.Myette-côté: None. J.Molveau: None. M.Devaux: None. Z.Wu: Other Relationship; Eli Lilly and Company.

Funding
National Institutes of Health (A12BC345678)
780-P: Associations between Insulin Pump Self-Management and HbA1c
Authors: RYTTER KAREN , MADSEN KRISTOFFER P. , ANDERSEN HENRIK U. , HOMMEL EVA , PEDERSEN-BJERGAARD ULRIK , SCHMIDT SIGNE , NØRGAARD KIRSTEN 
Published: May 2022

Background and Aims: It is well-known that diabetes self-management is important for glycemic outcome, also among insulin pump users. We aimed to explore which factors were independently associated with HbA1c.
Methods: Adult insulin pump users (18+) with type 1 diabetes from the Capital Region of Denmark completed an online questionnaire covering aspects of insulin pump self-management. HbA1c and demographics were collected from medical records and national registries. Backward selected linear regression models were used to investigate associations between HbA1c and each aspect of self-management, adjusted for one another, CGM/isCGM, sex, age, marital status and educational level.
Results: In total, 770 individuals responded; 60% were female, median age was 49 (p25-p75: 36-60) and ranged from 18-86 years, median HbA1c was 56mmol/mol (p25-p75: 50-62) and ranged from 25-135, and 93% used bolus calculator for meal bolus and/or correction. Self-adjustment of pump settings showed the strongest association with lower HbA1c. Avoiding missed boluses, timing of bolus insulin before meals, and timely infusion set change were also associated with a lower HbA1c. No statistically significant associations were found for HbA1c and use of advanced pump features.
Conclusion: Self-adjusting insulin pump settings, low frequency of missed meal boluses, optimal timing of meal bolus and timely change of infusion set are associated with lower HbA1c.

Disclosure
K.Rytter: Other Relationship; Medtronic, Stock/Shareholder; Novo Nordisk A/S. K.P.Madsen: None. H.U.Andersen: Advisory Panel; Abbott Diabetes, Stock/Shareholder; Novo Nordisk A/S. E.Hommel: Stock/Shareholder; Novo Nordisk A/S. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. S.Schmidt: None. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk A/S, Consultant; Novo Nordisk A/S, Research Support; Dexcom, Inc., Medtronic, Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Stock/Shareholder; Novo Nordisk A/S.
784-P: An Insulin Infusion Set with Novel Kink-Free Flexible Cannula: In-Vitro/In-Vivo Studies
Authors: CHIU CHIA , ZHANG GINA , CHATTARAJ SARNATH , GOTTLIEB REBECCA 
Published: May 2022

Objective: The wear duration of insulin infusion sets (IIS) is impacted by initial local trauma caused by cannula insertion and sustained inflammation due mostly to insulin infusion, both of which affect insulin absorption. Efforts have been made to mitigate cannula kinking at insertion and during use, and other site reactions that contribute to IIS failures. This Medtronic preclinical study investigated performance of a novel flexible and kink-free soft cannula.
Method: In-vitro tests (included buckling kink test, inflammatory macrophage cell culture, and insulin compatibility test by USP insulin monographic methods) were conducted on the Flexible cannula and commercial Teflon cannulas. In-vivo study of 3-day sets with both cannulas were conducted on diabetic swine by having animals wear one set multiple times (on the abdomen) while receiving Novolog™ insulin subcutaneously via a pump for 7 days or until set failure, determined by (1) blood glucose (BG) value not decreasing by ≥50 mg/dL an hour after a correction bolus for a BG level &gt;350 mg/dL, or (2) evidence of infection at the infusion site.
Result: Compared to the control Teflon cannula, kink resistance of the Flexible cannula was significantly improved (Kinked: Teflon 6/6, Flexible 0/6) . In the inflammatory in-vitro cell culture model, the pro-inflammatory cytokines generated by the Flexible cannula trended less (mean MCP-1: Teflon -9.7 ng/mL, Flexible - 7.7 ng/mL; mean MIP-1α: Teflon -24.1 ng/mL, Flexible - 24.0 ng/mL) . Tested by the USP methods, both cannulas were insulin compatible. In the swine diabetes model, the 3-day IIS with the Flexible cannula had a greater 7-day survival rate (50%, n=10) than the corresponding control (36%, n=56) , although not statistically different. No significant increase in total daily dose of insulin was observed.
Conclusion: Preliminary in-vitro and in-vivo test results indicate that the novel Flexible cannula is ideally suited for IIS device performance. Further product development is ongoing.

Disclosure
C.Chiu: Employee; Medtronic. G.Zhang: Employee; Medtronic. S.Chattaraj: Employee; Medtronic. R.Gottlieb: Employee; Medtronic.
786-P: Importance of Data Distribution on Deep Learning Model for Glucose Prediction
Authors: ROMERO-UGALDE HECTOR M. , ADENIS ALICE , DAUDET LAURENT , LOUIS MAXIME , TOURKI YOUSRA , HUNEKER ERIK 
Published: May 2022

Objective: This paper analyses the glycemia distribution impact in a deep learning (DL) model for glucose forecast on T1D patients.
Method: Data of 139 adult T1D patients equipped with DBLG1 System are used. Data of 70% of the patients is used for hyperoptimizing a DL model (hyperop set) and 30% for testing (test set) . The model accuracy is evaluated using the RMSE for each patient of the test set. The interquartile range (IQR) is calculated for the entire hyperop set (baseline) and for each patient. The difference between each patient IQR and the baseline is computed. Then the correlation is computed between the differences and the RMSE.
Results: A correlation of -0.77 is found between the difference of IQR and the RMSE (Figure 1 B) . It indicates that when IQR (hyperop set) &gt; IQR (patient) the prediction is more accurate. Conversely if IQR (patient) is higher, the accuracy is worse. High differences are observed between the distributions of the hyperop set and of the two patients on which the model performed worse (Figure 1 A) .
Conclusion: RMSE is larger for patients whose glycemia distribution is really different from glycemia distribution on the hyperop set. IQR difference may be used as a predictor of the prediction accuracy for a given patient.

Disclosure
H.M. Romero-Ugalde: Employee; Diabeloop SA. A. Adenis: Employee; Diabeloop SA. L. Daudet: Employee; Diabeloop SA. M. Louis: Employee; Diabeloop SA. Y. Tourki: Employee; Diabeloop SA. E. Huneker: Board Member; Diabeloop SA.
790-P: Evaluating Psychological Stress Nonglucose Signal for Incorporation in Automated Insulin Delivery System
Authors: BANERJEE AYAN , KAUR RAVINDER JEET , ZANILETTI ISABELLA , CHURCH MEI MEI , MCCRADY-SPITZER SHELLY K. , DESJARDINS DONNA , GUPTA SANDEEP , KUDVA YOGISH C. 
Published: May 2022

Introduction: Psychological stress may adversely affect glucose control. However, the effect of stress on efficacy of automated insulin delivery (AID) in Type 1 Diabetes (T1D) is still unknown. We evaluated non-glucose signals in subjects with type 1 diabetes on AID using the Empatica E4 device (E4) during psychological stress.
Method: During a 2-week prospective AID study for 12 participants with T1D, psychological stress i.e Trier Social Stress Test (TSST) was induced. Heart rate (HR) measurements using the Nonin sensor 15 mins before and after TSST confirmed psychological stress. Physical activity (PA) was analyzed and HR fluctuations coinciding with PA was rejected. The correlation of HR from E4 with the Nonin HR monitor was evaluated to explore the feasibility of using E4 HR as a substitute for Nonin HR. Pearson's moment is used to evaluate correlation.
Results: The HR from both Nonin and E4 was observed to rise after application of stress from baseline levels. The mean difference of heart rate in Nonin HR was 13.1 bpm (6 bpm) in AID and in E4 was 10.8 bpm (5 bpm) in AID. The Pearson's correlation coefficient between the Nonin and E4 HR was 0.9 in AID (p = 0.0007) . There was a trend towards increase in E4 Electrodermal activity (EDA) of normalized power spectral density (PSD) -92.5 dB/Hz (28.8) before stress to -84.9 dB/Hz (21.9) after stress in AID (p = 0.06) .
Conclusions: The E4 HR can act as a substitute to the gold standard Nonin HR. E4 HR is a good indicator of psychological stress with simultaneous analyses of accelerometry data and could be used to inform the AID controller. E4 EDA PSD is also a good indicator for stress but has a delayed response. On the other hand, HR can be affected by physical activity. Psychological stress could be detected through a fusion of E4 HR, EDA, and accelerometer sensors and incorporated into Next Gen AID for testing.

Disclosure
A.Banerjee: None. R.Kaur: None. I.Zaniletti: None. M.Church: None. S.K.Mccrady-spitzer: None. D.Desjardins: None. S.Gupta: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc., Hemsley Charitable Trust, JDRF, National Institutes of Health, Roche Diabetes Care, Tandem Diabetes Care, Inc.

Funding
JDRF grant (2-SRA-2017-503-M-B)
801-P: Effect of Adding Computerized Insulin Dose Adjustment Algorithms (CIDAA) to a Remote Patient Monitoring (RPM) Program on A1C Levels
Authors: PULICHARAM JUVAIRIYA S. , DAVIDSON JOSH , DAVIDSON MAYER B. 
Published: May 2022

The purpose of this study was to determine the effect of adding CIDAA to a subpopulation of an HMO that also had an RPM program. Patients taking insulin for &gt;6 months with A1Cs &gt;8.0% were selected from 3 cohorts, RPM + CIDAA (Group A) , RPM alone (Group B) and usual care (Group C) and followed for 6 months. Glucose readings of Group A patients, given a Bluetooth-enabled glucometer, were analyzed with dose adjustment recommendations sent to their providers (2 MDs, 1 PA) that they could accept or modify. Health educators contacted Group A and B patients for each RPM glucose value of &lt;70 or &gt;200 mg/dl and counseled them how to avoid subsequent episodes. Non-insulin drugs were not allowed to be added to Group A and B patients. A1C levels were measured at baseline and 6 months. Patient demographics, their A1C responses and alerts are shown in the Table. There were no differences among baseline A1Cs but significant differences from baseline. Groups A vs. B (P = 0.01) and A vs. C (P = 0.001) were significantly different but not B vs. C. All alerts (P = 0.02) and those &gt;200 mg/dl (P = 0.002) were significantly less in Group A vs. B but alerts &lt;70 mg/dl were not. Conclusion: A1C levels fell twice as much without increases in hypoglycemia in poorly controlled type 2 diabetic patients taking insulin whose providers received recommendations for dose changes based on CIDAA every 2-3 weeks compared with RPM alone or usual care.

Disclosure
J.S.Pulicharam: None. J.Davidson: None. M.B.Davidson: Other Relationship; Mellitus Health.

Funding
Mellitus Health, Inc
802-P: Safety, Pharmacokinetics, and Pharmacodynamics of Once-Weekly Basal Insulin Fc (BIF) in Japanese Patients with Type 2 Diabetes: A Phase 1 Open-Label, Randomized, Active-Controlled Trial
Authors: NASU RISA , OURA TOMONORI , OHWAKI KENJI , IMORI MAKOTO , FURIHATA KENICHI 
Published: May 2022

The aim was to investigate the safety, pharmacokinetics (PK) , and pharmacodynamics (PD) of once-weekly Basal Insulin Fc (BIF) , a novel long-acting IgG Fc-fusion protein being developed for the treatment of diabetes. This multiple-site, open-label, randomized, active-controlled, multiple-dose Phase 1 study investigated individualized weekly subcutaneous injections of BIF compared to once-daily insulin degludec over 6 weeks in Japanese patients with T2D on stable doses of basal insulin, with or without antihyperglycemic medication. In a 5-week lead-in period to treatment, all patients titrated insulin degludec to a fasting glucose (FG) target of 100 to 139 mg/dL. Outcomes included safety (primary) and PK and PD (secondary) . ClinicalTrials.gov NCT04276428. Patients were randomized to receive BIF (n=18) or insulin degludec (n=10) . TEAE incidence was low for both BIF (n=4; 22.2%) and insulin degludec (n=2; 20.0%) . All TEAEs were mild, nonserious, and unrelated to BIF. A total of 6 (33.3%) and 2 (20.0%) patients reported hypoglycemic events during BIF and insulin degludec treatment, respectively, none of which were severe. Median tmax was 3 or 4 days. Geometric mean t1/2 of BIF was 15 days. The peak to trough ratio (Cmax to 168 hours postdose concentration after final dose at Week 6) was 1.13. Mean FG was statistically significantly increased from baseline from Weeks 3 to 7 following first dose of insulin degludec but was not increased with BIF (LS means [SE] change: Week 3 BIF, -6.6 [4.7]; degludec, 22.1 [5.9]; Week 7 BIF, -3.5 [7.1]; degludec, 25.3 [9.3] mg/dL) . The 7-point SMPG profile was unchanged with BIF over treatment. In Japanese patients with T2D, once-weekly BIF was well tolerated and associated with prolonged PK and improved glycemic control. PK/PD profiles in Japanese patients are consistent with prior studies and support participation in Phase 3 studies.

Disclosure
R. Nasu: None. T. Oura: Employee; Eli Lilly Japan K.K. Stock/Shareholder; Eli Lilly and Company. K. Ohwaki: None. M. Imori: Employee; Eli Lilly Japan K.K. K. Furihata: Other Relationship; Eli Lilly and Company, Pfizer Japan Inc.

Funding
Eli Lilly Japan K.K.
805-P: Sarcopenia in Insulin-Treated Older Adult Patients with Type 2 Diabetes
Authors: LEITE SILMARA A.O. , BASTOS MURILO , SILVA MICHAEL , LAVALLE ANA C.R. , BERTOGY MARIA C. , VIEIRA SUELEN C. , UMPIERREZ GUILLERMO E. 
Published: May 2022

Background: The relationship of sarcopenia with relevant features of T2D and its treatment are inconsistent in the literature.
Aims: To evaluate the prevalence of sarcopenia in insulin treated older adults with T2DM.
Methods: This is a cross sectional data from a prospective observational cohort study that evaluated subjects older than 65 y/o with T2D on insulin therapy, with or without oral agents, and HbA1c between 7% and 9%, identified from a public hospital and a private diabetes clinic and invited by phone to participate (n= 462) . Patients treated with GLP1 agonists; eGFR &lt;30 ml/min; Hb &lt;11g/dL; ALT&gt; 3x ULN; glucocorticoid use in the previous 3 months, and active malignancy were excluded. The diagnosis of sarcopenia was based on the European Working Group on Sarcopenia in Older People (EWGSOP2) . The SARC-F questionnaire was applied and considered high risk if score &gt; 4. Muscle strength was assessed by handgrip strength (HS) using a manual dynamometer (Jamar®) . The muscle mass was assessed by electrical bioimpedance (BIA - Inbody®) obtaining the skeletal muscle mass index (SMI = MM appendicular / height2) . The physical performance was assessed by the timed up-and-go test (TUG) . The presence of sarcopenia was considered when HS &lt;16Kg for women and &lt;27Kg for men and confirmed when SMI &lt;7.00 kg /m2 for men and ≤5.50 kg / m2 for women. The severity was evaluated when TUG was ≥20s.
Results: We assessed 125 patients aged 72.8 ± 5.8 y/o, 53% women and T2D median duration of 21 years (min 1; max 47) ; HbA1c=8.5 ± 1,5%. 50,5% of patients had macrovascular complications history; 25.8% retinopathy; 48,3% neuropathy and 14,3% nephropathy. 18,8% had SARC-F score &gt; 4 indicating high risk of sarcopenia. However, the clinical tests confirmed sarcopenia in only 1,6% of the participants.
Conclusions: The prevalence of sarcopenia in older adults with T2D on insulin treatment was lower than general population, which may be explained by the insulin anabolic effects.

Disclosure
S.A.O.Leite: None. M.Bastos: None. M.Silva: None. A.C.R.Lavalle: None. M.C.Bertogy: None. S.C.Vieira: None. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk.

Funding
Abbott Diabetes Care ADC-OUS-IIS-19-47
811-P: Efficacy and Safety of Ultrarapid Lispro (URLi) vs. Humalog (Lispro) in Chinese Pediatric Patients with Type 1 Diabetes (T1D) : A Subpopulation Analysis of PRONTO-Peds Study
Authors: GU WEI , YANG YUXIN , YUAN YUAN , LUO FEIHONG 
Published: May 2022

URLi is a novel formulation of insulin lispro developed to better mimic the physiological glucose response postmeal. This analysis was to evaluate URLi vs. lispro in Chinese subpopulation from a phase 3 global study (PRONTO-Peds) in pediatric patients with T1D. Chinese patients were randomized to double-blind mealtime URLi (n=7) , lispro (n=11) , or open-label URLi dosed up to 20 minutes postmeal (URLi+20; n=4) . The primary endpoint was the difference between URLi and lispro in HbA1c change from baseline to Week 26, with the difference between URLi+20 and lispro in HbA1c change being also assessed. The mixed-effect model repeated measure model was used for analyzing the primary endpoint. Same trend in the treatment difference in HbA1c change from baseline to Week 26 was observed in Chinese patients as the overall population (URLi minus lispro: -0.09% vs. -0.02%; URLi+20 minus lispro: -0.31% vs. -0.02%) , with HbA1c increases in URLi, lispro, and URLi+20 groups by 1.06%, 1.15%, and 0.85%, respectively. In Chinese patients, the premeal to 1-hour postmeal daily mean glucose excursion was numerically lower with URLi (-31.1 mg/dL) than with lispro (15.3 mg/dL) or with URLi+20 (39.2 mg/dL) at Week 26. No clinically meaningful treatment differences were observed at baseline and Week 26 for basal, bolus, and total insulin dose. No death, serious adverse events including severe hypoglycemia, discontinuations due to adverse events, and treatment-emergent injection site reactions occurred. At Weeks 0 to 26, the rate of all documented hypoglycemia and documented hypoglycemia at ≤4 h and &gt;4 h postdose for blood glucose ≤70 mg/dL showed numerically greater decrease from baseline with URLi and URLi+20 than with lispro. Overall, mealtime and postmeal URLi vs. lispro demonstrated same trend in the glycemic control as assessed by HbA1c in Chinese pediatric patients with T1D as the overall population and a similar safety profile.

Disclosure
W.Gu: None. Y.Yang: Employee; Eli Lilly and Company. Y.Yuan: None. F.Luo: None.

Funding
Eli Lilly and Company