bluuebunny/crossref_metadata_2025_split huggingface dataset:
764-P: A Random-Order, Double-Blinded, Placebo-Controlled Study of the Bionic Pancreas in the Bihormonal vs. the Insulin-Only Configuration Using Two Different Glucose Targets in Adults with Type 1 Diabetes in a Standardized Exercise Setting
Authors: CASTELLANOS LUZ E. , BALLIRO COURTNEY A. , SHERWOOD JORDAN , HILLARD MALLORY , SELAGAMSETTY RAJENDRANATH , ZHENG HUI , EL-KHATIB FIRAS , DAMIANO EDWARD , RUSSELL STEVEN J. 
Published: May 2022

Objective: We evaluated glycemic outcomes at two glucose targets with each of two configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in the setting of standardized exercise in adults with type 1 diabetes.
Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo) , random-order, cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using two glucose targets (1 and 130 mg/dl) ; each arm lasted three days. On the last morning of each arm, fasted subjects exercised on a stationary bike with a heart rate of 120-140 bpm for ∼30 minutes. The primary outcome was number of subjects discordant between the BH and IO arms using the same glucose target for events with plasma glucose (PG) &lt;60 mg/dl for more than minutes (McNemar's Test) . Secondary endpoints included the area over the glucose curve and &lt;60 mg/dl and grams of carbohydrates given for hypoglycemic events (Wilcoxon Signed Rank Test) .
Results: When using the 130 mg/dl glucose target, there were no events with PG&lt;60 mg/dl in either the BH or IO configurations; AOC &lt;60 mg/dl was 0 min*mg/dl for both configurations and no carbohydrates were given. When using the 1mg/dl glucose target, three subjects in the IO arm had an event with a PG &lt;60 mg/dl for more than minutes; no subjects had an event using the BH configuration (p=0.25) . Median AOC &lt;60 mg/dl was 0 [0-0] min*mg/dl for both configurations (p=0.18) , and the median amount of carbohydrates required to recover from hypoglycemic events was 0 [0-0] grams for both configurations (p=0.56) .
Conclusions: Both configurations of the BP provided safe glycemic regulation using both glucose targets during exercise use. Larger studies will be needed to quantify differences in exercise outcomes between the IO and BH configurations of the BP.

Disclosure
L.E.Castellanos: None. C.A.Balliro: Consultant; Beta Bionics, Inc., Zealand Pharma A/S. J.Sherwood: None. M.Hillard: None. R.Selagamsetty: Employee; Beta Bionics, Inc. H.Zheng: None. F.El-khatib: Employee; Beta Bionics, Inc., Stock/Shareholder; Beta Bionics, Inc. E.Damiano: Other Relationship; Beta Bionics, Inc. S.J.Russell: Advisory Panel; ConvaTec Inc., Eli Lilly and Company, Consultant; Beta Bionics, Inc., Other Relationship; Beta Bionics, Inc., Research Support; Beta Bionics, Inc., Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Companion Medical.

Funding
NIDDK (T32DK007028)
781-P: Progressive Acceleration of Insulin Exposure over Seven Days of Infusion Set Wear
Authors: BAILEY TIMOTHY S. , KASTNER JASMIN R. , STRANGE POUL , SHI LEI , OBERG KEITH A. , JOSEPH JEFFREY I. , STRASMA PAUL J. , MUCHMORE DOUGLAS B. 
Published: May 2022

Insulin exposure and action are known to differ on each of 3 days of infusion set wear during CSII. We extend these observations to 1 week in a pilot phase study comparing conventional Teflon angled infusion sets to a prototype extended wear set using Capillary Biomedical SteadiFlow™ technology. Participants with T1DM for &gt;12 months, A1C &lt;8.5%, c-peptide &lt;0.6 nmol/L, and ≥6 months use of Medtronic model 530G or higher were enrolled in a 2-period crossover euglycemic clamp study; clamps were performed after fasting overnight stabilization with IV insulin. Five men and 2 women, mean duration of diabetes 22.5 (16.6 SD) years and mean BMI 27.6 (3.8 SD) kg/m2 were enrolled; 4 completed all 8 clamps, 2 completed 7 clamps and 1 completed 1 clamp. We present the pharmacokinetic profiles of insulin lispro, 0.15 U/kg delivered by bolus infusion on Days 0, 3, 5 and 7 of infusion set wear. The Figure shows aggregate results from Control and Investigational infusion sets for insulin concentration (mean±SEM) vs. time by day of set wear. Statistically significant decreases from Day 0 to Day 7 were seen for tmax (p≤0.001) , t50% (early) (p&lt;0.002) , t50% (late) (p&lt;0.001) , and Mean Residence Time (p&lt;0.001) . AUC0-300 declined by approximately 20% from Day 0 to Day 7 (p&lt;0.11) . These results confirm and extend previous observations showing significant progressive acceleration of insulin exposure as a function of duration of infusion set wear time.

Disclosure
T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. J.R.Kastner: Consultant; Capillary Biomedical, Inc. P.Strange: Other Relationship; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. L.Shi: None. K.A.Oberg: Consultant; Beta Bionics, Inc., Companion Medical, Tandem Diabetes Care, Inc. J.I.Joseph: Advisory Panel; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. P.J.Strasma: Board Member; Capillary Biomedical, Inc., Employee; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. D.B.Muchmore: Consultant; Capillary Biomedical, Inc., Diasome, Zucara Therapeutics, Stock/Shareholder; Capillary Biomedical, Inc., Diasome.

Funding
National Institutes of Health (2R44DK110969-02)
79-LB: The Effects of Glucose Reporting Tools on Therapeutic Decision Making—A Comparative Reading Study with Primary Care Providers
Authors: NOVAK MATTHEW T. , HAYTER GARY , WRIGHT EUGENE , MIDYETT KURT , WOLPERT HOWARD , VIRDI NAUNIHAL 
Published: May 2022

The discordance between the amount of new therapies for Type 2 diabetes (T2D) and improved outcomes highlights an unmet need for tools to help primary care providers (PCPs) make appropriate therapy adjustments. Here we present a novel CGM-based Glucose Pattern Insights Report (GPIR) that identifies patterns of suboptimal glycemic control, highlights the clinically most important pattern (MIP) , and offers therapy recommendations to address the MIP. To assess utility of the GPIR in clinical decision making, a reading study was conducted comparing it against a current standardized glucose report (SGR) . Clinical data from ten T2D subjects were used to generate complementary GPIRs and SGRs. Non-specialist PCPs (n=35) evaluated each case in each report design alongside A1c and medication regimen to make a therapy change recommendation. The study was structured as a two-round, full crossover session. Each round contained all ten cases for a given report design. PCPs were randomized to determine the initial report design presented. Therapy change recommendations were categorized by whether they addressed the MIP present, with a priority on treating hypoglycemia if it occurs coincident with other patterns within a given case. PCPs addressed the MIP equally well with each report in cases presenting patterns other than hypoglycemia. Across all cases and all subjects, therapy change categorizations were different in 79 instances with sixty-seven of these instances presenting hypoglycemia (ie: a PCP recommendation using one report addressed hypoglycemia, while that using the other report did not) . Within this subset, in all but one instance (66 of 67; 99%) PCPs correctly addressed low glucose with the GPIR when they did not for the same case using the SGR. These findings indicate the GPIR aides in identification and treatment of hypoglycemia that would otherwise be missed using current standardized reports.

Disclosure
M. T. Novak: Employee; Abbott Diabetes. G. Hayter: n/a. E. Wright: Advisory Panel; Abbott Diabetes, Bayer AG, Boehringer Ingelheim International GmbH, Gelesis, GlaxoSmithKline plc., Lilly Diabetes, MannKind Corporation, Medtronic, Sanofi-Aventis U. S., Consultant; Abbott Diabetes, Bayer AG, Bigfoot Biomedical, Inc., Boehringer Ingelheim International GmbH, Lilly Diabetes, Stability Health, Other Relationship; UpToDate, Speaker’s Bureau; Abbott Diabetes, American Diabetes Association, Bayer AG, Boehringer Ingelheim International GmbH, Sanofi-Aventis U. S. K. Midyett: Consultant; Abbott Diabetes. H. Wolpert: Employee; Lilly Diabetes. N. Virdi: Employee; Abbott Diabetes.
806-P: Correlation of Derived Time in Range (dTIR) and Time in Range (TIR) in People with Type 2 Diabetes (T2D) Treated with IDegLira (IDL) , Degludec, or Liraglutide: A Post Hoc Analysis of the DUAL I Trial
Authors: PHILIS-TSIMIKAS ATHENA , DCRUZ JOHN M. , SIVARATHINASAMI RAMSATHISH , DE BLOCK CHRISTOPHE 
Published: May 2022

Background and Aims: TIR (blood glucose 70-180 mg/dL) , measured by continuous glucose monitoring (CGM) , provides a more comprehensive picture of glycemic control than A1c alone. Derived TIR (dTIR) , a calculated estimate of TIR, is useful when CGM data are unavailable. This post hoc analysis of DUAL I investigated the correlation between dTIR and TIR in patients with CGM data.
Materials and Methods: In DUAL I, people with T2D uncontrolled on oral antidiabetic drugs (n=1663) were randomized 2:1:1 to IDL, degludec or liraglutide, for up to 52 weeks. CGM data were collected using IPro1 and IPro2 (Medtronic) . dTIR was calculated from 9-point self-measured blood glucose (SMBG) profiles (minimum 6 points) . The Pearson correlation coefficient was used to assess correlation between dTIR and TIR at baseline, and at weeks 26 and 52. Also assessed were the correlation between change in dTIR and change in TIR, from baseline to end of trial (EOT) , and the proportion of patients achieving a ≥5% increase in TIR or dTIR at weeks 26 and 52.
Results: 260 patients had CGM data. Using dTIR calculated from patients with ≥6-point SMBG profiles, a strong correlation was seen between dTIR and TIR at baseline (n=2observations; correlation 0.8838) , with a moderate correlation also seen at week 26 (n=165; correlation 0.5512) and week 52 (n=152; correlation 0.5184) . Change in dTIR and change in TIR, from baseline to EOT, were also correlated (n=137; correlation 0.7686) . Similar results were seen using dTIR calculated using ≥7- or ≥8-point SMBG profiles. A numerically greater proportion of patients achieved a ≥5% increase in dTIR vs. TIR at weeks 26 and 52 (78% vs. 54% and 62% vs. 50%, respectively) , perhaps due to missed nocturnal hypoglycemia, and limited data points, measured by SMBG.
Conclusion: These data support the use of dTIR as a surrogate endpoint when CGM data are unavailable, to provide additional information on glycemic control.

Disclosure
A.Philis-tsimikas: Advisory Panel; Bayer AG, Novo Nordisk, Research Support; Lilly Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Viking Therapeutics. J.M.Dcruz: Employee; Novo Nordisk Global Business Services. R.Sivarathinasami: None. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.

Funding
Novo Nordisk A/S
823-P: The Long-Acting Dual Amylin and Calcitonin Receptor Agonist KBP Has Increased Efficacy on Weight Loss and Glucose Control Compared with Cagrilintide in Obese and Diabetic Rats
Authors: LARSEN ANNA T. , SONNE NINA , MOHAMED KHALED ELHADY , BREDTOFT EMMA-MARIE , ANDERSEN FREDERIK , KARSDAL MORTEN A. , HENRIKSEN KIM 
Published: May 2022

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes (T2D) and obesity due to their beneficial effects on both body weight, glucose control and insulin action. Cagrilintide, which is currently in clinical trials, has shown promising effects on weight loss. In this study we compared a new long-acting DACRA (KBP) to cagrilintide in pre-clinical models of obesity and T2D. In vitro potencies were assessed using receptor assays. In vivo efficacies were investigated head-to-head in high fat diet (HFD) fed obese and T2D (ZDF) rat models. In vitro data showed that both peptides active both the amylin and the calcitonin receptor, with KBP being more potent on both receptors. This was further confirmed in vivo by assessment of acute effects on food intake and CTX suppression. KBP (1.5, 4.5 and 13.5 nmol/kg) and cagrilintide (10, 30 and 100 nmol/kg) induced a potent and dose-dependent weight loss in HFD rats, with the highest dose of KBP being superior to cagrilintide. In diabetic ZDF rats, DACRA treatment improved glucose control and preserved plasma insulin compared to vehicle. Interestingly, despite similar levels of plasma insulin, KBP treatment was superior to cagrilintide in improving glucose control. This was further reflected in the HbA1c levels at study end, where KBP treatment resulted in significantly lower levels compared to cagrilintide.
In summary, both DACRAs induced weight loss and improved glucose tolerance, insulin action as well as glucose control. However, KBP treatment results in superior efficacy on both weight loss and glucose control. These findings highlight KBP as a promising once-weekly agent for treatment of obesity and T2D.

Disclosure
A.T.Larsen: Employee; Nordic Bioscience. N.Sonne: None. K.Mohamed: None. E.Bredtoft: None. F.Andersen: None. M.A.Karsdal: Employee; Nordic Bioscience A/S, Nordic Bioscience A/S, Nordic Bioscience A/S. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.
845-P: Advancing Therapy in Basal Insulin–Treated Type 2 Diabetes: Exploratory Analysis of the SoliMix Trial by Baseline HbA1c, Insulin Dose, and BMI
Authors: HOME PHILIP , MCCRIMMON RORY J. , ROSENSTOCK JULIO , BLÜHER MATTHIAS , PEGELOW KATRIN , MELAS-MELT LYDIE , DJABALLAH KHIER , GIORGINO FRANCESCO 
Published: May 2022

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk requiring less insulin with once-daily iGlarLixi vs. twice-daily premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) and oral antihyperglycemic drugs (OADs) .
Methods: Adults with T2D and HbA1c 7.5-% on BI + 1-2 OADs were randomized to iGlarLixi or BIAsp 30 for 26 weeks. Primary outcomes were non-inferiority in HbA1c change or superiority in body weight change with iGlarLixi vs. BIAsp 30. This post hoc analysis assessed SoliMix endpoints by baseline HbA1c (7.5-8, &gt;8-9, &gt;9-%) , insulin dose (&lt;30, ≥30 U/day) , and BMI (&lt;25, ≥25-&lt;30, ≥30-&lt;35, ≥35 kg/m2) .
Results: No differences in treatment effect were seen across subgroups for change in HbA1c or BMI (heterogeneity p&gt;0.10; Table) ; both primary objectives were met in the HbA1c &gt;8-≤9 %, BMI ≥25-&lt;30 kg/m2, and insulin dose subgroups. No differences in treatment effect were seen across subgroups for the lesser insulin dose increments with iGlarLixi vs. BIAsp 30 (p&gt;0.10) . Level 2 hypoglycemia incidence and rates were unaffected by baseline HbA1c and BMI (p&gt;0.10) , but p&lt;0.for events by insulin dose.
Conclusions: Primary SoliMix findings for iGlarLixi vs. BIAsp 30 were consistent across baseline HbA1c and BMI subgroups but inconsistent for baseline insulin dose.

Disclosure
P.Home: Advisory Panel; Kriya Therapeutics, Consultant; Mundipharma, Sanofi, Other Relationship; AstraZeneca, Sanofi, Research Support; Gan & Lee Pharmaceuticals, Sanofi, Speaker's Bureau; Gan & Lee Pharmaceuticals, Medscape. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH. L.Melas-melt: None. K.Djaballah: Employee; Sanofi. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited.

Funding
Sanofi
848-P: Efficacy and Safety of GlucoLo Plus in Type 2 Diabetes Management
Authors: ZARRUK ALEXANDRO R. 
Published: May 2022

Background and Aims: Diabetes is globally increasing in prevalence and patients are constantly on the lookout for Complementary and Alternative Medicines (CAM) that are safe and efficacious including biologically-based practices such as vitamins and dietary supplements.
Methods: This double-blind randomised placebo-controlled trial evaluated the effects of daily GlucoLo Plus, a newly formulated biologically-based CAM for diabetes type 2 management. The primary outcome was to evaluate the effect of GlucoLo Plus on HbA1c and the secondary outcomes were to assess its effect on fasting glycemia, lipid profile, weight and assess its safety profile.
Results: Of 64 individuals assessed for eligibility, 60 (mean HbA1c 6.98% [52.8 mmol/mol], mean age 67.3 years [SD 9.5], 26 [43%] women, mean diabetes duration 3.2 years, and mean body mass index 27.9 kg/m2) were randomly assigned to GlucoLo Plus (n=32 [53%]) , or placebo (n=28 [47%]) . At 12 weeks, GlucoLo Plus decreased HBA1c by 0.843% (P=0.0121) while placebo reduced it by 0.132% (p = 0.5951) . GlucoLo Plus was also associated with non-significant reduction in fasting glycemia, total cholesterol, triglyceride, and LDL-cholesterol. GlucoLo Plus arm had a mean 1.84 lbs weight loss while the placebo arm had a 0.21 lbs weight gain. The most frequent adverse events with GlucoLo Plus were mild and transient gastrointestinal events including nausea (9.3% vs. 3.5%) and dyspepsia (15.6% vs. 10.7%) .
Conclusion: GlucoLo Plus significantly lowered HbA1c and had positive effect on bodyweight, fasting glycemia, LDL-cholesterol and had a minimal side effect profile. These results suggest that GlucoLo Plus could be an alternative and adjunct to type 2 diabetes management in people who are reluctant to initiate or add new antidiabetic agents.

Disclosure
A.R.Zarruk: Advisory Panel; Amgen Canada, AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eisai Inc., Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc., Sanofi, Takeda Canada, Valeant Pharmaceuticals, Other Relationship; Groupe Nature Pharma, Research Support; Abbott Diabetes, Novo Nordisk Canada Inc., Orimed Pharma, Speaker's Bureau; Abbott, Abbott Diabetes, Amgen Canada, AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Mylan N.V., Novo Nordisk Canada Inc., Orimex Pharma, Sanofi, Takeda Canada, Valeant Pharmaceuticals, Viatris Inc.

Funding
Groupe Nature Pharma
85-OR: Thalamic H1-MRS Metabolite Parameters Are Related to Mood Disorders in Type 1 Diabetes
Authors: GREIG MARNI , SLOAN GORDON P. , SHILLO PALLAI RAPPAI , SELVARAJAH DINESH , WILKINSON IAIN D. , TESFAYE SOLOMON 
Published: May 2022

Objective: We have previously demonstrated increased thalamic blood volume and preserved HMRS neuronal metabolite ratios in painful diabetic peripheral neuropathy (P-DPN) . We hypothesised that perfusion measures and neuronal function measured by metabolite ratios may be related. However, as brain metabolite ratios may also be affected by mood disorders, common in P-DPN, this may be a significant confounding factor.
Methods: 52 type 1 diabetes (T1D) subjects (18 P-DPN, 23 DPN, 13 without neuropathy-DM-NN) and 18 healthy volunteers (HV) were recruited. 1HMRS was performed at 3T (Philips, Netherlands) . Single voxel spectra were obtained from a 2.25cm3 (15x10x15mm) volume of interest within the thalamus, TE=135ms, TR=1600ms, NSA=256 using point resolved (PRESS) technique. Metabolite ratios were calculated for choline, Creatine, and N-Acetyl Aspartate (NAA) . MR-DSC images were obtained at 3T using a T2*-weighted technique (TR/TE=1250/35ms; 72 dynamics) to assess the passage of bolus intravenous gadolinium-chelate through the thalamus.
Results: There was significant negative correlation between NAA/Cr (measure of neuronal function) and measures of depression: Hospital Anxiety and Depression Scale R= -0.33 (p=0.01) , Becks Depression Inventory R= -0.25 (p=.048) ; and anxiety: State-Trait Anxiety inventory- State (STAI-S) R= -.37 (p=.002) , STAI- Trait (T) R= -.32 (p=0.01) and Behavioural Inhibition R= -0.25 (p=0.04) . There were no differences in metabolite ratios between groups; and no significant correlations between perfusion measures and metabolite ratios.
Conclusion: This is the first study to show thalamic 1HMRS metabolite ratios are correlated with measures of mood disorders in T1D. The high prevalence of mood disorders in P-DPN and DPN have confounded previous 1HMRS studies and may explain conflicting reports in the literature. The link between neuropathy and mood disorders needs further exploration to understand whether both may arise from a common neurobiological pathway.

Disclosure
M.Greig: None. G.P.Sloan: None. P.Shillo: None. D.Selvarajah: None. I.D.Wilkinson: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc.

Funding
European Foundation for the Study of Diabetes (EFSD)