bluuebunny/crossref_metadata_2025_split huggingface dataset:
552-P: Impact of Stakeholder Engagement in Pediatric Type 1 Diabetes (T1D): Experience from the T1D High-Fidelity Wraparound Program (HFWP)
Authors: NEVIN AMY G. , MARCH CHRISTINE , JONES LAUREN , SCHREIBER JUSTIN , LIBMAN INGRID 
Published: June 2021

Despite recent advances, management of pediatric T1D remains extremely challenging, in part due to psychological distress and poor adherence to recommendations. The HFWP aims to adapt and test an innovative strategy, used in behavioral health, to improve self-management and self-efficacy in high-risk youth with T1D. Stakeholder engagement, with the integration of patient, family and community/system partners into the research team, is increasingly recognized as a critical component of patient-centered research. We describe the process and outcomes of stakeholder engagement to inform T1D HFWP research activities and resources. A total of 21 stakeholders, representing family, youth and community/systems partners (e.g., ADA, JDRF, Health Plan), were selected through a rigorous application process and participated in monthly meetings for 13 months. Measures of satisfaction with processes and experience were obtained via an anonymous survey completed after every meeting. On average, 70% consistently answered the survey over 13 months. Stakeholders strongly agreed that the meetings met their expectations (4.75/5), objectives were identified and followed (4.5/5), their voices were heard (4.64/5) and the Advisory Board was effectively molding the T1D HFWP (4.75/5). The majority (~70%) were satisfied with meeting frequency and duration. The Advisory Board proposed important outcome measures which were adopted, including evaluation of anxiety and distress in youth and caregivers. Concrete areas of need were identified, leading to systematic development of tools, including a guide for families to vet online T1D resources and design of a practical, patient-centered form outlining a medical summary for families (e.g., insurance, type of devices used, phone numbers, etc.). This experience illustrates the willingness and importance of partnering with stakeholders to help shape resources and programs in pediatric T1D intervention research.

Disclosure
A. G. Nevin: None. C. March: None. L. Jones: None. J. Schreiber: None. I. Libman: Advisory Panel; Self; Novo Nordisk.

Funding
Children’s Hospital of Pittsburgh Foundation
554-P: Diabetes Distress in Young Adults with Youth-Onset Type 2 Diabetes: TODAY Study Results
Authors: TRIEF PAULA M. , WEINSTOCK RUTH S. , USCHNER DIANE , TUNG MELINDA , CHAO LILY , FARRELL RYAN M. , KEADY JOYCE , MACLEISH SARAH A. , MARCUS MARSHA D. , RAYAS MARIA S. 
Published: June 2021

Aims: Diabetes distress (DD) is associated with poor health outcomes. Little is known about level of DD in young adults (YAs) with youth-onset type 2 diabetes (T2D) or individual factors associated with DD. Aims were to assess level of DD, and factors associated with high DD, in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort.
Methods: YAs completed the Diabetes Distress Scale (DDS), PHQ-9 (depressive symptoms) and GAD7 (anxiety), at the end-of-study visit. Factors that may relate to DD were demographics (sex, race/ethnicity, age, education, income), medical history (HbA1c, BMI, complications), and social/economic factors (# persons in household, parent status, healthcare coverage, access to diabetes care provider). Univariate logistic regressions found factors associated with high DD. Multivariate regression controlled for sex, HbA1c, healthcare coverage, anxiety, depressive symptoms and retinopathy.
Results: Of 457 YAs, mean age=26.7 yrs, 65% were female, 20% non-Hispanic white, 38% non-Hispanic Black, 20% Hispanic, 62% &lt;$25K income. High DD (DDS ≥2) was reported by 108 (23.6%). Subscales found 39.8% with high “regimen distress,” 29.8% with high “emotional burden” (29.8%). Unadjusted results: Sex (p=0.001), HbA1c (p&lt;0.0001), no healthcare coverage (p=0.043), hypertension (p=0.036) and retinopathy (p=0.005) were associated with DD. Moderate-severe depressive symptoms (PHQ-9 ≥10) and anxiety (GAD≥5) were also associated with DD (p&lt;0.0001). In multivariate analyses, female sex, anxiety, HbA1c (p&lt;0.0001 for all), and no healthcare coverage (p=0.022) remained associated with DD. Individual microvascular complications, BMI, depressive symptoms, race/ethnicity, age, education, income, # persons in household, or having a diabetes care provider did not relate to adjusted DD.
Conclusion: In young adults with youth-onset T2D, high DD was significantly more likely in females, and those with anxiety, high HbA1c, and without healthcare coverage.

Disclosure
P. M. Trief: None. M. S. Rayas: Research Support; Self; National Center for Advancing Translational Sciences. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. D. Uschner: None. M. Tung: None. L. Chao: None. R. M. Farrell: Stock/Shareholder; Self; Tandem Diabetes Care. J. Keady: None. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. M. D. Marcus: Advisory Panel; Self; Weight Watchers International, Inc.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212, U01DK61230, U01DK61239, U01DK61242, U01DK61254)
591-P: Glucose Dynamics during OGTT Identify Metabolic Subphenotypes in Individuals with Glucose Dysregulation
Authors: METWALLY AHMED A. , PERELMAN DALIA , PARK HEYJUN , CELLI ALESSANDRA , MCLAUGHLIN TRACEY , SNYDER MICHAEL 
Published: June 2021

Type 2 diabetes (T2D) is a heterogeneous disorder, with a complex physiologic basis. Muscle insulin resistance, beta-cell dysfunction, and impaired incretin effect may be present to differing degrees. Identifying the underlying physiology of glucose dysregulation in a given individual would allow for tailored treatment. We hypothesized that glucose dynamics (i.e., glucotypes) during a frequently-sampled 3-hour OGTT could identify the underlying pathophysiology of glucose dysregulation. If true, glucotypes from OGTT and/or continuous glucose monitoring devices may extend current diagnostic approaches for T2D by defining the dominant metabolic subphenotype.
A total of 33 participants underwent gold-standard metabolic tests including: OGTT with blood sampled every 5-10 min for 180 min with c-peptide deconvolution, isoglycemic intravenous glucose infusion (IIGI), and modified insulin suppression test (IST), to quantify beta-cell function, incretin effect, and insulin resistance. Glucotypes were constructed from a time series with glucose values from the OGTT. Missing timepoints were imputed using cubic smoothing splines. Each series was Z-normalized to focus on the shape of the curve rather than the amplitude. Singular value decomposition was performed and the first two principal components were used in cluster analysis, and related to gold-standard metabolic tests.
Cluster analysis of glucose dynamics variables revealed 2 separable clusters identifying individuals classified as insulin resistant or sensitive based on IST. Beta-cell dysfunction was also distinguishable by cluster analysis. Although impaired incretin effect status was identified using the deconvolution of the c-peptide from the OGTT and IISI, it was not clearly separable through glucotypes.
Glucotypes may be used to identify metabolic subphenotypes in glucose-dysregulated states, with the potential to personalize treatment approaches that address the dominant physiologic defect.

Disclosure
A. A. Metwally: None. D. Perelman: None. H. Park: None. A. Celli: None. T. Mclaughlin: Board Member; Self; January, Inc. M. Snyder: Research Support; Self; Fitbit, Inc., Stock/Shareholder; Self; January, Inc., Qbio.

Funding
National Institutes of Health (5R01DK110186-02); Precision Health and Integrated Diagnostics Center at Stanford
626-P: Intermittently Scanned Continuous Glucose Monitoring Data of Polish Patients from Real-Life Conditions: More Scanning and Better Glycemic Control than Worldwide
Authors: HOHENDORFF JERZY , GUMPRECHT JANUSZ , MYSLIWIEC MALGORZATA , ZOZULINSKA-ZIOLKIEWICZ DOROTA , MALECKI MACIEJ 
Published: June 2021

Randomized trials and observational studies have shown that the use of FreeStyle Libre® intermittently-scanned CGMS was associated with improved glycemic indices such as HbA1c, TIR (70-180 mg/dl), TBR (&lt;70 mg/dl) or TAR (&gt;180 mg/dl), and improved quality of life. In this RWD analysis, we aimed to describe glucometrics among FreeStyle Libre users from Poland and compare them with international data. The analyzed time period for the Polish and worldwide users ranged from August 2016, September 2014, respectively, to August 2020. Data from the Polish population was collected from 10,679 readers and 92,627 sensors with 22.3 million glucose scans and 113 million automatically-recorded glucose readings, while the worldwide database included information from 981,876 readers and 11,179,229 sensors with 13.1 billion glucose readings. On average, the Polish users of isCGM performed substantially more scans/day (21.2±14.2 vs. 13.2±10.7), were characterized by considerably lower eHbA1c (7.0±1.2% vs. 7.5±1.5%), spent more TIR (64.2±17.3% vs. 58.1±20.3%) and less TAR (29.7±18.0% vs. 36.6±21.3%) (p&lt;0.0001 for all comparisons). Moreover, Polish users were more likely to achieve TIR&gt;70% (36.3% vs. 28.8%). Our results confirmed earlier findings that analyzed glucometrics improve as scan rate frequency increases; however, additional analyses showed that at the same scanning frequency, Polish users achieved lower eHbA1c, higher TIR, lower TAR, but higher TBR than the comparative group.
In summary, we report more scanning and better glycemic control in Polish isCGM users than worldwide. Due to the nature of this study, we are not able to explain the cause of this observation. It could be associated with demographic characteristics, such as a higher proportion of adult users, or more efficient diabetes education. Our data seems to suggest more frequent scanning than currently recommended.

Disclosure
J. Hohendorff: Advisory Panel; Self; Abbott, Roche Diabetes Care, Other Relationship; Self; Merck & Co., Inc., Polfa Tarchomin S. A. J. Gumprecht: Advisory Panel; Self; Abbott, Research Support; Self; Bayer AG, Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Bioton S. A., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S, Sanofi. M. Mysliwiec: None. D. Zozulinska-ziolkiewicz: None. M. Malecki: Advisory Panel; Self; Abbott Diabetes, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Mundipharma International, Novo Nordisk, Sanofi-Aventis, Servier Laboratories.
657-P: Potential Effect of a Novel Combination of GLP-1RA (efpeglenatide) and Long-Acting Glucagon Analog (HM15136) in Animal Models of Metabolic Disorders
Authors: LEE JONG SUK , KIM JUNG KUK , LEE SEON MYEONG , CHOI JAEHYUK , PARK EUNJIN , KIM DAEJIN , BAE SUNGMIN , LEE SANG HYUN , CHOI IN YOUNG 
Published: June 2021

In addition to glycemic control, GLP-1RA efficacy is established in obesity. However, more efforts are still required to close efficacy gap with bariatric surgery. Recent studies demonstrate the favorable effect of glucagon (GCG) receptor activation on energy expenditure and hepatic lipid metabolism. So, combination of GCG with GLP-1RA not only enhances body weight loss (BWL) barely achieved by current therapy, but also expands its therapeutic utility to various metabolic disorders. Previously, we confirmed the long-acting GCG properties of HM15136 from animal to human. In addition, GLP-1 class effect of efpeglenatide (Efpe), once-weekly GLP-1RA, was confirmed in clinical studies. Thus, to develop a novel combination therapy, we investigated potential effects of Efpe and HM15136 combination in animal models of metabolic disorders. In DIO mice, 4 weeks treatment of Efpe and HM15136 combination (COMBO) showed more BWL than Efpe mono treatment. Of note, greater BWL was also confirmed for COMBO treatment compared to acylated GLP-1/GIP co-agonist (-18.5, -55.9, -44.9% vs. vehicle for Efpe, COMBO, GLP-1/GIP). Similar results were observed when measuring fat mass (-19.5%, -83.8%, -77.2% vs. vehicle for Efpe, COMBO, GLP-1/GIP) and blood lipid profiles (total cholesterol: -41.8%, -82.0%, -63.2% vs. vehicle for Efpe, COMBO, GLP-1/GIP) in DIO mice. To further demonstrate benefits of this novel COMBO, additional study was performed in DIO/STZ rats, and COMBO treatment consistently showed more BWL than Efpe (-5.1, -12.1% vs. vehicle for Efpe, COMBO) along with numerically more HbA1c reduction (-1.0, -1.5% vs. vehicle for Efpe, COMBO). Therefore, HM15136 might be a novel COMBO partner for Efpe, providing enhanced BWL and favorable metabolic profiles. These results warrants further evaluation for therapeutic potential of this novel COMBO in various metabolic disorders including dyslipidemia and NASH.

Disclosure
J. Lee: Employee; Self; Hanmi Pharmaceutical. J. Kim: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. J. Choi: Employee; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. D. Kim: Employee; Self; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical.
742-P: Phase 1 Study of Safety, Tolerability, PK, and PD of Once-Weekly Basal Insulin Fc (BIF) in Japanese Patients with T2DM
Authors: OHWAKI KENJI , FURIHATA KENICHI , NASU RISA , OURA TOMONORI , IMORI MAKOTO 
Published: June 2021

BIF (LY3209590) is a novel, once weekly, long-acting IgG Fc-fusion protein that is being assessed for the treatment of diabetes mellitus. This phase 1, multiple-site, randomized, single-dose, dose-escalation study of BIF included 3 cohorts. Cohorts 1 and 2 each included 12 Japanese insulin-naïve patients with T2DM who were randomized double-blind to receive a single SC dose (dose 1 in cohort 1; dose 2 in cohort 2) of BIF (N=8) or placebo (N=4). Cohort 3 included 7 Japanese patients with T2DM previously treated with basal insulin, with or without a stable dose of up to 2 prespecified types of oral anti-hyperglycemic medications, who received a single SC dose of open-label BIF at dose 3. The primary objective was to investigate safety and tolerability. Secondary objectives included characterization of the PK and PD. ClinicalTrials.gov identifier: NCT03603704. Four patients (12.9%; 1 patient in each treatment group) reported a treatment-emergent adverse event; all were mild and none were related to study drug. Six patients (19.4%) reported hypoglycemic events (most events were with dose 3 and none were severe); each event was self-treatable and resulted in a prompt recovery. PK analyses showed BIF exposure after administration of each dose increased with dose, and tmax was observed by approximately day 4 at all 3 doses. The geometric mean t1/2 estimates ranged from 11 to 16 days across doses. All 3 doses decreased fasting glucose from baseline to day 15. Fasting glucose decreased from day 2 until approximately day 7 or 8 at all doses followed by a trend of fasting glucose returning to baseline. Compared with placebo, BIF at doses 1 and 2 significantly decreased (p&lt;0.1) fasting glucose levels from baseline at most time points between days 3 and 15. In Japanese patients with T2DM, single SC doses of BIF were well tolerated, and the PK and PD of BIF allows weekly dosing.

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

Funding
Eli Lilly and Company
762-P: Use of Oral Hypoglycemic Agents in Type 1 DM
Authors: ROMO KARINA G. , WEST WILLIAM A. , UWAIFO GABRIEL I. 
Published: June 2021

Obesity prevalence in T1DM is increasing. While T1DM is typically treated exclusively with insulin, the changing obesity trends and T1DM heterogeneity has raised interest in use of various oral hypoglycemic agents (OHA) as adjunctive therapy. The extent and impact of OHA “off label” use in “real world” settings is not well studied. We report on the extent, distribution, glycemic and cardiometabolic impact of OHA use in a T1DM cohort. Retrospective chart review of 300 patients with health record coded T1DM seen between January 2015 and January 2018 was done. OHA use, comorbidities, demographics, vital signs, and cardiometabolic risk surrogates were extracted for analyses.. The chart review showed actual DM subtypes were :163 (54%) T1DM, 43 (14.3%) Latent Autoimmune Diabetes of Aging (LADA), 1 (0.3%) maturity-onset diabetes of the young, 2 (0.7%) type 1.5 (essentially LADA), 8 (2.7%) type 1+2 (T1DM with obesity and insulin resistance), 11 (3.7%) deceased, and 71 (23.7%) T2DM that had been miscoded as T1DM. All subsequent analyses included T1DM, LADA, type 1.5, and type 1+2 in the verified T1DM cohort. 16% of the T1DM cohort were on at least one OHA and most common were sulphonylureas (16%), DPP-4 blockers (15.3%), SGLT-2 blockers (11%) and metformin (9.2%). OHA use in T1DM was not associated with any significant change in weight, BMI nor blood pressure. There was however a statistically significant decline in total cholesterol, LDL and HBA1c but not fasting triglycerides. No significant differences were found in hypoglycemia related admissions or DKA admissions with OHA use including among SGLT-2 users. Off label use of OHAs is quite prevalent in the studied population of patients with T1DM (16%) and their use was associated with improvements in HBA1c and aspects of lipid metabolism despite no significant changes in weight, BMI or blood pressure. OHAs may have utility as adjunctive therapy and require more structured study to enable development of therapeutic algorithms for their use in T1DM therapeutics.

Disclosure
K. G. Romo: None. W. A. West: None. G. I. Uwaifo: None.
802-P: Dapagliflozin Improves Glycolytic Reserve in Peripheral Blood Mononuclear Cells in Patients with Type 1 Diabetes
Authors: MELO JOANA , LAURSEN JENS CHRISTIAN , HEINRICH NIELS S. , RASMUSSEN IDA B. , HANSEN CHRISTIAN S. , FRIMODT-MOELLER MARIE , ROSSING PETER , STØRLING JOACHIM 
Published: June 2021

Sodium-glucose cotransporter-2 (SGLT2) inhibition is emerging as a beneficial adjunctive therapy in type 1 diabetes (T1D). It is hypothesized that SGLT2 inhibition relieves hypoxia in the kidneys. As mitochondrial dysfunction might contribute to kidney hypoxia, SGLT2 inhibition could ameliorate hypoxia via restored mitochondrial respiration. Changes in metabolic processes in peripheral blood mononuclear cells (PBMCs) are associated with various diseases including diabetes. PBMCs are an easily accessible reporter cell population to test changes in cellular metabolism caused by changes in blood glucose. The aim of this study was to investigate the effects of a single dose of 50 mg dapagliflozin compared to placebo on PBMCs’ bioenergetics in individuals with T1D in a double blinded randomized crossover study with a two-week washout period. With Seahorse extracellular flux technology, we analysed the efficiency of mitochondrial oxidative phosphorylation and glycolysis in PBMCs obtained from a fresh blood sample of each study participant before and after intervention. Fifteen individuals (33% females) with mean (±SD) age 58 (±14) years and Hba1c 8.0 (±0.6) % were included. Dapagliflozin did not influence PBMC mitochondrial oxidative phosphorylation. However, dapagliflozin significantly improved PBMC glycolytic reserve by 35% (mean ±SE, 3.5 ±0.3 e-6 ECAR/cell number) compared to baseline (2.6 ±0.5 e-6 ECAR/cell number). Our results suggest that dapagliflozin enhances PBMCs’ flexibility to use glycolysis as an energy supply pathway in individuals with T1D. This study advances our mechanistic understanding of the subtle changes in systemic metabolism and the beneficial effects at the cellular level of SGLT2 inhibition in patients with T1D.

Disclosure
J. Melo: None. J. Laursen: None. N. S. Heinrich: Stock/Shareholder; Self; Akebia Therapeutics, Inc., Novo Nordisk A/S. I. B. Rasmussen: None. C. S. Hansen: None. M. Frimodt-moeller: None. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. J. Størling: None.
808-P: Economic Benefits of Initiating Empagliflozin vs. GLP-1 Receptor Agonists among Patients with Type 2 Diabetes
Authors: PIMPLE PRATIK , RAJU ADITYA , FARRELLY EILEEN , SHETTY SHARASH 
Published: June 2021

Background: SGLT-2 inhibitors and GLP-1 receptor agonists (GLP-1RAs) have proven clinical benefit profiles, and the ADA recommends both as treatment options for T2D patients uncontrolled on metformin. There is limited research on whether these clinical benefits translate into differential cost savings. This study sought to assess the all-cause (AC) healthcare costs associated with initiating empagliflozin (EMPA) vs. GLP-1RAs among patients with T2D.
Methods: A commercial US claims database was used to identify patients with T2D who newly initiated EMPA or GLP-1 RA from 08/2014-09/2018. Study cohorts (EMPA users and GLP-1RA users) were matched using propensity scores (PSs) (1:1 ratio, caliper: ± 0.05) based on baseline demographic and clinical variables. AC costs were computed on a per patient per month (PPPM) basis during a variable follow-up period of up to 12 months and compared across study cohorts using generalized linear models. A subanalysis comparing AC costs among patients who initiated second-line treatment with EMPA or GLP-1RA after metformin monotherapy was also conducted.
Results: PS matching resulted in a sample of 43,588 patients (21,794 patients in each group) whose mean age was 54 years and 63% were male. The total AC PPPM costs were significantly lower for EMPA vs. GLP-1RA users ($1,450 vs. $1,723; Δ = $273; P&lt;0.001), with both pharmacy (Δ = $195; P&lt;0.001) and medical (Δ = $78; P=0.006) costs being significantly lower. Similar results were observed in the subanalysis where initiating EMPA after metformin monotherapy was associated with lower AC PPPM costs compared to GLP-1RA users (Δ = $271; P&lt;0.001).
Conclusion: Among patients with T2D, initiating EMPA vs. GLP-1RA was associated with lower AC healthcare costs, where the drivers were both lower medical and pharmacy costs. These findings can inform treatment selection processes that are aimed to optimize T2D management, especially from an economic perspective.

Disclosure
P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Raju: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited, Employee; Self; Xcenda LLC, Stock/Shareholder; Self; Teva Pharmaceutical Industries Ltd. E. Farrelly: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited, Employee; Self; Xcenda LLC. S. Shetty: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding
Boehringer Ingelheim