bluuebunny/crossref_metadata_2025_split huggingface dataset:
306-OR: Modified Approach for Improved Islet Allotransplantation into Prevascularized Sernova Cell Pouch Device: Preliminary Results of the Phase I/II Clinical Trial at University of Chicago
Authors: BACHUL PIOTR J. , PEREZ-GUTIERREZ ANGELICA , JUENGEL BRADEN , GOLAB KAROLINA , BASTO LINDSAY , PEREA LAURENCIA , WANG LINGJIA , TIBUDAN MARTIN , THOMAS CELESTE , PHILIPSON LOUIS H. , BARTH ROLF , FUNG JOHN , WITKOWSKI PIOTR 
Published: May 2022

Introduction: After the pilot study demonstrated safety of the Sernova Cell Pouch (SCP) , we modified islet transplantation (ITx) conditions for improved engraftment in the SCP.
Methods: SCPs were implanted in the abdominal anterior rectus sheath of 7 patients with T1DM and problematic hypoglycemia. Immunosuppression was initiated 1 month after SCP implantation and a marginal dose ITx of highly purified islets 1 month later. A second ITx was scheduled 6 to 12 months later. Sentinel SCPs are explanted for histopathology 3 months after ITx. Graft function is monitored by blood glucose (BG) , C-peptide and insulin usage.
Results: Seven patients underwent 27 study-related surgeries with wound infection in 2 (7.4%) patients after SCP implantation. One patient discontinued following device excision and the second patient’s infection resolved. SCPs are well tolerated with implant durations exceeding 35 months. Three patients received two ITx into SCPs, resulting in new, measurable islet function documented by detectable levels of stimulated C-peptide. A supplemental, single intraportal ITx was sufficient for the first two patients to achieve ongoing insulin independence and freedom from severe hypoglycemic events for over 22 and 4 months with HbA1c 5.4 and 5.5%, respectively. The third patient discontinued insulin support 2 months after a single supplemental intraportal ITx and presented normal blood glucose control during MMTT on post-transplant day 75 with fasting and peak values of 97 and 142mg/ml, respectively, serum C-peptide of 1. and 3.39 ng/ml and HbA1c of 5.8%. The other three patients on study are progressing as planned. All have received SCP implants and at least one ITx.
Conclusion: ITx with SCP demonstrates long-term safety and efficacy in an early subset of trial patients. Ongoing results for transplanted SCPs have led to procedural adjustments to further optimize clinical outcomes.

Disclosure
P.J.Bachul: None. L.H.Philipson: Advisory Panel; Nevro Corp., Research Support; Dompé, Novo Nordisk, provention BIo. R.Barth: None. J.Fung: n/a. P.Witkowski: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated. A.Perez-gutierrez: None. B.Juengel: None. K.Golab: None. L.Basto: None. L.Perea: None. L.Wang: None. M.Tibudan: None. C.Thomas: None.
328-OR: Evaluation of Mobile Health Technology–Based Diabetes Education System for Self-Management of Patients with Type 2 Diabetes Mellitus
Authors: SI CHEN , LU JINGYI , BAO YUQIAN , ZHOU JIAN , JIA WEIPING 
Published: May 2022

Ongoing research has established that mobile health applications (apps) are feasible tools for improving self-management of diabetes and to maintain glycemic control. This single-arm, multi-center, observational study evaluated the effectiveness of an app-based diabetes education program in improving HbA1c among patients with type 2 diabetes mellitus (T2DM) treated with premixed insulin for 12 weeks. A total of 9426 patients were included. Primary endpoint was the change in HbA1c from baseline to week 12. Secondary endpoints included the association of HbA1c reduction with number of diabetes education courses completed and learning mode, and the association of SMBG frequency with diabetes education courses. According to the number of diabetes education courses completed, the patients were divided into 3 groups: 0-4 courses, 5-29 courses, and ≥30 courses. After 12 weeks of engagement in app, there was a decrease in HbA1c levels (9.84 ± 1.47 % vs. 7.36 ± 1.15 %) with 36% of patients achieving HbA1c target at week 12. The HbA1c control rate was the highest among patients completing ≥30 courses (49%; mean change: -2.9%) , followed by those who completed 5-29 courses (38%; -2.7%) and 0-4 courses (35%; -2.4%) (P&lt;0.0001) . Besides, the frequency of SMBG testing increased with the ascending number of courses completed (≥30 courses: 7.4 times/week; 5-29 courses: 3.5 times/week; 0-4 courses: 1.2 times/week; P&lt;0.0001) . HbA1c reduction (-2.7% vs. -2.4%; P&lt;0.0001) and the proportion of patients with HbA1c &lt;7% (42% vs. 35%; P&lt;0.0001) were significantly lower in patients who preferred audio-visual learning over visual learning for diabetes course engagement. To summarize, participants who completed more diabetes education courses had better HbA1c reduction over 12 weeks and better self-management of blood glucose with the app.

Disclosure
C.Si: None. J.Lu: None. Y.Bao: None. J.Zhou: n/a. W.Jia: None.
334-OR: Pemvidutide (ALT-801) , a Balanced (1:1) GLP-1/Glucagon Dual Receptor Agonist, Induces Rapid and Marked Weight Loss without the Need for Dose Titration in People with Overweight/Obesity
Authors: KLEIN SAMUEL , NESTOR JOHN J. , HARRIS M. SCOTT , SUYUNDIKOV ANVAR , CASPER ROB , STEELE STACI M. , PAYNE JACQUES D. , KRISHNAN VYJAYANTHI , ROBERTS M. SCOT , BROWNE SARAH K. 
Published: May 2022

Background: Weight loss is the cornerstone of therapy for people with overweight/obesity. Pemvidutide is a dual GLP-1/glucagon receptor agonist that provides GLP-1/glucagon agonism in a balanced (1:1) ratio, which is hypothesized to enhance weight loss and minimize gastrointestinal intolerance.
Methods: 34 subjects with overweight/obesity (BMI 25.0-40.0 kg/m2) without diabetes were randomized in double-blind manner to pemvidutide (1.2, 1.8 or 2.4 mg) or placebo subcutaneously weekly for 12 weeks without dose titration or lifestyle therapy. Study endpoints included safety/tolerability, weight loss and cardiometabolic outcomes.
Results: At 12 weeks, significant weight loss was achieved with 1.8 mg (10.3%) and 2.4 mg (9.0%) of pemvidutide, and significant improvements or trends in cardiometabolic risk factors were observed at all pemvidutide doses (Table 1) . No increases in heart rate, fasting glucose or HbA1c were observed in any group. Mild, transient nausea was the most frequent adverse event (AE) ; no severe/serious AEs or AE-related study discontinuations were reported.
Conclusion: Pemvidutide induces robust weight loss and improves cardiometabolic risk factors without dose titration. These data support the development of pemvidutide as a promising treatment for obesity and its comorbidities.

Disclosure
S.Klein: Advisory Panel; Altimmune, Consultant; Janssen Research & Development, LLC, ProSciento, Research Support; Janssen Research & Development, LLC. S.K.Browne: Employee; Altimmune. J.J.Nestor: Consultant; Altimmune, Employee; EuMederis Pharmaceutials, Inc., Mederis Diabetes, LLC, Spitfire Pharma, Inc. M.Harris: Employee; Altimmune. A.Suyundikov: Employee; Altimmune. R.Casper: Employee; Altimmune. S.M.Steele: Employee; Altimmune. J.D.Payne: None. V.Krishnan: Employee; Altimmune. M.Roberts: Employee; Altimmune.

Funding
Altimmune, Inc.
337-OR: Tirzepatide Improved Markers of Islet-Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared with Semaglutide in People with Type 2 Diabetes
Authors: BROWN KATELYN , LANDO LAURA FERNANDEZ , BERGMAN BRANDON , THOMAS MELISSA K. , LIU BING , LEE CLARE 
Published: May 2022

Tirzepatide (TZP) achieved significantly greater HbA1c and weight reductions with all doses (5, and 15 mg) vs. semaglutide 1 mg (SEMA) in a Phase 3 trial of 1879 people with type 2 diabetes (T2D) on background metformin (mean age 56.6 years; T2D duration 8.6 years; baseline HbA1c 8.3% [67 mmol/mol]; BMI 34.2 kg/m2) (SURPASS-2) . Changes in fasting markers of islet cell function and insulin sensitivity were assessed by mixed model repeated measures in the modified intent-to-treat population. At 40 weeks, all TZP doses improved HOMA2-B, calculated with C-peptide, as indicated by a significant increase by 97-120% on average with TZP, compared to 84% with SEMA. Fasting glucagon levels, adjusted for fasting serum glucose, significantly decreased by 53-55% on average with TZP and 15 mg doses compared with SEMA (48%) . All TZP doses improved insulin sensitivity as reflected by a significant decrease by 16-24% on average of HOMA2-IR, calculated with insulin, compared to a decrease by 5% with SEMA. Fasting insulin levels were also significantly reduced by 9-21% on average with all TZP doses compared to an increase of 0.6% with SEMA. Dual GIP/GLP-1 receptor agonist TZP significantly improved markers of islet cell function and insulin sensitivity compared to selective GLP-1 RA SEMA in people with T2D.

Disclosure
K. Brown: Employee; Eli Lilly and Company. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.K. Thomas: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Liu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
355-OR: WATCH-DM Identifies Diabetic Cardiomyopathy: A Multicohort Analysis
Authors: SEGAR MATTHEW W. , PATEL KERSHAW , VADUGANATHAN MUTHIAH , CHANDRA ALVIN , WILLETT DUWAYNE L. , PANDEY AMBARISH 
Published: May 2022

Introduction: Diabetic cardiomyopathy (DbCM) , a transitional phenotype that may precede overt heart failure (HF) onset, is characterized by abnormalities in cardiac structure or function in DM in the absence of cardiovascular disease (CVD) or major risk factors. Whether WATCH-DM, a validated risk score to identify incident heart failure (HF) among individuals with DM, can identify DbCM is unknown.
Methods: Adults without known prevalent CAD or overt HF were pooled from 2 community-based cohort studies (ARIC and CHS) . Presence of DbCM in patients with DM was defined using different definitions (Figure) . Adjusted logistic regression and restricted spline models were used to evaluate the association of WATCH-DM and the individual components of DbCM.
Results: Among 2,241 individuals with DM, the prevalence of DbCM was 9.8% and 62.8% applying the most and least restrictive definitions, respectively. For every 1-unit increase, the WATCH-DM score was associated with higher risk of LV hypertrophy and diastolic dysfunction (odds ratio [95% CI] = 1.20 [1.15-1.27] and 1.[1.05-1.13], respectively) , but not LA enlargement (Figure A) . Across definitions, higher WATCH-DM scores were associated with a higher risk of DbCM (Figure B) .
Conclusions: The WATCH-DM risk score is associated with higher prevalence of DbCM and may be a useful tool in screening for DbCM.

Disclosure
M.W.Segar: None. K.Patel: None. M.Vaduganathan: Advisory Panel; American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, Other Relationship; Novartis and Galmed , Research Support; Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Sanofi, Speaker's Bureau; Novartis and Roche Diagnostics. A.Chandra: None. D.L.Willett: None. A.Pandey: Advisory Panel; Lilly, Consultant; Tricog, Research Support; Applied Therapeutics, Gilead Sciences, Inc.
36-OR: Bromocriptine Quick Release (BCQR) Improves Vascular Health in Youth with Type 1 Diabetes Even if Normal Weight
Authors: SCHÄFER MICHAL , BROWNE LORNA , TRUONG UYEN , BJORNSTAD PETTER , SNELL-BERGEON JANET K. , BAUMGARTNER AMY , HUNTER KENDALL S. , REUSCH JANE , BARKER ALEX J. , SCHAUER IRENE E. , NADEAU KRISTEN J. 
Published: May 2022

Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth.
Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment.
Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p&lt;0.001) and diastolic BP (∆ = -2 mmHg, p=0.039) . BCQR reduced ascending aortic (AA) PWV (∆ = -0.4 m/s, p=0.005) , and increased RAC (∆ = -2.6%, p=0.022) and distensibility (∆ = 0.%/mmHg, p=0.010) . In the thoraco-abdominal aorta, BCQR decreased PWV (∆ = -0.2 m/s, p=0.013) and increased distensibility (∆ = 0.%/mmHg, p=0.032) . Of interest, in the normal-weight participants, BCQR improved systolic BP (∆ = -5 [95.0%CI: -7, -1] mmHg, p= 0.009) , AA PWV (∆ = -0.4 [95.0%CI: -0.7, 0] m/s, p= 0.030) and BrachD (∆ = 0.56 %/mmHg, p=0.023) , and tended to improve AA distensibility (∆ = 0.[95.0%CI: -0.01, 0.19] %/mmHg, p= 0.084) .
Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies.

Disclosure
M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None.

Funding
JDRF BROM QR THERP3-SRA-2015-125-M-R
374-P: Identifying the Role and Mechanism by Which GDF15 Enhances the Counterregulatory Response to Hypoglycemia
Authors: LI ZONGYU , ZHANG XINYI , ZHU WANLING , XU QIAN , YU CHUYUE , LIMA BRUNA G. COSTA , LI XIRUO , ISRANI-WINGER KAVITA , NASIRI ALI , ZHANG CUILING , CHANG RUI , HWANG JANICE J. , WANG ANDREW , PERRY RACHEL J. 
Published: May 2022

Severe hypoglycemia is the leading acute mortality risk in patients with diabetes. The counterregulatory gluconeogenic and glycogenolytic response to hypoglycemia is the primary adaptive mechanism to enable survival. To better understand the hormonal response that orchestrates hypoglycemia counterregulation, we employed the insulin tolerance test (ITT) and hyperinsulinemic-hypoglycemic clamp to mimic the two common settings in which hypoglycemia can occur in patients: postprandial insulin overdose and elevated basal insulin infusion, respectively. We found that Growth Differentiation Factor 15 (GDF15) can be induced (33.5±2.1 vs. 172.4±29.2 pg/ml, P&lt;0.in ITT and 46.2±11.6 vs. 2865±547.3 pg/ml, P&lt;0.0in the clamp) . GDF15 mRNA and protein are upregulated in kidney, and the GDF15 tdTomato reporter mouse demonstrates the expression of GDF15 in the S3 segment of the proximal tubule. GDF15 increases hepatic gluconeogenesis (26.1±2.2 vs. 33.5±1.6 mg/kg/min, P&lt;0.05) by increasing intrahepatic lipolysis in a beta-adrenergic receptor-2 (Adrb2) -dependent manner. To investigate the role of GDF15 counterregulation in diabetes, we utilized a streptozotocin (STZ) -induced type 1 diabetes (T1D) model. Mice with T1D exhibit impaired GDF15 production in an ITT. Additionally, we found that recurrent hypoglycemia impairs endogenous glucose production during hypoglycemia in mice (27.5±4 vs. 10.5±1.3 mg/kg/min, P&lt;0.01) , which may result from lower GDF15 production (1372±248.2 vs. 648.5±71.3 pg/ml, P&lt;0.05) . In humans, hypoglycemic clamps in healthy volunteers can induce GDF15 production (p=0.01) , although this induction was absent in patients with T1D. Conclusion: These data show the kidney can produce GDF15 in response to hypoglycemia, thereby increasing hepatic gluconeogenesis to enable survival. However, T1D patients are unable to initiate a functional GDF15 signaling pathway resulting in an impaired glucose counterregulatory response to hypoglycemia.

Disclosure
Z.Li: None. C.Zhang: None. R.Chang: None. J.J.Hwang: None. A.Wang: Research Support; NGM Biopharmaceuticals. R.J.Perry: None. X.Zhang: None. W.Zhu: None. Q.Xu: None. C.Yu: None. B.G.Costa lima: None. X.Li: None. K.Israni-winger: None. A.Nasiri: None.

Funding
National Institutes of Health (P30 DK045735) National Institutes of Health (R37 CA258271-01A1)
375-P: Indirect Treatment Comparison (ITC) of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia: Baqsimi, Gvoke, and Zegalogue
Authors: GIMENEZ MARGA , KHUNTI KAMLESH , SYRING KRISTEN , BAKER LEVENIA A. , CHENJI SURESH , THRELKELD REBECCA J. , YAN YU , MATSUHISA MUNEHIDE 
Published: May 2022

Objective: To evaluate and compare the efficacy and safety of 3 ready-to-use glucagon treatments for severe hypoglycemia in adults and children with diabetes: Baqsimi (nasal glucagon) , Gvoke (glucagon injection) , and Zegalogue (dasiglucagon injection) .
Methods: A systematic literature review was conducted to identify randomized clinical trials assessing the efficacy and safety of ready-to-use glucagon vs. reconstituted injectable glucagon. Bayesian fixed-effect network meta-analysis was used to perform the ITC of Gvoke and Zegalogue vs. Baqsimi. Endpoints included the proportion of participants achieving treatment success, maximum blood glucose, and treatment-emergent adverse events. Mean time to treatment success and to maximum blood glucose were also analyzed for Gvoke vs. Baqsimi, but not for Zegalogue due to reporting differences (mean vs. median) .
Results and Conclusion: Ten trials were included in the ITC, including 4 for Baqsimi, 3 for Gvoke, and 3 for Zegalogue. Baqsimi had comparable efficacy with Gvoke and with Zegalogue (Table) , and all 3 treatments achieved high treatment success (&gt;98%) in adults and children with diabetes. In adults, results from the combined T1D and T2D analysis were consistent with the T1D analysis, except a statistically significant faster time achieving treatment success observed for Baqsimi vs. Gvoke in the combined analysis.

Disclosure
M. Gimenez: Advisory Panel; Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. K. Khunti: Consultant; Abbott, Amgen Inc., AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Lilly, Merck Sharp & Dohme Corp., Napp Pharmaceuticals Limited, Novartis AG, Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Servier Laboratories. Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. K. Syring: Employee; Eli Lilly and Company. L.A. Baker: None. R.J. Threlkeld: Employee; Lilly Diabetes. Y. Yan: Employee; Eli Lilly and Company. M. Matsuhisa: Research Support; Nissui, Sysmex Corp. Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding
Funded by Eli Lilly and Company.
407-P: Skin Autofluorescence Is Associated with Tubular Injury Represented by Urinary Excretion of Liver-Type Fatty Acid–Binding Protein in People with Diabetes
Authors: YAMAGAMI HIROKI , YASUI SAYA , HOSOKI MINAE , HORI TAIKI , HARA TOMOYO , MITSUI YUKARI , KURAHASHI KIYOE , NAKAMURA SHINGEN , OTODA TOSHIKI , YUASA TOMOYUKI , YOSHIDA SUMIKO , KURODA AKIO , MATSUHISA MUNEHIDE , ENDO ITSURO , AIHARA KEN-ICHI , ABE MASAHIRO 
Published: May 2022

Background: Advanced glycation end product (AGE) accumulation is thought to be an independent predictor for cardiovascular disease in people with diabetes and renal failure. Since it has remained unclear whether AGE has a clinical impact on diabetic kidney disease (DKD) , the aim of this study was to determine the association between AGE accumulation, measured as skin autofluorescence (AF) , and the progression of DKD.
Methods: Skin AF was measured by AGE reader® and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP) , were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 300 Japanese people with diabetes (173 males and 127 females, mean age, 67.8 ± 10.7 years) . The relationships between skin AF and those urine biomarkers of DKD were statistically evaluated.
Results: Simple regression analysis showed that skin AF was associated with uACR (p&lt;0.05) , log-transformed uACR (p&lt;0.01) and uL-FABPCR (p&lt;0.001) . On the other hand, multivariate regression analysis including clinical confounding factors showed that skin AF independently contributed to the increment of uL-FABPCR (P &lt;0.05) but not to that of uACR (P=0.399) or log-transformed uACR (P=0.315) .
Conclusion: Skin AF was associated with urinary L-FABP but not with albuminuria in people with diabetes. The results suggest that skin AF can serve as a novel predictive factor for the development of diabetic tubular injury.

Disclosure
H.Yamagami: None. T.Yuasa: None. S.Yoshida: None. A.Kuroda: None. M.Matsuhisa: Research Support; Nissui , Sysmex Corp., Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. I.Endo: None. K.Aihara: None. M.Abe: None. S.Yasui: None. M.Hosoki: None. T.Hori: None. T.Hara: None. Y.Mitsui: None. K.Kurahashi: None. S.Nakamura: None. T.Otoda: None.