bluuebunny/crossref_metadata_2025_split huggingface dataset:
1869-LB: Efficacy and Safety of iGlarLixi vs. IDegAsp in Chinese People with Type 2 Diabetes (T2D) Suboptimally Controlled with Oral Antidiabetic Drug(s) (OAD)—The SoliD Randomized Controlled Trial
Authors: LIU MING , GU WEIJUN , CHEN LI , LI YANBING , KUANG HONGYU , DU JIANLING , ALVAREZ AGUSTINA , LAUAND FELIPE , SOUHAMI ELISABETH , ZHANG JIEWEN , XU WEIYA , DU QIN , MU YIMING 
Published: June 2024

Introduction and Objective: SoliD (NCT05413369) compared the efficacy and safety of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL + lixisenatide, vs insulin degludec + insulin aspart (IDegAsp) in Chinese people with T2D suboptimally controlled with OAD(s).
Methods: In this 24-week, multicenter, open-label, Phase 3 study, insulin-naïve people with HbA1c 7-11% were randomized 1:1 to once-daily iGlarLixi (n=291) or IDegAsp (n=291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was noninferiority in HbA1c change from baseline to Week 24. Secondary endpoints included superiority for HbA1c change, body weight (BW) change, proportion of people with HbA1c &lt;7.0% at Week 24, composite endpoints, and hypoglycemia rates.
Results: At Week 24, iGlarLixi demonstrated noninferiority, with least squares (LS) mean difference −0.20 (95% confidence interval [CI]: −0.33, −0.07; p&lt;0.001) and superiority (97.5% CI: −0.35, −0.05; p=0.003) vs IDegAsp in HbA1c reduction. iGlarLixi resulted in a decrease in BW and IDegAsp resulted in an increase in BW from baseline to Week 24, with a LS mean difference of −1.49 kg (97.5% CI: −2.32, −0.66; p&lt;0.001). Other secondary endpoints at Week 24 also favored iGlarLixi vs IDegAsp, respectively (p&lt;0.001 for all): HbA1c &lt;7.0% (72.5% vs 59.8%); HbA1c &lt;7.0% + no BW gain (40.5% vs 21.3%); HbA1c &lt;7.0% + no BW gain + no hypoglycemic events (26.5% vs 13.4%). Event rates (per-person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycemia were lower for iGlarLixi (1.90) vs IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycemia or unexpected safety findings were reported.
Conclusion: In Chinese people with T2D, suboptimally controlled on OAD(s), iGlarLixi achieved superior improvements in glycemic control, prevention of BW gain and a lower hypoglycemic event rate vs IDegAsp.

Disclosure
M. Liu: None. W. Gu: None. L. Chen: None. Y. Li: Consultant; Sanofi, Novo Nordisk, AstraZeneca. H. Kuang: None. J. Du: None. A. Alvarez: Employee; Sanofi. Stock/Shareholder; Sanofi. F. Lauand: Employee; Sanofi. Stock/Shareholder; Sanofi. E. Souhami: Employee; Sanofi. Stock/Shareholder; Sanofi. J. Zhang: Employee; Sanofi. W. Xu: Employee; Sanofi. Q. Du: None. Y. Mu: Speaker's Bureau; Novo Nordisk, Sanofi, Lilly Diabetes.

Funding
Sanofi
1898-LB: Interim Analysis of a Study Investigating User Satisfaction and Metabolic Outcome of PwT1D Using an Innovative Micropump
Authors: DAIN ALEJANDRO , SCHEIBNER KATHARINA , MOCERI SANDRA , DAGENBACH NICOLE , VULCANO CRISTINA , VOGT GERHARD , BEST JULIA , ETTER TOBIAS J. 
Published: June 2024

Aims: People with type 1 diabetes (PwT1D) use either multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), but CSII adoption is limited. Therefore, this study examines how the transition from MDI to CSII, utilizing an innovative modular micropump system, affects treatment satisfaction and metabolic outcomes.
Methods: 50 CSII-naive Argentinian PwT1D were enrolled in a multicenter, prospective, single-armed study for the Accu-Chek® Solo micropump system (ACS). Outcome: Change in diabetes treatment satisfaction (assessed by the Diabetes Technology Questionnare (DTQ) and HbA1c after 13 weeks as well as 1 and 2 years. Linear mixed models were utilized for analyses, with respective baseline scores as fixed effects and site as random effect.
Results: The change score of the “Impact and satisfaction” part of the DTQ was 113.37 ± 16.74 (mean ± SD, p &lt; 0.0001) after 13 weeks, 111.42 ± 14.42 (p &lt; 0.0001) after 1 year and 107.78 ± 16.14 after 2 years (p = 0.0005) (90 = non-change score). The following mean DTQ change scores were measured after 13 weeks / 1 / 2 years: 3.81 ± 0.61 / 3.79 ± 0.52 / 3.73 ± 0.63 for “diabetes distress and burden”, 3.96 ± 0.68 / 3.98 ± 0.60 / 3.81 ± 0.79 for “hypoglycemia fear, worry and behavior”, 3.56 ± 0.71 / 3.53 ± 0.52 / 3.43 ± 0.67 for “device acceptance and satisfaction” (1 = much worse, 5 = much better). The mean HbA1c decreased from 8.20 % ± 1.34 to 7.93 % ± 1.19 (-0.28 %pt, p = 0.0375) after 13 weeks, 7.87 % ± 1.26 (-0.37 %pt, p = 0.0467) after 1 year and 7.95 % ± 1.32 (-0.28 %pt, p = 0.1716) after 2 years. Two events of severe hypoglycemia and one diabetic ketoacidosis (DKA) were reported during 32248 device days.
Conclusion: Transitioning from MDI to CSII with ACS resulted in a significant enhancement of participants' treatment satisfaction and HbA1c levels after 13 weeks and 1 year, and an improvement was sustained for up to year 2. This implies that using ACS diminishes the disease burden for people with T1D.

Disclosure
A. Dain: Research Support; Roche Diabetes Care. K. Scheibner: None. S. Moceri: Employee; Roche Diabetes Care. N. Dagenbach: Employee; Roche Diabetes Care. C. Vulcano: Employee; Roche Diabetes Care. G. Vogt: Employee; Roche Diabetes Care. J. Best: Employee; Roche Diabetes Care. T.J. Etter: None.
1905-LB: Eighteen-Month Follow-up Comparison of Simplified Meal Announcement vs. Precise Carbohydrate Counting in Adolescents with Type 1 Diabetes Using the MiniMed 780G Advanced Hybrid Closed-Loop System
Authors: PETROVSKI GORAN , CAMPBELL JUDITH , HUSSAIN KHALID , DIABETES GROUP SIDRA 
Published: June 2024

Aim: To compare glycaemic control in adolescents with Type 1 Diabetes (T1D) on Minimed 780G system with simplified meal announcement (fix) versus precise carbohydrate counting (flex) over an extended period of 18 months.
Methods: Adolescents with T1D were randomly distributed in a 1:1 ratio to utilize the MiniMed 780G system in conjunction with either the “flex” or “fix” meal announcement methods. Participants were followed for 18 months with data analysis at 3, 6, 12 and 18 months. The primary endpoint was the difference in time-in-range (TIR), and secondary endpoints included glycated hemoglobin (HbA1c) and other glucose and insulin metrics.
Results: At 18 months, TIR (70-180 mg/dL) was significantly higher in the flex versus fix group (80.9% versus 73.2%, respectively; p=0.001). There was no significant difference in HbA1c between the fix (6.9±0.6%) and flex groups (6.6±0.7%) at 18 months (p=0162). Glucose target of 100mg/dl, active insulin time of 2 hours and rule of 360 for carb ratio were used in &gt;90% of participants in both groups.
Conclusion: Using the MiniMed 780G system with a simplified meal announcement, adolescents can achieve and maintain the international targets of glycaemic control over an extended period (18 months); however, carbohydrate counting resulted in superior TIR.

Disclosure
G. Petrovski: None. J. Campbell: None. K. Hussain: None.
1926-LB: Use of Continuous Glucose Monitoring and Health Care Resource Utilization in Patients with Diabetes Treated with Sulfonylureas/Meglitinides
Authors: GALINDO RODOLFO J. , SREE BURUGAPALLI BHAVYA , BRANDNER LAURA , BINDAL ANILA 
Published: June 2024

Use of CGM has been associated with decreased risk for acute diabetes events (ADE) in patients treated with insulin therapy. In this study, we investigated the relationship of continuous glucose monitoring (CGM) use and ADE, all-cause hospitalizations (ACH), and emergency department (ED) visits among people with type 2 diabetes (T2D), treated with sulfonylurea (SU) or meglitinide therapy in the United States. This retrospective cohort study searched Inovalon Insights claims data for individuals with T2D, treated with SU/meglitinide, excluding insulin or GLP-1 RA users, and using FreeStyle Libre (FSL) between 01/2017 and 09/2023. Subgroup analysis was performed among participants &lt;65 and ≥65 years old. Two subgroups were analyzed: &lt;65 group: N = 2,976, mean age 54 ± 9 years, 41% female; ≥65 group: N = 1,895, mean age 73 ± 6 years, 43% female. For both subgroups, ADE, acute hyperglycemic events, ACH, and ED visit rates were significantly lower during CGM use period, compared to pre-CGM use (Table 1). Compared to pre-CGM use, patients on CGM with type 2 diabetes treated with SU/meglitinides had lower healthcare utilization. Further research should assess the financial and patient impact of these event reductions.

Disclosure
R.J. Galindo: Consultant; Abbott. Other Relationship; Dexcom, Inc. Consultant; Bayer Inc. Other Relationship; Novo Nordisk, Eli Lilly and Company. Consultant; Boehringer-Ingelheim, AstraZeneca. B. Burugapalli: Other Relationship; Riya Soft Solutions Inc. L. Brandner: Employee; Abbott. A. Bindal: Employee; Abbott.
2027-LB: Optimal Measures of Insulin-Regulated Lipolysis in Humans
Authors: SONG YILIN , LYTLE KELLI , JENSEN MICHAEL D. 
Published: June 2024

Introduction & Objective: The euglycemic, hyperinsulinemic clamp is considered the best approach to assess insulin action. We measured free fatty acid (FFA) release rates as a function of insulin concentrations. This data was analyzed to identify the optimal insulin infusion rate(s) to measure adipose tissue insulin resistance.
Methods: Twenty-seven volunteers, age 18 - 50, underwent two-step insulin clamp studies; 5 patients undergoing bariatric surgery and 22 enrolled in a weight loss lifestyle intervention program. The baseline BMI for the bariatric surgery and lifestyle studies were 30 - 38 kg/m2 and 40 - 50 kg/m2, respectively. Palmitate kinetics were measured with intravenous infusion of [U-13C]palmitate; the low and high dose insulin infusion rates for obese volunteers were 0.25 and 0.5 mU•kg-1•min-1. Each dose was administered for 2.5 h and plasma glucose concentrations were maintained at 90 - 95 mg/dL using with intravenous dextrose. We used the insulin concentration resulting in 50% suppression from baseline FFA-palmitate release (IC50) as the measure of adipose insulin resistance.
Results: We calculated IC50 using plasma insulin concentrations measured under baseline, low and high insulin dose (IC50 BLH), baseline and low insulin dose (IC50 BL), or baseline and high insulin dose (IC50 BH) conditions. The IC50 BL values were less than IC50 BLH for 34 of 50 multi-step insulin clamp studies, indicating that the IC50 BLH value underestimated insulin sensitivity. Furthermore, the pattern of difference was such that relative underestimate of insulin sensitivity using the IC50 BLH vs. IC50 BL approach was greatest in those who were most insulin sensitive. IC50 BH was generally greater than IC50 BLH.
Conclusion: Optimal assessment of adipose insulin regulation of FFA release is obtained using a multi-step insulin clamp with a low insulin dose. The IC50 BLH approach needs to be scrutinized, especially in insulin sensitive individuals, to be able to detect small differences or changes in adipose tissue insulin action.

Disclosure
Y. Song: None. K. Lytle: None. M.D. Jensen: Advisory Panel; Biohaven.
2074-LB: Metabolic Heterogeneity of Adipocytes during Obesity Revealed by Single Nucleus RNA-seq
Authors: WEN SHIYI , XIONG NA , CHEN YANMING , LI SHASHA , SHI GUOJUN 
Published: June 2024

Objective: The prevalence of obesity continues increasing nowadays, but the understanding on the pathogenesis of obesity and its complications remains obscure. Adipocytes are the main components of metabolic homeostasis, involved in glucose and lipid metabolism, hormone and adipokine secretion. Previous studies show that adipocytes manifest high heterogeneity within white adipose tissue (WAT). Obesity changes the living environment of adipocytes. Thus, to investigate the potential impact of adipocytes metabolic changes towards obesity-related metabolic disorder, we explored the metabolic features of adipocytes through single nucleus RNA-seq (snRNA-seq) data and patients under bariatric surgery.
Methods: The snRNA-seq data of WAT from patients across a range of body weight were obtained from the GEO database, and genes related to metabolic pathways were extracted from the genome. Using single-cell data reduction and clustering tools to explore the metabolic signatures of adipocytes and cellular function. In addition, the differences in metabolic pathways of adipocytes and the expression levels of molecular targets were verified in other publicly available bulk RNA-seq data and WAT of patients undergoing bariatric surgery in our clinical center.
Results: 1) Human white adipocytes can be divided into 13 subgroups with unique metabolic signatures by snRNA-seq clustering. 2) Adipocytes enriched in the “cofactors and vitamins metabolism” were decreased, and the lipid hormone metabolic adipocytes increased in individuals with obesity. 3) The signatures of “cofactors and vitamins metabolism” showed positive correlation with the activity of leptin response pathway.
Conclusion: Human white adipocyte subgroups manifest high metabolic diversification within WAT of individuals across a range of body weight. Our study suggests that the "cofactors and vitamins metabolism" might be a potential therapeutic strategy for treating obesity.

Disclosure
Y. Chen: None.
208-OR: Impact of Carbohydrate-Restricted Nutrition Therapy and Continuous Remote Care among People with Type 2 Diabetes in Rural vs. Urban Areas
Authors: ATHINARAYANAN SHAMINIE J. , ADAMS REBECCA N. , ROBERTS CAROLINE G.P. , VOLK BRITTANIE M. , ZOLLER ALISON , MCKENZIE AMY L. 
Published: June 2024

Diabetes outcomes and complications are often worse in rural (R) versus urban (U) areas, commonly due to challenges accessing health services. Our telemedicine clinic aims to address these barriers, offering carbohydrate-restricted nutrition therapy via continuous remote care for people with type 2 diabetes (T2D) nationwide. This retrospective analysis assessed the 1 year (y) effects of this care model on cardiometabolic markers in people with T2D from R and U counties. 74.7% R and 74.1% U were enrolled at least 1y in the clinic at time of analysis; a random sample of 800 was identified from each cohort. Changes from enrollment (E) to 1y were assessed with linear mixed effect models or logistic regression, as appropriate. Characteristics at E were consistent between R and U (Table 1). No differences between R and U areas were observed (ps&gt;0.05). In both R and U at 1y, HbA1c, weight, HDL-C, triglycerides, and liver enzymes improved, total cholesterol was unchanged, and LDL-C slightly increased within normal limits. There was no difference between R and U in attainment of HbA1c &lt;8% and LDL-C &lt;100 mg/dL at E and 1y. Patients in R areas were 20% less likely [OR: 0.80 (0.64, 0.99), p=0.04] to attain TG&lt;150 mg/dL vs U at E, but after 1 y, this disparity was closed [OR: 0.85(0.67, 1.08)]. These results show that this care model improves real-world cardiometabolic health in T2D in R and U areas.

Disclosure
S.J. Athinarayanan: Employee; Virta Health Corp. R.N. Adams: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. C.G.P. Roberts: Other Relationship; Virta Health Corp. B.M. Volk: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A. Zoller: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.L. McKenzie: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. Employee; Abbott.
2085-LB: Alleviation of Instant Blood-Mediated Inflammatory Reaction in Human Islets with Aptamers
Authors: KALIVARATHAN JAGAN , BALAJI SARAVANAN PRATHAB , FUGLESTAD BRIAN A. , DHAKAL SOMA , MOHAMMED SHUJAUDDIN , LEVY MARLON F. , KANAK MAZHAR A. 
Published: June 2024

Introduction and Objective: The instant blood-mediated inflammatory reaction (IBMIR) is a major factor that causes damage to transplanted islets. The blockade of pro-inflammatory mediators is a promising approach to improve islet engraftment. We hypothesized that blocking of key pro-inflammatory proteins by aptamers will dampen the IBMIR response and promote islet graft survival. We evaluated the blockade of inflammatory proteins such as interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNFα) using surface immobilization of aptamers (IL-1βApt, and TNFαApt) with bissulfosuccinimidyl suberate (BS3).
Methods: Initially toxicity studies were performed using human islets and beta cell lines. Further, human islets were exposed to cytokine cocktail (IL-1β, TNFα and IFNγ) in the presence and absence of individual and combined aptamers free and surface-immobilized aptamers. Gene expression of pro inflammatory cytokines were tested by qPCR analysis. Apoptotic genes were also measured to investigate the anti-apoptosis effect of aptamers.
Results: Toxicity studies with aptamers showed that IL-1βApt and TNFαApt up to 100µM concentrations were safe for cells and showed excellent anti-inflammatory effects in vitro. Both IL-1βApt and TNFαApt reversed the upregulation of proinflammatory genes induced by IL-1β and TNFα in the human islets respectively, and this was comparable to established IL-1β and TNFα antagonists. Further, we immobilized the aptamers on the surface of the islets and noticed that surface-immobilized aptamers have potent anti-inflammatory, and anti-apoptotic properties. Our results clearly show that aptamers are functional even after immobilization on the islet’s surface.
Conclusion: The current study offers a new potential target to improve islet engraftment and pave the way for further studies to better determine the role of these aptamers in allogeneic settings in combination with a well-established immune-suppressive platform.

Disclosure
J. Kalivarathan: None. P. Saravanan: None. B.A. Fuglestad: None. S. Dhakal: None. S. Mohammed: None. M.F. Levy: None. M.A. Kanak: None.

Funding
Department of Defense (W81XWH2210102)
2099-LB: Increased Expression of PFKFB3 in Diabetic Pancreatic ß-Cells May Compensate for the Maintenance of Glucose Metabolism
Authors: CHIBA KOKI , NOMOTO HIROSHI , IZUMIHARA RIMI , KAMEDA HIRAKU , NAKAMURA AKINOBU , ATSUMI TATSUYA 
Published: June 2024

Background: In diabetic pancreatic β-cells, glycolysis is activated, and the up-regulation of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) has been suggested to be involved in these intracellular metabolic changes, but its physiological significance remains unclear. This study aims to clarify the role of PFKFB3 up-regulation in pancreatic β-cells under diabetic conditions.
Methods: Streptozotocin (STZ)-induced diabetic C57B6/J mice were divided into two groups: mice receiving the PFKFB3 inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), and their control group. The body mass, glucose tolerance and insulin secretion were compared among the groups. PFKFB3 and MafA expressions in pancreatic islets were assessed through immunostaining. INS-1 cells were cultured for 48 hours in either 5.5mM or 22mM glucose conditions with or without Pfkfb3 gene silencing and compared for gene expression and glucose-responsive insulin secretion.
Results: The inhibition of PFKFB3 by 3PO resulted in a reduction of insulin secretion during high glucose stimulation and exhibited elevated blood glucose levels, indicating impaired glucose tolerance. STZ increased the PFKFB3 expression in pancreatic islets, but it was decreased by 3PO administration. The expression of MafA in pancreatic islets decreased after STZ administration, and it was further impaired with 3PO administration. In INS-1 cells, the expression of Pdx-1 and Mafa decreased under high glucose conditions, and silencing Pfkfb3 did not affect this change. However, knockdown of Pfkfb3 led to decreased insulin secretion in response to high glucose stimulation.
Conclusion: The inhibition of PFKFB3 in diabetic condition worsened insulin secretion and glucose tolerance, suggesting a potential role in compensating for glucose tolerance.

Disclosure
K. Chiba: None. H. Nomoto: Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk. Research Support; Kowa Company, Ltd. R. Izumihara: None. H. Kameda: None. A. Nakamura: Research Support; Kowa Company, Ltd. Speaker's Bureau; Novo Nordisk, Taisho Pharmaceutical Holdings Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation. Research Support; Abbott Japan Co., Ltd., Boehringer-Ingelheim. T. Atsumi: None.
227-OR: Tirzepatide Reduces HbA1c and Body Weight Significantly More than Placebo Regardless of Insulin Sensitivity and Beta-Cell Function—Post Hoc Analysis from SURMOUNT-2
Authors: HEISE TIM , WANG HUI , MAST CASEY J. , BENABBAD IMANE , LEE CLARE , LIAO BIRONG 
Published: June 2024

Treatment with tirzepatide (TZP) led to substantial improvements in body weight (BW) and glycemia compared to placebo in participants with obesity and type 2 diabetes (T2D) in SURMOUNT (SM)-2. In this analysis, we assessed whether baseline markers of pancreatic beta cell function and insulin sensitivity were associated with the magnitudes of BW and glycemic reductions. Post hoc analyses examined changes from baseline in BW and HbA1c in SM-2 at 72 weeks across HOMA2-B (computed with C-peptide) and HOMA2-IR (computed with insulin) quartiles (Q) from low (lower beta cell function/insulin resistance) (Q1) to high (Q4) as assessed by a mixed model for repeated measures using efficacy estimand. BW and HbA1c reductions were greater with TZP 10 mg and 15 mg than placebo within each HOMA2-B and HOMA2-IR baseline Q. More participants across all Qs achieved ≥15% BW reduction with TZP (36-63%) than placebo (up to 4%). More participants across all Qs reached HbA1c &lt;5.7% with TZP (ranging from 42-71%) than placebo (up to 6%). TZP was more effective than placebo in reducing BW and HbA1c regardless of beta cell function and insulin resistance in participants with obesity and T2D. BW reductions with TZP trended greater with higher beta cell function, whereas HbA1c reduction trended greater with lower beta cell function.

Disclosure
T. Heise: Research Support; ADOCIA, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk A/S. Consultant; Gan&Lee Pharmaceuticals. Speaker's Bureau; Eli Lilly and Company. Research Support; Altimmune Inc., Sanofi, Zealand Pharma A/S, BIOTON, Civica Foundation, Enyo Pharma, Gan&Lee Pharmaceuticals, Nanexa AB, SamChunDang Pharm. Co. H. Wang: None. C.J. Mast: Employee; Eli Lilly and Company. I. Benabbad: Employee; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Liao: Employee; Eli Lilly and Company.