bluuebunny/crossref_metadata_2025 huggingface dataset:
1789-LB: Prevalence of Atherosclerotic Cardiovascular Disease in Adults with Type 2 Diabetes in Jordan—The PACT-MEA Study
Authors: ABBAS FIRAS O. , ABBASI HIBA , ABU ALSAMEN MUNEER A. , ALMOUSA EYAS N. , AMMARI FAWAZ L. , HADDAD JIHAD A. , HADDAD SUHAIR E. , JARADAT MUSTAFA , KHASSAWNEH ADI , KHATIB NIDAL , MAGABLEH ARABIEH , HADDAD FARES H.
Published: June 2024

Introduction & Objective: Globally, nearly one-third of people with type 2 diabetes (T2D) has a type of cardiovascular (CV) disease, the majority of which is atherosclerotic cardiovascular disease (ASCVD). To address the lack of representative data regarding these conditions in Middle Eastern and African (MEA) countries, we aimed to assess the prevalence of established atherosclerotic cardiovascular disease (eASCVD) and ASCVD risk in patients with T2D in seven countries across the Middle East and Africa. Here we present the primary results for Jordan to identify opportunities for improving T2D management in this country.

Methods: PACT-MEA (PACT-MEA; NCT05317845) is a cross-sectional, observational study of adults (≥18 years) with T2D from primary and secondary care settings. During scheduled clinic visits in 2022, medical history, demographic, clinical, laboratory, and pharmacotherapy data were extracted from medical charts of patients. We report the prevalence (95% CI) of eASCVD and ASCVD risk using the risk category definitions of moderate, high, very high (latter includes eASCVD) from the 2021 European Society of Cardiology (ESC) Guidelines on CV Disease Prevention in Clinical Practice.

Results: A total of 576 patients with T2D in Jordan were enrolled across ten study sites. The mean patient age was 59.7 and included 52% males and 48% females. Patients were enrolled from primary and secondary care settings (28% and 72%, respectively). A total of 151 patients with T2D had eASCVD, corresponding to a prevalence of 26.2% (95% CI: 22.8-30.0). Per ESC guidelines, 0.8% of people with T2D in Jordan were at moderate risk for ASCVD, 66.0% were at high risk, and 33.3% were at very high risk.

Conclusion: Our findings indicate that eASCVD is prevalent in more than one-quarter of people with T2D in Jordan, and nearly all are at high/very high ASCVD risk. This suggests there is an opportunity for improved screening and management of T2D to reduce CV risk in this country.

Disclosure

F.O. Abbas: None. H. Abbasi: None. M.A. Abu Alsamen: None. E.N. Almousa: None. J.A. Haddad: None. S.E. Haddad: None. M. Jaradat: None. A. Khassawneh: None. N. Khatib: None. A. Magableh: None. F.H. Haddad: None.

Funding

Novo Nordisk, Inc.
1828-LB: A Correlational Study on Improving Patients’ Cognition of Diabetes and Long-Term Reversal of Diabetes
Authors: WANG YAO
Published: June 2024

Objective: Type 2 diabetes can be reversed through lifestyle intervention, but the long-term reversal rate is low. This study aims to explore how to improve patients' cognition of diabetes and cultivate a healthy lifestyle, and investigate its correlation with long-term diabetes reversal.

Methods: A total of 200 patients with early type 2 diabetes mellitus complicated with obesity were randomly selected and reversed diabetes through weight loss. They were randomly divided into a control group (Group A with 100 patients, weight loss + routine health education) and an intervention group (Group B with 100 patients + cognitive training). Group A received routine health education, while Group B received offline training + examination + artificial intelligence online diabetes knowledge education once a week for 12 weeks, with a one-year follow-up. Blood glucose, HbA1c, pancreatic function, body weight, body fat rate, muscle mass, and other related indicators were monitored in both groups. The differences in long-term reversal rates and related indicators between the two groups were analyzed.

Results: The intervention reversal rate in Group A was 46% at 12 weeks and 28% at one year; while in Group B, it was 62% at 12 weeks and 36% at one year. There were significant differences in short-term and long-term reversal rates between the two groups (P<0.05). There were differences in cognitive scores between the two groups, with a score of 60.1±2.9 in Group A and 66.0±1.8 in Group B. Cognitive scores were positively correlated with long-term diabetes reversal rates.

Conclusion: Improvement in cognitive behavior among patients with type 2 diabetes is associated with increased long-term diabetes reversal rates, increased muscle mass, and decreased body fat rates.

Disclosure

Y. Wang: None.
1847-LB: Fear of Hypoglycemia and Sleep among Parents of Young Children with Type 1 Diabetes
Authors: CAMPBELL MARYJANE , MONZON ALEXANDRA , CLEMENTS MARK A. , PATTON SUSANA R.
Published: June 2024

Background: Parents’ fear of hypoglycemia (FH) is common and associated with increased parental anxiety and stress. We examined the associations among FH and parental sleep in a sample of parents of young children with type 1 diabetes (T1D). We additionally explored whether FH and parental sleep differed by insulin modality or associated with child age and T1D duration.

Methods: One hundred and eighty-four parents completed the Hypoglycemia Fear Survey-Parent (HFS-PYC), the PROMIS Sleep Disturbance Short Form, and reported on their child’s T1D, insulin pump usage, and frequency of hypoglycemia.

Results: Parents were 92% mothers (M age=36.43±6.11) and children were 45% female (M child age=4.40±1.23; M HbA1c=7.54%±1.15). Children included 49% on a hybrid closed loop pump (HCL), 29% on an open loop pump (OLP), and 23% on multiple daily injections (MDI). Parent-reported FH (M=76.66±16.58) was associated with greater parental sleep disturbance and greater frequency of hypoglycemic events (>2/week). Parents of youth on HCL reported greater difficulty staying asleep compared to parents of youth on MDI (p<.05), but not compared to parents of youth on OLP (p>.05). FH did not differ based on insulin modality. FH and sleep disruption were not associated with T1D duration or child age.

Conclusions: FH may contribute to disrupted sleep among parents of young children with T1D regardless of insulin modality, tT1D duration, or child age. Parents who reported greater FH were more likely to report greater frequency of hypoglycemic events; however, it is unclear whether parent-reported hypoglycemic events occurred during the night, contributing to disrupted sleep. Further, HCL usage was associated with sleep disruption, but not FH. Future research that incorporates continuous glucose monitoring and assesses parental FH specifically at night will help identify factors that may contribute to disrupted parental sleep and thereby help inform future sleep-promoting interventions for these parents.

Disclosure

M. Campbell: None. A. Monzon: None. M.A. Clements: Research Support; Abbott. Consultant; Glooko, Inc. Research Support; Dexcom, Inc. S.R. Patton: None.

Funding

National Institutes of Health (R01DK118514)
1860-LB: Preliminary Study of Efficacy and Duration of an mRNA-Based GLP-1R Agonist in Diabetic Monkeys
Authors: XU FENGWEI , WU KANGZENG , ZHANG LEI , DAI YONGCHAO , XU YUHONG
Published: June 2024

HFG1 is an mRNA based GLP-1R agonist encoding a fusion protein of a GLP-1 analogue and a pH sensitive binder of human FcRn. The mRNA is encapsulated inside lipid nano-structures (LNPs) designed for subcutaneous gene delivery and local transfection, and the proteins expressed would be secreted and distributed into systemic circulation. In order to characterize the HFG1 activities in vivo, five monkeys with naturally occurred diabetes (FPG≥9.69 mg/dl, HbA1c≥5.6%) were selected to receive one subcutaneous injection of LNPs of slightly variable compositions containing about 0.5-1.0mg mRNA. The monkeys were closely monitored for 60 days and no behavior changes were observed except that they all had greatly reduced food uptake on the first few days after injection. By D56 they lost an average of 0.22kg each. Blood samples were collected at various time points and assayed in a GLP-1R/CRE Luciferase Reporter Cell system for GLP-1 equivalent activities. Figure 1 plotted the individual measurements (solid dots) and average value changes (solid line). The HbA1c% levels were assayed by Suzhou Xihua Scientific Co. and shown as open squares. Even though some time points are missing (TBD), the trend of HbA1c% reduction after a single HFG1 injection is significant.

Disclosure

F. Xu: Employee; highfield. K. Wu: Employee; high field. L. Zhang: Employee; HighField Biopharmaceuticals Corporation. Y. Dai: Employee; HighField Biopharmaceuticals Corporation. Y. Xu: Employee; Hangzhou HighField Biopharm. Stock/Shareholder; Hangzhou HighField Biopharm.
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 <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<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<0.001). Other secondary endpoints at Week 24 also favored iGlarLixi vs IDegAsp, respectively (p<0.001 for all): HbA1c <7.0% (72.5% vs 59.8%); HbA1c <7.0% + no BW gain (40.5% vs 21.3%); HbA1c <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 < 0.0001) after 13 weeks, 111.42 ± 14.42 (p < 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 >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 <65 and ≥65 years old. Two subgroups were analyzed: <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>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 <8% and LDL-C <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<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 <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.
286-OR: JNK3—A Key Downstream Target of Incretin Responses in ß-Cells
Authors: ANDRADE LOUZADA NETO RUY , GONZALEZ MAREL , PITA-GRISANTI VALENTINA , BLANDINO-ROSANO MANUEL , BERNAL-MIZRACHI ERNESTO
Published: June 2024

The c-Jun N-terminal Kinases (JNKs) regulate crucial physiological processes. JNK1 and JNK2 exhibit broad tissue distribution and are implicated in insulin resistance, inflammation, and cell signaling. Conversely, JNK3 (MAPK10) is predominantly found in CNS neurons and pancreatic β- cells and the physiological function of this JNK member is less understood. To explore JNK3's role in pancreatic β-cells, we generated mice with JNK3 deletion in beta-cells (βJNK3KO). βJNK3KO exhibited glucose intolerance and insulin secretion only after oral, suggesting a role for JNK3 in incretin responses. Assessment of incretin responses demonstrated impaired insulin secretion induced by Exendin 4 (Ex4) in βJNK3KO and this was associated with reduced GLP1R expression. These findings were validated in human islets treated with a specific JNK3 inhibitor (iJNK3). Downstream of GLP1-R, CREB phosphorylation upon Ex4 was decreased in βJNK3KO islets suggesting a crosstalk between JNK3 and GLP1-R signaling on regulation of acute insulin secretion by incretins. Notably, GLP1R/cAMP/CREB axis induction of IRS2 expression, a master regulator of β-cell survival and growth, was also downregulated in βJNK3KO mice and human islets treated with iJNK3. As a result of decreased IRS2 expression, the protective effect of Ex4 was lost in βJNK3KO islets exposed to proinflammatory cytokines and human islets treated with iJNK3. Finally, the beneficial protective effect of Ex4 treatment was partially attenuated in βJNK3KO in a model of multiple low doses of STZ.

In conclusion, our data identify JNK3 as a novel player in β-cell function and survival and suggest that JNK3 presents a potential therapeutic alternative for incretin-based therapy.

Disclosure

R. Andrade Louzada Neto: None. M. Gonzalez: None. V. Pita-Grisanti: None. M. Blandino-Rosano: None. E. Bernal-Mizrachi: None.

Funding

Grants R01-DK073716, DK132103 and DK133183
295-OR: The PNPLA3 G-allele Reduces the Beneficial Effects of a Healthy Diet on Hepatic Lipid Content in Type 2 Diabetes
Authors: PAFILI KALLIOPI , ZAHARIA OANA P. , STRASSBURGER KLAUS , KNEBEL BIRGIT , HERDER CHRISTIAN , HUTTASCH MAXIMILIAN , KARUSHEVA YANISLAVA , KABISCH STEFAN , STROM ALEXANDER , SZENDROEDI JULIA , RODEN MICHAEL
Published: June 2024

Introduction & Objective: Weight loss is pivotal for, but variably effective in type 2 diabetes (T2D) and comorbidities. The G-allele in the rs738409 single nucleotide polymorphism within the patatin-like phospholipase domain-containing protein 3 (PNPLA3) associates with liver steatosis and differently with insulin resistance. We hypothesized that this G-allele may affect response to dietary interventions.

Methods: T2D volunteers (age 18-69 years, BMI ≥30 kg/m2, HbA1c <9.0%) were randomly assigned to 8-w hypocaloric diets (1.256 kJ reduction in total daily energy intake), either high in cereal fiber and coffee, but red meat-free (healthy diet [HD]; n=16), or low in fiber, devoid of coffee, but rich in red meat (unhealthy diet [UD]; n=15). Genotyping was performed for the PNPLA3 gene. Insulin sensitivity (M-value) was measured by hyperinsulinemic-euglycemic clamps, hepatic lipid content (HCL) by 1H magnetic resonance spectroscopy before and after the intervention.

Results: Baseline HCL was similar between groups (carriers: UD 18.5±8.5%, HD 14.6±8.4%; non-carriers: UD 13.5±4.2%, HD 17.8±7.3%). In the face of comparable body weight reduction (~4.7%), carriers and non-carriers decreased HCL from 0 to 8 weeks of UD (-57% and -46%, p<0.05), with no difference between groups. HD also led to reduction in HCL in non-carriers, but to lesser extent in carriers (-65% vs. -36%, p<0.05 vs baseline and between groups). Changes from baseline in liver fibrosis markers (fibrosis-4 index, AST/platelet ratio index, Forns score) and inflammation (interleukins) did not differ by carrier status. M-value improved in all groups (carriers +27% and non-carriers +21% on HD and carriers on UD +37%, all p<0.05 vs baseline) except for the non-carriers on UD.

Conclusion: Low-energy diets improve insulin sensitivity and steatosis in T2D but the presence of the G allele of PNPLA3 reduces the beneficial effects of a healthy (cereal- and coffee-enriched, but red meat-free) diet on liver lipid content.

Disclosure

K. Pafili: None. O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. C. Herder: None. M. Huttasch: None. Y. Karusheva: None. S. Kabisch: Other Relationship; Sanofi, Boehringer-Ingelheim, Berlin-Chemie AG. Research Support; J. Rettenmaier & Söhne, Rosenberg, Germany, California Walnut Commission, Almond Board of California, Wilhelm-Doerenkamp-Foundation. Other Relationship; JuZo-Akademie, Lilly Diabetes. A. Strom: Consultant; Wörwag Pharma. J. Szendroedi: None. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca.
300-OR: Beneficial Effect of the Combination Therapy of Cagrilintide, a Dual Amylin/Calcitonin Agonist, and Tirzepatide, a Dual GLP-1/GIP Agonist, on Body Weight Loss in Obese Rats
Authors: VALDECANTOS PILAR , RADA PATRICIA , GHOSH SOUMITRA , RONDINONE CRISTINA M. , VALVERDE ANGELA M.
Published: June 2024

Introduction & Objective: Combinatorial therapies with incretin receptor agonists targeting multiple pathways that regulate energy balance is a promising strategy for weight loss since it potentially allows dose reduction of each drug and can help to ameliorate the associated gastrointestinal side-effects of the current monotherapies. We evaluated the combination of cagrilintide and tirzepatide on weight loss in obese rats.

Methods: Diet-induced obese Sprague Dawley male rats were dosed subcutaneously once-daily for 12 days with 3 and 10 nmol/kg of cagrilintide and tirzepatide alone or in combination at submaximal dose of 3 nmol/kg. Body weight and food intake were measured daily. Biochemical parameters in plasma were analyzed.

Results: Relative to vehicle, cagrilintide administered alone presented superior efficacy in body weight reduction (-7.22%±1.80% at 3 nmol/kg and -9.61% ± 0.52% at 10 nmol/kg) compared with tirzepatide (-2.53% ± 0.44% at 3 nmol/kg and -5.81 ± 0.86% at 10 nmol/kg). Peptide combination at submaximal dose of 3 nmol/kg each reduced body weight by -11.0 ± 0.86% (P<0.05 vs cagrilintide and P<0.001 versus tirzepatide) at the same doses, Reductions in cumulative food intake correlated with weight loss. Combination therapy was superior in decreasing ALT than cagrilintide (P<0.001) and tirzepatide (P<0.05) and plasma TGs levels were lower compared to the tirzepatide group (P< 0.001).

Conclusion: Combination therapy at submaximal doses of cagrilintide and tirzepatide achieved significantly greater weight loss and higher reduction in food intake compared to the monotherapy, suggesting the potential opportunity of this combination for further clinical development.

Disclosure

P. Valdecantos: Research Support; Pep2Tango Therapeutics INC. P. Rada: Research Support; Pep2Tango Therapeutics INC. S. Ghosh: Consultant; Abvance Therapeutics, Akero Therapeutics, Inc., Fractyl Health, Inc., Takeda Pharmaceutical Company Limited. C.M. Rondinone: Board Member; Pep2tango Therapeutics Inc. Stock/Shareholder; Pep2tango Therapeutics Inc. A.M. Valverde: Research Support; Pep2Tango Therapeutics INC.

Funding

Pep2Tango Therapeutics INC
301-OR: Synergistic Effects of Dapagliflozin and Tirzepatide Combination Treatment on Weight Loss and Glucose Regulation in Diet-Induced Obese Animals
Authors: ABU-FARHA MOHAMED , AL-KHAIRI IRINA , QADDOUMI MOHAMMAD , ALAJMI FAHAD , ABUKHALAF NERMEEN A. , CHERIAN PREETHI T. , AREFANIAN HOSSEIN , ABUBAKER JEHAD , ABDUL-GHANI MUHAMMAD , AL-MULLA FAHD
Published: June 2024

Background: Tirzepatide is a dual GLP-1 and GIP receptor agonist that enhances glucose-stimulated insulin secretion and significantly lowers HbA1c as well as weight. SGLT2 has also been shown to reduce weight in addition to their glucose lowering effect. Given their different modes of action we hypothesized that their combination would produce additive improvements in weight loss as well as their glycemic control.

Methods: A total of 40 male Sprague Dawley rats aged 6-8 weeks were fed a Normal Diet or high-fat cafeteria diet for 12 weeks. Animals on high fat diet were then divided into four groups treated with either placebo, 100 nmole/kg Tirzepatide, Dapagliflozin 1mg/kg or a combination of Dapagliflozin and Tirzepatide for 6 weeks. Weight, FBG, and calorie consumption were monitored on a weekly basis. The study concluded with the administration of OGTT and ITT tests, followed by the collection of various tissues.

Results: After treatment, animals on normal diet weight of 522.9±11.7g, placebo-treated obese animals were 671.3 ± 26.2g, compared to 598.9 ± 23.4g in dapagliflozin-treated, 532.3±23.0g in Tirzepatide-treated animals, and 480.7± 18.8 g in animals treated with the combination (p<0.001). The addition of dapagliflozin to Tirzepatide resulted in a significant additive improvement in glucose AUC compared to Tirzepatide alone. Moreover, omental, and subcutaneous adipose tissue weight was significantly decreased in animals treated with the combination compared to Tirzepatide alone.

Conclusion: The addition of dapagliflozin to tirzepatide resulted in further weight reduction and improvement in glycemic control compared to each drug alone.

Disclosure

M. Abu-Farha: None. I. Al-khairi: None. M. Qaddoumi: None. F. Alajmi: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. N.A. Abukhalaf: None. P.T. Cherian: None. H. Arefanian: None. J. Abubaker: None. M. Abdul-Ghani: None. F. Al-Mulla: None.

Funding

Kuwait Foundation for the Advancement of Sciences
314-OR: A Randomized Study of a GPR119 Agonist on Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes Mellitus (T1DM)
Authors: BILAL ANIKA , CASU ANNA , YI FANCHAO , MUCINSKI JUSTINE M. , MERCOUFFER GINA , KELLEY DAVID E. , PRATLEY RICHARD E.
Published: June 2024

Introduction: Activation of GPR119 receptors (expressed on enteroendocrine and pancreatic islet cells) augments glucagon counter-regulatory responses to hypoglycemia in pre-clinical models. This response is studied using MBX-2982, a GPR119 agonist, in participants with T1D.

Methods: This phase 2a double-blind, cross-over study randomized participants (age;20-60 years, T1D diagnosis ≥5 years) to treatment with 600 mg MBX-2982 or placebo for 14 days with two weeks washout between periods. The study endpoints included glucagon response, epinephrine response, and endogenous glucose production during a euglycemic/hypoglycemic clamp. Glucagon, GLP-1, and GIP in response to a mixed meal test and glycemic metrics from continuous glucose monitor (10 days) were also measured.

Results: 18 participants (age 38.3±12 years, 50% females, 88.9% White, A1c 7.0±0.8%) were enrolled. Compared to placebo, MBX-2982 did not alter counter-regulatory responses to insulin-induced hypoglycemia. GLP-1 response to the MMT were higher following MBX-2982 administration. (Table)

Conclusion: GPR119 activation with MBX-2982 did not improve glucagon counterregulatory responses to hypoglycemia in participants with T1D. The significant increases in fasting GLP-1 and responses during the MMT are consistent with GPR119 target engagement and the expected pharmacodynamic response from L-cells.

Disclosure

A. Bilal: None. A. Casu: None. F. Yi: None. J.M. Mucinski: None. G. Mercouffer: None. D.E. Kelley: Consultant; Pramana Pharmaceuticals, Inc. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc.

Funding

The Helmsley Charitable Trust, CymaBay Therapeutics.
339-OR: Enhanced Expression of Zinc Finger Protein 385D Leads to Type 2 Diabetes Phenotype in Human Beta Cells
Authors: LU GEMING , KANG RANDY , VARELA MIGUEL A. , OH EUNJIN , THURMOND DEBBIE C. , GARCIA-OCANA ADOLFO
Published: June 2024

Identification of molecular mechanisms that regulate glucose-stimulated insulin secretion (GSIS) and β-cell identity and growth are essential to develop therapeutic approaches to treat diabetes. Zinc finger protein 385D (ZNF385D) is a nuclear protein that belongs to the Krüppel C2H2-type zinc-finger protein family. Gene-Wide Association Studies have strongly associated ZNF385D gene variants with type 2 diabetes (T2D) onset. Using scRNA-seq and snRNA-seq of adult nondiabetic human islets, we have recently reported that the ZNF385D gene is specifically expressed in human β cells, and its expression negatively correlates with INS expression. However, the role of ZNF385D in the human β cell is unknown. Here, we have addressed this point by overexpressing ZNF385D in EndoC-βH1 cells and human islets and analyzed gene expression, GSIS, and β cell survival. Mining of scRNA-seq data from human islets of nondiabetic and T2D donors from HIRN-HPAP showed that ZNF385 expression is significantly enhanced while INS expression is significantly decreased in β-cells of T2D islets. Overexpression of ZNF385D in EndoC-βH1 cells and human islets led to significant downregulation of INS, PDX1, MAFA, SLC2A2, SNAP25 and VAMP2 genes and significant upregulation of T2D β-like genes such as RFX7, PPAR γ, PPAR α, RB1, POU5F1, NANOG and MYCL. ZNF385D overexpression significantly reduced GSIS without altering basal secretion. scRNA-seq analysis of human islets showed a positive correlation between ZNF385D expression and activation of senescence, apoptosis and metabolic inflexibility pathways in β-cells. Indeed, β-cell death was significantly enhanced by ZNF385D overexpression after treatment with cytokines (TNFα, IL1β, and IFNγ) as assessed by flow cytometry and TUNEL staining. Taken together, these studies indicate that enhanced expression of the β-cell specific gene ZNF385D causes detrimental effects in the function, identity and survival of the human β-cell leading to a T2D-like phenotype.

Disclosure

G. Lu: None. R. Kang: None. M.A. Varela: None. E. Oh: None. D.C. Thurmond: Consultant; Truebindings. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd.

Funding

AR-DMRI Innovative Award
34-PUB: Prescription Pattern of SGLT-2 Inhibitors among Seniors with Type 2 Diabetes Mellitus and Chronic Kidney Disease in a Primary Care Setting
Authors: NAOUS ELIE , ELNAJJAR MAYSSAM , ALHADDAD JULIANO , ACHKAR ANGELA , JABER BERTRAND L. , HE ZHIHENG
Published: June 2024

Background: SGLT-2 inhibitors (SGLT2i) remain under-prescribed in eligible patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM), despite of its proven efficacy in renal protection. Data in geriatric population lacks.

Methods: As part of a quality improvement project, this baseline cross-sectional evaluation assesses SGLT2i prescription rates in seniors (age ≥65 years old), with T2DM and CKD stages 3-4 (eGFR 20-59 mL/min/1.73 m2) at a primary care clinic (August to November 2023).

Results: Eighty-one eligible patients were included, 56.8% were women. Mean (±SD) age was 81.7 ± 8.2 years old. Mean HbA1c was 7.1 ± 1.2%, and mean eGFR was 42.4 ± 10.9 ml/min/1.73m². Notably, 11% were not screened for proteinuria in the prior year, and 47.2% of screened individuals exhibited proteinuria. As shown in table 1, SGLT2i were prescribed in 40.7% of patients with CKD, but their use was significantly higher among patients with vascular disease (72.7%), heart failure (57.6%), and those requiring insulin (42.4%).

Conclusion: In a primary care clinic, SGLT2i were prescribed in 40.7% of seniors with T2DM and CKD but were commonly used among patients with cardiovascular diseases and those requiring insulin. Further investigation is needed to understand this gap in knowledge and formulate a mitigation strategy to expand SGLT2i use in eligible patients.

Disclosure

E. Naous: None. M. Elnajjar: None. J. Alhaddad: None. A. Achkar: None. B.L. Jaber: Other Relationship; Up-To-Date. Consultant; Avania, LLC (Ad Hoc Member, Clinical Events Committee). Z. He: None.