bluuebunny/crossref_metadata_2025 huggingface dataset:
319-OR: Renoprotective Effects of Glucagon and Incretin Agonist Combinations Mediated by Macula Densa Cells
Authors: GYARMATI GEORGINA , BECERRA CALDERON ALEJANDRA , IZUHARA AUDREY , KONKAR ANISH , DUFFIN KEVIN L. , DEY ASIM B. , PETI-PETERDI JANOS
Published: June 2024

Introduction & Objective: Recent therapeutic advances in diabetic nephropathy (DN) including GLP-1 analogs are promising, however more efficient treatments are needed with improved mechanistic understanding of their mode of action. Glucagon (GCG), GLP-1 and GIP receptors (R) are expressed in the kidney. Macula densa (MD) cells play central roles in controlling renal hemodynamics and tissue remodeling. This study aimed to examine the renoprotective effects of GCG w/without incretin analogs.

Methods: Intravital multiphoton imaging (MPM) was used to detect acute or chronic effects of GCG (long-acting IUB288) w/wo GLP-1 and GIP on afferent (AA) and efferent arteriole (EA) blood flow, single nephron glomerular filtration rate (SNGFR), MD cell calcium, nitric oxide (NO, using DAF-FM diacetate iv), mitochondrial function (using MitoTracker Red iv) in wild-type or Sox2-GCaMP5, Ren1d or Cdh5-Confetti mice (for genetic cell fate tracking) in control and STZ model of type I DN, and in MD cells in vitro.

Results: MPM revealed intense, selective MD cell labeling with AF647-conjugated GCG injected iv. GCG induced acute, two-fold increases in cell calcium only in MD cells. GCGR was 7.64-fold enriched in MD vs control cell transcriptome. Acute GCG treatment significantly increased MD cell protein synthesis, NO production, mitochondrial metabolism, AA/EA blood flow, protected glomerular hemodynamics from vasoconstrictor challenge. These effects were preserved or augmented when given in combination with incretin analogs including the GCG/GLP-1/GIP triagonist TG208, in chronic treatments and DN. Chronic GCG treatment induced a trend towards augmented tissue remodeling by resident progenitor cells.

Conclusion: MD-specific functional expression of GCGR is linked to improved cell metabolism, vasodilation, renal hemodynamics and tissue repair. MD cell targeting is an important novel mode of action of GCG that may be combined with incretin analogs for greater therapeutic effect in DN.

Disclosure

G. Gyarmati: Research Support; Traveere Pharmaceuticals. Other Relationship; Macula Densa Cell LLC. A. Becerra Calderon: None. A. Izuhara: None. A. Konkar: None. K.L. Duffin: Employee; Eli Lilly and Company. A.B. Dey: Employee; Eli Lilly and Company. J. Peti-Peterdi: Research Support; Traveere Pharmaceuticals. Other Relationship; Macula Densa Cell LLC.

Funding

Eli Lilly and Company
324-OR: Characterization of Aqueous Retinol Binding Protein 3 Concentrations and Diabetic Retinopathy Progression in Type 1 and Type 2 Diabetes
Authors: CHOKSHI TANVI , FICKWEILER WARD , VISHVA TEJA JANGOLLA SURYA , WU I-HSIEN , SUN JENNIFER K. , AIELLO LLOYD P. , KING GEORGE L.
Published: June 2024

Joslin Medalist Study identified Retinol Binding Protein 3 (RBP3) as a potential protective factor against advanced diabetic retinopathy (DR) in the vitreous and retina of people with type 1 diabetes for 50 years or longer. There is emerging interest in DR biomarker identification in aqueous due to its easier access compared to vitreous. Quantitive aqueous RBP3 concentration, in a pilot study, correlated inversely with DR severity, but positively with vitreous RBP3, suggesting it may be a clinically useful DR biomarker. This study measured RBP3 concentration in 153 aqueous samples from patients undergoing cataract surgery at the Joslin Beetham Eye Institute to characterize RBP3 concentrations in relation to DR progression. DR progression was defined as ≥2-step worsening on the Early Treatment Diabetic Retinopathy Study severity scale. At baseline, DR severity distribution was 36% no DR, 38% mild and 26% moderate DR. The average follow-up was 5.6±3.6yrs. Aqueous RBP3 concentration was highest in patients with no visible signs of DR (median 2.1nM) compared to mild and moderate DR (1.5nM, P=0.04). There was no significant difference between aqueous RBP3 concentration in those with type 1 or type 2 diabetes (P=0.55). DR progression was present in 28.1% (N=45). Elevated aqueous RBP3 concentration was associated with less frequent diabetic macular edema (Odd Ratio (OR) 0.20, 95% Confidence Interval (CI) 0.07;0.56, P=0.002). In unadjusted analyses, less DR progression was associated with older age (OR 0.87, CI 0.79;0.96, P=0.006), lower HbA1c (OR 1.88, 95% CI 1.01;3.49, P=0.05), and elevated RBP3 concentration (OR 0.51, 95% CI 0.28;0.93, P=0.029). The performance of an Area Under the Curve model including RBP3 was 0.69 for predicting DR progression. These findings indicate that elevated aqueous RBP3 concentration is associated with less DR progression, supporting its potential as a protective factor and retinal-specific DR biomarker.

Disclosure

T. Chokshi: None. W. Fickweiler: None. S. Jangolla: None. I. Wu: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. G.L. King: None.

Funding

American Diabetes Association (7-21-PDF-022); National Eye Institute (R01EYE26080-01), the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3- DK-094333-01); JDRF (17-2013-310); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund
33-OR: The Risk of Heart Failure Hospitalization after Initiation of SGLT2i, GLP-1RA, DPP-4i, or SUs in Patients with Type 2 Diabetes and Low-to-Moderate CV Risk
Authors: TESFAYE HELEN , PAIK JULIE M. , ALIX CAROLINE , JANE CROMER SARA , EVERETT BRENDAN M. , GLYNN ROBERT , WEXLER DEBORAH J. , PATORNO ELISABETTA
Published: June 2024

Introduction & Objective: Patients with type 2 diabetes (T2D) are at increased risk of heart failure (HF). There is limited guidance on which diabetes medications clinicians should use in patients without established cardiovascular disease (CVD) to address this risk.

Methods: Using Medicare and 2 U.S. private health plans (2013-2023), we identified six pairwise cohorts of 1:1 propensity score-matched patients aged ≥18 years (≥66 years in Medicare) with T2D without established CVD (atherosclerotic CVD or HF) who initiated SGLT2i, GLP-1RA, DPP-4i, or SU (Table), and estimated HRs and 95% CIs for the risk of hospitalization for HF [using 2 definitions based on a HF discharge diagnosis in the primary position (HHF-primary), or in any position (HHF-any)] and a composite of HHF or mortality, adjusting for 156 covariatesResults: Over a mean follow-up of ~11 months, the risk of HHF (either definition) was lower among SGLT2i initiators compared to all other classes (risk reduction 16-56%). Compared to DPP4i or SU, initiators of GLP-1RA also had lower risk of HHF (risk reduction 27-40%) (Table). Results were consistent for the composite outcome, driven by a decreased risk of HHF.

Conclusion: This study suggests that in patients with T2D and without established CVD, initiation of SGLT2i or GLP-1RA is associated with lower risk of HHF compared to other diabetes medications.

Disclosure

H. Tesfaye: None. J.M. Paik: None. C. Alix: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. B.M. Everett: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Ipsen Pharmaceuticals, Provention Bio, Inc. R. Glynn: Research Support; Amarin Corporation, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding

PCORI
335-OR: Preliminary Results of Islet Survival in a Novel Biovascular Pancreas Implanted in Primates
Authors: KURAL MEHMET H. , NASH KEVIN M. , NAEGELI KALEB M. , QIAN HONG , WANG JUAN , KIRKTON ROBERT D. , NIKLASON LAURA E.
Published: June 2024

Islet transplantation into the portal vein is currently regarded as the most promising therapeutic approach for reversing Type-1 diabetes. Nevertheless, islet loss due to inflammatory reaction, hypoxia, and peri-islet thrombosis, often hinders sustained insulin independence in most patients, despite the considerable number of islets utilized. In response to these constraints, we are focused on the development of an acellular biological vascular graft with an outer layer coated with an islet-populated hydrogel known as the Biovascular Pancreas or “BVP” (Fig. 1 A). When connected to arterial circulation, the BVP provides an oxygen-rich environment for the embedded islets due to blood flow through the BVP lumen. Previously, we demonstrated that the BVP can restore normoglycemia in diabetic rodent models with islet numbers as low as 1500 islet IEQ per rat. Recently, we generated BVPs made of 6-mm inner-diameter human acellular vessels (HAV) that are coated with a primate islet-populated fibrin layer and tested the islet engraftment in non-human primates. When implanted as an aortic bypass graft in a Cynomolgus macaque for two weeks, the BVP supported islet viability and insulin secretion (Fig. 1 B, C and D). Our results demonstrate the first primate implantation of the BVP and its potential to improve transplanted islet viability which will be evaluated via subsequent long-term in vivo studies.

Disclosure

M.H. Kural: None. K.M. Nash: Employee; Humacyte Inc. K.M. Naegeli: Employee; Humacyte Global, Inc. Stock/Shareholder; Humacyte Global, Inc. H. Qian: None. J. Wang: None. R.D. Kirkton: Employee; Humacyte, Inc. L.E. Niklason: None.

Funding

JDRF Industry Discovery and Development Partnership (IDDP) (3-IND-2023-1380-I-X)
35-OR: Lantidra, First FDA-Approved Cellular Therapy to Treat Type 1 Diabetes
Authors: RIOS PETER , MCGARRIGLE JAMES J. , LAMONICA GIOVANNA , LI YI , COOK JENNIFER , JOSHI IRA , GHANI SOFIA , COOK DAVID , LOPEZ DAISY , NASIR HAFSA , WANG YONG , OBERHOLZER JOSÉ
Published: June 2024

Despite intensive insulin therapy and frequent blood sugar monitoring, a subset of patients with type 1 diabetes (T1D) still suffer from debilitating symptoms, including severe hypoglycemia and hypoglycemia unawareness, and are left susceptible to the secondary complications of T1D. For T1D patients unable to achieve target hemoglobin A1c (HbA1c) despite intensive diabetes management and education, Lantidra is a treatment option to restore glycemic control, eliminate hypoglycemia episodes, and reduce or eliminate exogenous insulin injections. Lantidra is an FDA-approved allogeneic cellular therapy derived from donor pancreatic islet cells. Compared to whole pancreas transplantation, administration of Lantidra (minimum dosage: 5,000 islet equivalent/kg body weight) into the hepatic portal vein via percutaneous or transvenous transhepatic access, presents a safer and more minimally invasive surgical procedure. The efficacy and safety of Lantidra were examined in two core clinical studies, UIH-001 (Phase 1/2) and UIH-002 (Phase 3), at a single center (Pooled Population; n=30). Patients were screened to ensure an appropriate benefit-risk profile and received 1 to 3 Lantidra administrations. 19/30 patients (63%) met the composite efficacy endpoint (i.e., HbA1c ≤6.5% and absence of severe hypoglycemic events (SHEs) through 1 year after last transplant) and 20/30 (67%) were insulin independent at 1 year after last transplant. Importantly, improvements in glycemic control persisted. Two-thirds of patients assessed exhibited good glycemic control after 6 years. Lantidra demonstrated a safety profile consistent with known risks of the transplant procedure and concomitant medication use, particularly long-term use of immunosuppressants. The benefits of Lantidra outweigh the risks in T1D patients who have failed state-of-the-art insulin therapy. Lantidra fills a significant medical need, is effective at restoring good glycemic control in patients, and improves patient quality of life.

Disclosure

P. Rios: Employee; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc. Board Member; CellTrans, Inc. J.J. McGarrigle: Employee; CellTrans Inc. Stock/Shareholder; CellTrans Inc. Board Member; CellTrans Inc. G. LaMonica: Employee; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc. Y. Li: Other Relationship; Moderna, Inc. Employee; Cytel Inc. J. Cook: Employee; CellTrans Inc. Stock/Shareholder; CellTrans Inc. I. Joshi: Employee; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc. S. Ghani: Employee; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc. D. Cook: Employee; CellTrans Inc. Stock/Shareholder; CellTrans Inc. D. Lopez: Employee; CellTrans, Inc. H. Nasir: Employee; CellTrans. Y. Wang: Board Member; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc. J. Oberholzer: Board Member; CellTrans, Inc. Stock/Shareholder; CellTrans, Inc.
357-OR: Association between Continuous Glucose Monitoring and Diabetes-Related Complications in Children with Type 1 Diabetes—Nationwide Cohort Study
Authors: YOON KIM JI , KIM SEOHYUN , CHO SOHYUN , OH ROSA , HYEON KIM JAE
Published: June 2024

Introduction & Objective: This study aimed to investigate the effect of continuous glucose monitoring (CGM) on diabetes-related complications in children with type 1 diabetes.

Methods: From the Korean Nationwide Cohort (2016-2022), we included children (aged <19 years) with type 1 diabetes managed by intensive insulin therapy. The primary outcome included severe hypoglycemia and diabetic ketoacidosis (DKA). Adjusted hazard ratios (HRs) for primary outcomes were compared between CGM users and non-users by using Cox proportional hazard regression models. Additionally, among CGM users, the events of severe hypoglycemia and DKA were compared before and after CGM use by paired t-test.

Results: A total of 3,765 children (2,313 CGM users and 1,452 non-users) were included. During the follow-up period, CGM users showed a lower risk of severe hypoglycemia (adjusted HR: 0.48, 95% confidence interval (CI): 0.29-0.79) and DKA (adjusted HR: 0.44, 95% confidence interval (CI): 0.35-0.56). Among CGM users, the events of severe hypoglycemia and DKA significantly reduced after CGM use (p<0.001 for both).

Conclusion: In this nationwide cohort study, the use of CGM reduced the risk of severe hypoglycemia and DKA in children with type 1 diabetes receiving intensive insulin therapy.

Disclosure

J. Kim: None. S. Kim: None. S. Cho: None. R. Oh: None. J. Kim: None.
359-OR: CGM in Primary Care—Practice Characteristics and Choice of CGM Implementation Strategy in PREPARE 4 CGM
Authors: OSER SEAN , WIGGINS KIMBERLY T. , HALL TRISTEN , MIRIAM DICKINSON L. , CRISPE KRISTIN , DICKINSON PERRY , OSER TAMARA
Published: June 2024

Introduction & Objective: Most diabetes care occurs in primary care (PC). Continuous glucose monitoring (CGM) is associated with clinical and psychosocial benefits. While CGM uptake in PC is rising, understanding models to support CGM use in diverse PC practices is needed. The PREPARE 4 CGM study evaluates strategies to implement CGM in PC. We compared characteristics among practices choosing a practice-led, self-paced CGM implementation plan or referral to a virtual CGM implementation service.

Methods: Colorado PC practices interested in implementing CGM were recruited and chose to use the American Academy of Family Physicians CGM implementation modules or refer patients to a virtual CGM initiation and education service with dietitian, pharmacist, diabetes care and education specialist (DCES), and physician. Baseline practice characteristics (staffing, specialty, size, payer mix, etc) were compared across study arms using descriptive statistics (frequencies, means, SDs), chi-square tests, Fisher’s exact tests and independent two sample t-tests, using SAS 9.4 (Cary NC). Associations were considered significant at p<0.05.

Results: Of 76 practices, 46 chose self-paced implementation, 16 of which (35%) had a DCES; 30 chose the virtual service, none (0%) of which had a DCES, X2(2, N=62)=11.05, p <.001. Besides having a DCES, no differences in 50 other practice characteristics were seen between groups.

Conclusion: PC practices were eager to implement CGM. While other practice characteristics were not associated with implementation strategy choice, having a DCES was highly associated: all practices with a DCES chose to implement CGM on their own. DCESs may have potential as technology champions in PC practices. Referral to virtual CGM implementation service allowed access to a DCES and multidisciplinary team for practices without them. As many practices without a DCES also chose to implement CGM on their own, multiple models may be necessary to foster CGM implementation in PC.

Disclosure

S. Oser: Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Research Support; Abbott. Advisory Panel; Dexcom, Inc., Jaeb Center for Health Research. K.T. Wiggins: None. T. Hall: None. L. Dickinson: None. K. Crispe: None. P. Dickinson: None. T. Oser: Research Support; Abbott. Advisory Panel; Medscape. Consultant; Dexcom, Inc. Research Support; Insulet Corporation.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (G-2204-05191)
37-OR: Effectiveness of Continuous Glucose Monitoring on Short-Term In-Hospital Mortality among Frail Critically Ill Patients with COVID-19—An Exploratory, Prospective, Randomized, Open-Label, Parallel, Single-Center, Randomized Clinical Trial
Authors: WANG WEI , SHEN YUN
Published: June 2024

Objective: We aimed to investigate the effectiveness of CGM on intensive care unit (ICU) related outcomes among frail and critically ill patients with confirmed COVID-19.

Research Design and Methods: This was an exploratory, prospective, randomized, open-label, parallel, single-center clinical trial. A total of 124 patients was finally analyzed. The primary outcome was 28-day in-ICU mortality. The secondary outcome included the length of ICU stay, the occurrence of hypoglycemia and severe hypoglycemia events.

Results: The mean age was 78.3±11.5 years old. The mean fasting glucose level at baseline was 8.12±1.54 mmol/L. The mean HbA1c level was 7.2±0.8%. The percentage of participants with diabetes was 30.6%. The corresponding hazard ratio of the primary outcome in the isCGM group when compared with the POCT group was 0.18 (95%CI 0.04-0.79). The average length of ICU stay was 10.0±7.57 days in the isCGM group and 14.0±6.86 days in the POCT group (P < 0.05). There were fewer events of both hypoglycemia and severe hypoglycemia observed in the isCGM group compared to POCT group.

Conclusions: We found a significant clinical benefit from the use of CGM among frail and critically ill patients with COVID-19. These findings support the use of CGM in ICU and might help with the extension of application in various in-hospital settings.

Disclosure

W. Wang: None. Y. Shen: None.
376-P: Novel Continuous Glucose Monitoring Marker, Shannon Entropy, Is Significantly Correlated with Incidence of Severe Hypoglycemia
Authors: ZHANG XIAOHUA D. , KUEI LIN YU , ZHANG RENA D. , FISHER SIMON J.
Published: June 2024

Introduction & Objective: Detailed analysis of continuous glucose monitoring (CGM) data may identify novel risk markers for severe hypoglycemia (SH).

Methods: Correlations between established and novel CGM features (Table 1) derived from 30-day CGM data and the number of self-reported SH events in the previous 6 months were investigated in 163 adults with type 1 diabetes (T1DM).

Results: The number of SH events were significantly positively correlated with SD (p=0.0360), Mean (p=0.0446), TAR1 (p=0.0482), MODD (p=0.0448), 24-hour CONGA (p=0.0492), and significantly negatively correlated with TIR (p=0.0296), but was not significantly correlated with TBR2, TBR1, TAR2, CV, MAG, GVP nor MAGE (Table 1). The strongest CGM correlation with severe hypoglycemia was Shannon entropy (p=0.0161), a measure of randomness/disorder in the CGM data.

Conclusion: Surprisingly, the number of severe hypoglycemic event did not correlate with time below range. However, the novel CGM analytic feature of Shannon entropy had the strongest correlation with the number of SH events. These findings suggest that incorporation of CGM-derived Shannon entropy determinations may have clinical utility to identify T1DM adults at high risk for severe hypoglycemia.

Disclosure

X.D. Zhang: None. Y. Lin: None. R.D. Zhang: None. S.J. Fisher: None.

Funding

National Institutes of Health (UL1TR001998); National Institutes of Health (U01DK135111); National Institutes of Health (P30 DK020579); National Institutes of Health (OT2HL161847)
384-P: Comparative Efficacy of Irbesartan and Sotagliflozin in a Nonhuman Primate (NHP) Model of Diabetic Kidney Disease
Authors: DE VILLA FLORDELIZA P. , PEREZ ROSARIO M. , HUA ZHU Z. , YANG LICHUAN
Published: June 2024

Introduction and Objective: Renin-angiotensin system (RAS) inhibition has become the standard of care but new agents have emerged in the treatment of diabetic kidney disease (DKD) and its complications. Thus, the efficacy of irbesartan (IB), a RAS inhibitor, and sotagliflozin (SG), a dual SGLT1/2 inhibitor, on renal functional markers was evaluated in the most relevant animal model that closely approximates the human DKD phenotype.

Methods:Male cynomolgus monkeys with DKD [fasting blood glucose 281±82 mg/dL; 24h urine albumin creatinine ratio (UACR) 589±340 mg/g; glomerular filtration rate (GFR) 49±20 mL/min/1.73m2] from the high-fat diet NHP colony were selected for the study. Animals were dosed daily by oral gavage for 4 weeks with either vehicle (VH, n=8), IB at 3 mg/kg (n=12), or SG (n=5) at weekly escalating doses of 10, 12 and 14 mg/kg. Serial UACR, GFR and blood pressure (BP) measurements were done.

Results:UACR reductions were recorded for both IB and SG groups compared to the VH. Percent changes (%) from baseline of UACR were higher with IB treatment (-34±31 >-3±50 >23±23%; IB>SG>VH) but minimal sustained reductions were noted at the end of the 4-week washout period with SG (-7±53 vs 22±42%; SG vs IB). Marked sustained improvement in GFR was recorded in the SG group (27±16>16±93>9±43 %; SG>IB>VH) at the end of the washout period. Decreases in systolic BP (SBP; -11±8 %) and mean arterial pressure (MAP; -2±14%) were noted with IB during dosing with return to baseline at the end of the washout period. Decreased SBP (-8±8%), diastolic BP (-9±14 %) and MAP (-9±10%) during dosing, which continued until the end of washout, were seen in the SG group.

Conclusion:Treatments with IB and SG resulted in improvements in albuminuria and GFR with BP reductions. Sustained effects in renal function were noted with SG implying enhanced renoprotection with SGLT1/2 inhibition in this NHP model which is considered a vital translational model for testing novel interventions for DKD.

Disclosure

F.P. De Villa: None. R.M. Perez: None. Z.Z. Hua: None. L. Yang: None.
39-OR: Real-Time Continuous Glucose Monitoring–Guided Glucose Management in Hospitalized Patients with Diabetes Receiving Short-Term Continuous Subcutaneous Insulin Infusion—A Randomized Clinical Trial
Authors: WANG YAXIN , LU JINGYI , WANG MING , NI JIAYING , LU WEI , ZHU WEI , BAO YUQIAN , ZHOU JIAN
Published: June 2024

Background: The use of rtCGM remains largely investigational in the hospital setting. The current study aimed to evaluate the effect of rtCGM in inpatients with diabetes treated with short-term continuous subcutaneous insulin infusion (CSII).

Methods: In endocrinology wards located in a tertiary hospital, we assigned 475 adults with type 1 and type 2 diabetes requiring short-term CSII during hospitalization, to receive either rtCGM program (Figure 1) (n=237) or point-of-care (POC) standard of care with blinded CGM (n=238). Primary outcome was the difference in the percentage of time within the target glucose range of 3.9 to 10 mmol/L (TIR, %).

Results: The mean TIR was 71.1±15.8 % in the rtCGM group and 62.9±18.9 % in the POC group (P<0.001). The mean time above range >10mmol/L was significantly lower in rtCGM group than in POC group (28.3±15.8% vs. 36.6±19.0%, P<0.001), whereas there was no significant between-group difference in the time below range <3.9mmol/L (P=0.11). Moreover, the time to reach target glucose was significantly shorter in rtCGM group than in POC group (2.0 [1.0-4.0] vs. 4.0 [2.0-5.0] days, P<0.001).

Conclusion: In inpatients with diabetes receiving short-term CSII, rtCGM program resulted in better glucose control than POC standard of care, without increasing the risk of hypoglycemia.

Disclosure

Y. Wang: None. J. Lu: None. M. Wang: None. J. Ni: None. W. Lu: None. W. Zhu: None. Y. Bao: None. J. Zhou: None.
401-P: Fibrosis-4 Index Independently Predicts CKD Progression in Patients with Type 2 Diabetes and MAFLD
Authors: ZHANG CHENGHUI , SUYUAN WANG
Published: June 2024

Background: Fibrosis-4 (FIB-4) index is recommended by the American Diabetes Association Standard of Care 2024 for liver fibrosis screening in T2D. While the association between FIB-4 and increased cardiovascular disease has been established, its impact on the progression of chronic kidney disease (CKD) remains uncertain. This study aims to assess the influence of liver fibrosis, as measured by FIB-4, on CKD progression in patients with T2D and MAFLD.

Methods: The prospective cohort study enrolled 244 patients with both T2D and MAFLD. At baseline, FIB-4 was calculated based on several laboratory tests (AST/ALT/Platelets). The primary outcome was the progression of CKD, defined as a change of at least one CKD stage or incidence of macroalbuminuria or new-onset end-stage renal disease.

Results: The baseline characteristics are presented in Table 1. Over a median follow-up period of 2.1 years, 31 (12.7%) patients developed CKD progression. In multivariable Cox model, each unit increase in FIB-4 was associated with a 1.72-fold higher risk (95% CI:1.09-2.71; P=0.019) of CKD progression. Furthermore, compared with the patients in tertile 1, the adjusted-HR of CKD progression was 3.14 (95% CI: 0.80-12.25, P=0.100) and 4.90 (95% CI: 1.34-17.96, P=0.017) for those in tertile 2 and tertile 3, respectively.

Conclusion: In this cohort study of patients with T2D and MAFLD, FIB-4 was found to be an independent predictor of CKD.

Disclosure

C. Zhang: None. W. Suyuan: None.

Funding

Science and Technology Project of Tibet Autonomous Region (XZ202201ZR0037G)
417-P: Diabetic Foot Ulcer Amputation Increases the Risk of Severe Renal and Retinal Microvascular Complications—A Korean National Health Information Database Study
Authors: HYUN SONG NA , KIM BONGSEONG , JANG JINSUN , YANG HYEWON , SON HEEJUN , SEUNG JUNG HYE , MIN CHO YOUNG , SOO PARK KYONG , HAN KYUNGDO , HEON KWAK SOO
Published: June 2024

Diabetic foot ulcer (DFU) and subsequent amputation represents significant health burden associated with diabetes. It is widely recognized that individuals with diabetic end stage kidney disease (ESKD) and proliferative diabetic retinopathy (PDR) face an elevated risk of limb amputation, but vice versa remains unclear. This study aimed to investigate the incidence rate and quantify the risk of ESKD and PDR in people who experienced DFU amputation. Using the database from National Health Insurance Service in South Korea, we included people with diabetes who received national health screening from 2009 to 2012. DFU amputation was defined using International Classification of Diseases 10th revision codes (ICD-10). Incident cases of ESKD or PDR were defined as diagnoses occurring at least one year following DFU amputation, as determined by the ICD-10 codes. Cox proportional hazard regression analysis was used to estimate the risk of incident ESKD or PDR after DFU amputation adjusting for covariates. Among 1,447,438 individuals enrolled, 1,512 (0.10%) had received DFU amputation at baseline. The incidence rate (IR) of ESKD was significantly higher in people who received DFU amputation compared to those who did not (14.8 vs 1.6 per 1,000 person-years), and adjusted hazard ratio (HR) was 2.46 (95% CI 2.08-2.91). Similar result was observed for PDR; IR was 24.7 vs 6.5 per 1,000 person-years and adjusted HR was 2.08 (95% CI 1.82-2.38). When we performed subgroup analysis based on major vs minor amputation, subjects who received major amputations had higher risk for ESKD (HR 3.13, 95% CI 2.39-4.11) and PDR (HR 2.39, 95% CI 1.87-3.07) compared with subjects who received minor amputations (ESKD: HR 2.17, 95% CI 1.75-2.69; PDR: HR 1.97, 95% CI 1.68-2.31). In summary, using a national health information database, we found that people who received DFU amputation have significantly increased risk of microvascular complications of ESKD or PDR.

Disclosure

N. Song: None. B. Kim: None. J. Jang: None. H. Yang: None. H. Son: None. H. Jung: Research Support; Novo Nordisk. Y. Cho: None. K. Park: None. K. Han: None. S. Kwak: Employee; SNUH Venture.
432-P: Retrospective Analysis of Serum Lactate Levels and Risk for Contrast-Induced Nephropathy in Type 2 Diabetes Patients after Emergent Coronary Angiography or Emergent Percutaneous Coronary Intervention by Presence or Absence of Metformin
Authors: KONO YASUYUKI , HARAGUCHI MIKIKO , CHOU SHENGPU
Published: June 2024

Biguanides (BGs) rarely cause lactic acidosis, but it is induced by contrast media inhibiting renal excretion of BGs. However, there are few reported data on clinical influence of BGs to serum lactate levels under the use of contrast media, and risk for contrast-induced nephropathy (CIN) under BGs use is unknown. We included type 2 diabetes patients who underwent emergent coronary angiography (eCAG) or emergent percutaneous coronary intervention (ePCI) in New Tokyo Hospital from Jan. 1, 2015, to Dec. 31, 2021. We omitted cases confirmed with conditions that contraindicate metformin (Met) previously and selected 529 cases with pre-exam laboratory value of serum creatinine (SCr), albumin, hemoglobin, HbA1c, B-Type Natriuretic Peptide (BNP) and C-reactive protein, and creatine kinase-MB (CK-MB) within 48 hours. We retrospectively evaluated serum lactate and risk factors for CIN in this cohort by Welch’s t-test. Within 3 hours, two cases started hemodialysis and serum lactate was measured in 241 cases. There was no significant difference in maximum serum lactate between 63 Met users and 178 non-Met users, though the average and median were higher in Met users. Next, we evaluated risk factors for CIN. Within 72 hours, five cases died and SCr was follow-upped in 485 cases. BNP (p<0.05), HbA1c (p<0.05), and maximum CK-MB (p<0.01) were significantly higher in 68 CIN cases than in 417 non-CIN cases, but Met use or amount showed no significant difference. However, in 129 Met users, multiple CAG or PCI was significantly more frequent in CIN cases than in non-CIN cases (p<0.05). In diabetes patients undergoing eCAG or ePCI, Met use does not affect serum lactate significantly, and BNP, HbA1c, and maximum CK-MB are correlated to CIN. Multiple CAG or PCI may be related to CIN in Met users, and a further study with larger population is needed to evaluate this possibility.

Disclosure

Y. Kono: None. M. Haraguchi: None. S. Chou: None.
435-P: Prediabetes and Cardiovascular Disease (CVD) Risk—Insights from a Large-Scale Japanese Cohort Investigating the Impact of Regular Hospital Visits
Authors: MURAI KOSHIRO , FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , KITAZAWA MASARU , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: June 2024

We examined associations between prediabetes and the incidence of CVD according to whether patients made regular clinic visits for hypertension (HT) and dyslipidemia (DL). Enrolled were 1,137,069 Japanese without a history of CVD or glucose abnormality. During a median follow-up of 5.4 y, 10,893 people developed CVD. Prescription of antihypertensive or cholesterol-lowering agents indicated instructions to make regular clinic visits for HT or DL. Of those without regular clinic visits, CVD risk increased stepwise with increasing HbA1c values from the cutoff between diabetes and prediabetes. Those with HbA1c 6.5-6.8 had a higher CVD risk than those with prediabetes (Table). Conversely, of those making regular clinic visits, the CVD risk was significantly higher in persons with HbA1c levels just below criteria for diabetes (6.2-6.4%) than with normal HbA1c (≤5.6%). However, CVD risk did not significantly increase in those with HbA1c only slightly above the criteria for diabetes (6.5-6.8%). By regular clinic visits for HT or DL, a diagnosis of incident diabetes is speculated to trigger a quick response by attending physicians resulting in a better cardiovascular outcome than in those not attending clinic. These results indicate the need for strategies directed toward patients with early diabetes who do not regularly attend clinics for other diseases.

Disclosure

K. Murai: None. K. Fujihara: None. M.H. Yamada: None. M. Yamamoto: None. Y. Matsubayashi: None. M. Kitazawa: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.
441-P: Visceral Fat–to–Subcutaneous Fat Ratio Is Associated with High Carotid Plaque Score in Individuals with Type 2 Diabetes
Authors: YEL SHIN JANG
Published: June 2024

Visceral fat is considered as a major risk factor for metabolic disease and cardiovascular disease. This study investigated whether visceral fat to subcutaneous fat ratio (VSR) was associated with high carotid plaque score (PS) in individuals with type 2 diabetes. A total of 1966 patients with type 2 diabetes was enrolled. Visceral fat and android fat were automatically assessed using a dual energy X-ray absorptiometry and subcutaneous fat (g) were calculated as follows: android fat (g) - visceral fat (g). Carotid PS was ranged from 0 to 12 and high PS was defined as ≥ 3. Patients with high PS were 841 (42.8%). They were more likely to be old and male and had higher systolic blood pressure (SBP), visceral fat, and VSR, but lower diastolic BP (DBP), HDL cholesterol, estimated glomerular filtration rate (eGFR), subcutaneous fat, and grip strength than those without high PS. Subjects in the highest sex-specific VSR tertile group were older and had higher SBP, waist circumference (WC), visceral fat, triglyceride, and PS, but lower DBP, subcutaneous fat, appendicular skeletal muscle mass (ASM)/BMI, grip strength, HDL cholesterol, and eGFR compared with those in the lowest group. The prevalence of high PS was progressively increased with increasing sex-specific VSR tertile (lowest vs. middle vs. highest = 28.1% vs. 42.2% vs. 57.9%, p < 0.001). The odds ratios (ORs) and 95% confidence intervals (CIs) for the presence of high PS after adjusted for age and sex, were 1.45 (1.12 - 1.87. p = 0.004) in the middle and 1.92 (1.48 - 2.49, p < 0.001) in the highest VSR tertile groups. The ORs and 95% CIs in the higher VSR groups were remained significant after further adjusted for WC, SBP, DBP, triglyceride, HDL cholesterol, eGFR, ASM/BMI, and grip strength (p < 0.01).

In conclusion, higher VSR was significantly associated with high PS in patients with type 2 diabetes, independent of multiple potential risk factors.

Disclosure

J. Shin: None.
454-P: Screening for Cardiovascular Abnormalities in Chinese patients with Early-Onset Type 2 Diabetes Combined with Cluster Classification
Authors: LIAN HONG , REN QIAN , LIU WEI , ZHANG RUI , ZOU XIANTONG , HAN XUEYAO , JI LINONG
Published: June 2024

Introduction: Patients with early-onset type 2 diabetes (EOD) have 1.6-fold increased risk of cardiovascular death. Our study intends to screen for early cardiovascular abnormalities in EOD patients, and distinguish the population with cardiovascular risk through cluster classification.

Method: A total of 400 newly diagnosed EOD patients come from the Early onset diabetes Prospective multicenter study from Mar.2021 to Nov.2023. Echocardiography and carotid ultrasound were performed within 3 months after diagnosis. K-means was used for cluster classification based on age, BMI, HbA1c, HOMA2-β, HOMA2-IR, and GAD antibodies.

Result: Patients with left atrial/ventricular enlargement had higher BMI (32.78±5.58 vs. 28.92±5.10 kg/m2, p<0.001), C-peptide (3.86[3.02,4.76] vs. 3.05[2.23,4.07] ng/ml, p<0.001), and fasting insulin level (19.85[15.11,33.29] vs. 14.23[9.03,23.29] uU/ml, p<0.001). After adjusting for gender and BMI, patients with higher fasting insulin levels had an increased risk of left atrial/ventricular enlargement (OR=2.238, 95% CI: 1.179-4.250).

Conclusion: A higher proportion of EOD patients were diagnosed with cardiovascular abnormalities, especially those with obesity and insulin resistance (MOD and SIRD subtype). Cluster classification can help accurately distinguish patients at higher risk of cardiovascular complications.

Disclosure

H. Lian: None. Q. Ren: None. W. Liu: None. R. Zhang: None. X. Zou: None. X. Han: None. L. Ji: None.

Funding

Beijing Science and Technology Committee Fund (Z201100005520012)
455-P: The Triglyceride–Glucose Index and Type 2 Diabetes are Mutually Independent Predictors of Major Cardiovascular Events in Patients with Established Cardiovascular Disease
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established cardiovascular disease is unclear and is addressed in the present study. We enrolled 1790 consecutive patients, 1481 with angiographically proven CAD and 309 with sonographically proven PAD. Prospectively, MACE were recorded over a mean follow-up period of 10.7±5.0 years. At baseline, the TyG index was significantly higher in patients with T2DM (n=586) than in nondiabetic subjects (9.2±0.7 vs. 8.7±0.5; p<0.001). During follow-up, 916 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in nondiabetic subjects (60.2 vs. 47.7%; p<0.001). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.21 [1.12-1.30], p<0.001); HRs in patients without T2DM and in diabetic subjects were 1.08 [0.95-1.25], p=0.272 and 1.16 [1.03-1.31], p=0.013, respectively, with no evidence of an interaction between TyG and T2DM (p=0.093). With T2DM additionally entered into the regression model, TyG in the total study population predicted cardiovascular events independently from the presence of T2DM (HR 1.12 [1.03-1.23], p=0.008), while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.42 [1.19-1.67]; p<0.001). From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with CAD.

Disclosure

T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
460-P: Dual Role of Factor XI in Mortality and Diabetes—Insights from the Ludwigshafen Risk and Cardiovascular Health Study
Authors: PRYSTUPA KATSIARYNA , HENI MARTIN , HÖRBER SEBASTIAN , PETER ANDREAS , HELLSTERN PETER , KELM MALTE , YAMAZAKI HAJIME , RODEN MICHAEL , WAGNER ROBERT
Published: June 2024

Introduction & Objective: We investigated the effect of FXI on mortality in a cohort at increased risk for cardiac death, with a specific focus on risk-modification in case of type 2 diabetes (T2D) or current heart failure.

Methods: The prospective LURIC study recruited 3063 persons undergoing coronary diagnostics. Mortality risk was assessed using Cox proportional hazards models employing restricted cubic splines adjusted for age, sex, BMI and coronary artery disease, with interaction terms between FXI activity and T2D status as well as between FXI activity and brain natriuretic peptide (NTproBNP).

Results: In the unadjusted model, FXI activity demonstrated a U-shaped association with mortality risk (p=0.025): It was protective between 89-139%, but the risk increased at levels outside this range. A significant interaction of FXI activity with T2D (p=0.036) revealed that higher FXI activity was linked to reduced mortality in people without diabetes. However, this relation was inverted in participants with T2D (Fig. 1). NTproBNP was a further significant modifier of the relationship between FXI activity and mortality (p=0.0085).

Conclusion: T2D and NTproBNP significantly alter FXI activity's effect on mortality, underscoring a multifaceted interplay. Upcoming FXI-targeted therapies should be carefully evaluated in persons with diabetes with regards to their efficacy and safety.

Disclosure

K. Prystupa: None. M. Heni: Research Support; Boehringer-Ingelheim. Advisory Panel; Amryt Pharma Plc. Speaker's Bureau; Amryt Pharma Plc. Advisory Panel; Boehringer-Ingelheim, Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. S. Hörber: None. A. Peter: None. P. Hellstern: None. M. Kelm: Research Support; Edwards Lifesciences Coroporation, Microvision Medical, B.Braun, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC). Other Relationship; Bayer Inc., Abiomed. Board Member; ESC-European Society of Cardiology, DGIM-Deutsche Geselleschaft für Innere Medizin, DSHF-Deutsche Stiftung für Herzforschung, DGK-Deutsche Gesellschaft für Kardiologie. Other Relationship; Kel Con GmbH, diaplan. H. Yamazaki: Other Relationship; AstraZeneca, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Kyorin Pharmaceutical Co. Ltd, Takeda Pharmaceutical Company Limited, Takeda Pharmaceutical Company Limited, Magmitt Pharmaceutical Co. 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. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk.
465-P: Distribution of Remnant Cholesterol in Patients with Type 2 Diabetes and in Nondiabetic Patients with Established Cardiovascular Disease
Authors: DREXEL HEINZ , PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , SAELY CHRISTOPH H.
Published: June 2024

High remnant cholesterol is associated with the metabolic syndrome and with type 2 diabetes (T2DM) and has attracted much interest as a cardiovascular risk factor. However, its distribution in T2DM patients with established cardiovascular disease is not clear. This issue is addressed in the present study. We obtained remnant cholesterol in a large series of patients with established cardiovascular disease (1481 patients with angiographically diagnosed CAD and 323 patients with sonographically diagnosed PAD). From our patients, 592 had T2DM and 1210 did not have diabetes. Remnant cholesterol was significantly higher in T2DM patients than in nondiabetic patients (p<0.001), with median values [interquartile ranges] of 23 [9-38] mg/dl vs. 16 [5-32] mg/dl. The distribution of remnant cholesterol in T2DM patients and in those without diabetes is shown in the histograms in figure 1. Both in T2DM patients and in nondiabetic patients the distribution was markedly right-skewed and deviated significantly (p <0.001, by Kolmogrorov-Smirnov tests) from normal distribution. We conclude that remnant cholesterol in patients with established CAD is higher in patients with T2DM than in nondiabetic patients and both among T2DM patients and among those without diabetes is distributed in a markedly right-skewed manner.

Disclosure

H. Drexel: None. T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. C.H. Saely: None.
469-P: Both LDL Cholesterol and LDL Particles Associated with MACE in Tibetan Patients with Type 2 Diabetes
Authors: ZHANG CHENGHUI , SUYUAN WANG , LI MINGXIA
Published: June 2024

Background: LDL-C remains the primary treatment target for reducing major cardiovascular events (MACE) in patients with T2D. Our previous study revealed T2D patients residing in the Tibet Plateau exhibited elevated levels of LDL-C, LDL-particle number (LDL-P), but not small density LDL particles compared to those living in lowland areas. Whether the LDL-P is an independent predictor of MACE in Tibetan patients with T2D is unclear and is addressed in this study.

Methods: We conducted a perspective cohort study involving 165 patients, including 17 patients with established cardiovascular disease (13 of whom had angiographically confirmed stable coronary heart disease and 4 of whom had experienced stroke). Their demographic information, clinical feature, and standard lipid concentrations were collected and evaluated. LDL-P was measured by Nuclear magnetic resonance (NMR) spectroscopy. The primary outcome was MACE, including death from cardiovascular cause, non-fatal stroke, and non-fatal myocardial infarction. Cox proportional hazard models were utilized to examine the association between LDL-C and LDL-P with MACE.

Results: Over a median follow-up period of 26 months, 18 patients suffered MACE. The multivariate adjusted Cox regression model revealed a significant association between both LDL-C and LDL-P with MACE (Table 1).

Conclusion: Both LDL-C and LDL-P associated with MACE in Tibetan patients with T2D.

Disclosure

C. Zhang: None. W. Suyuan: None. M. Li: None.

Funding

Sichuan Medical Association (S21056)
47-OR: OPA1 Reprograms Macrophage Metabolism to Enforce Tolerance of Inflammation in Obesity
Authors: WANG DAIXI , HU CHENG , YAN JING
Published: June 2024

Introduction & Objective: Adipose tissue macrophages (ATMs) are key players orchestrating metabolic homeostasis through regulating metabolic inflammation. Mitochondrial dynamics and metabolic remodeling are pivotal for the function of macrophages. The aim of our study is to explore the role of the macrophage mitochondrial fusion protein, optic atrophy 1 (OPA1) in metabolic disorders and elucidate the underlying mechanisms.

Methods: We generate myeloid cell-specific OPA1 knockout and transgenic mice, subject them to a NCD or HFD to evaluate metabolic and inflammatory phenotypes. By using immunoblot analysis, flow cytometry, seahorse metabolic assays, metabolism assessment, combined with culturing bone marrow derived macrophages to reveal the molecular mechanisms of OPA1 in regulating metabolic reprogramming in macrophages.

Results: Myeloid-specific KO of OPA1 induces M2-like to M1-like macrophages shift in AT, thus promoting metabolic inflammation and exacerbating HFD-induced systemic insulin resistance, glucose dysregulation and liver steatosis in mice. In vitro studies show OPA1 loss impairs mitochondrial oxidative metabolism and inhibits JAK1/STAT6 pathway, resulting in decreased M2 polarization upon IL-4 stimulation. Mechanistically, OPA1 KO impairs the activity of itaconate transporter-Slc25a11 locating in the inner membrane of mitochondrial, leading to itaconate accumulation within the mitochondrial to suppress JAK1/STAT6. Further, mice with transgenic overexpression of OPA1 exhibit improved inflammation and metabolic homeostasis.

Conclusion: We reveal a novel role of OPA1 as a positive regulator of M2 macrophages polarization by governing metabolic reprogramming. Targeting macrophage OPA1 could represent a therapeutic target for AT inflammation and metabolic diseases.

Disclosure

D. Wang: None. C. Hu: None. J. Yan: None.

Funding

the National Science Foundation of China (82370879); Shanghai Rising-Star Program (23QA1407400)