bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-PUB: Prevalence and Associated Factors of Diabetic Retinopathy among Type 2 Diabetes in Beijing, China—A Cross-Sectional Study
Authors: WEI TIAN , ZHANG LIN , ZHU XIAO-RONG 
Published: June 2024

Objective: Diabetic retinopathy (DR) is the main cause of blindness in diabetic patients. The worldwide prevalence of Diabetic Retinopathy was recently estimated to be 34.6%. However, the prevalence and contributing factors of diabetic retinopathy remains controversial in the study areas. The aim of this study was to assess the prevalence of diabetic retinopathy and associated factor among type 2 diabetic patients in Beijing, China.
Methods: Cross-sectional study of all type 2 DM patients who attended diabetic eye screeningin Dongcheng District of Beijing from November 2022 to July 2023. A total of 2151 diabetes successfully completed ophthalmological examinations. The risk factors of DR were evaluated by OR value and 95% confidence interval after Binary logistic regression was used to adjust age and sex. Using SPSS22.0 software (IBM, Armonk, NY, USA) for statistical analysis.
Results: There were 129 DR in patients with diabetes mellitus, the prevalence of DR is 6.0% in type 2 diabetes. To analyze the risk factors of retinopathy after adjusting the age and sex in the peoples with diabetes. Multivariate regression analysis showed that duration of diabetes (8years, OR=1.54, 95%CI:, 1.13-2.12, P&lt;0.01), body mass index (BMI≥24kg/m2, OR=1.78, 95%CI:, 1.31-2.78, P=0.039), systolic blood pressure (per10mmHg, OR=1.13, 95%CI: increased; 1.03-1.24, P=0.012), Glycated hemoglobin ( OR=1.22, 95%CI:, 1.15-1.29, P&lt;0.001) were independent risk factors of DR.
Conclusions: The prevalence of diabetic retinopathy in type 2 diabetes is 6.0%, which is significantly lower than that of most studies abroad and in China. The risk factors for diabetic retinopathy in type 2 diabetic people are the duration ofdiabetes, systolic pressure, body mass index and Glycated hemoglobin.These risk factors should be controlled for the prevention of complications in patients with type 2 diabetes.

Disclosure
T. Wei: None. L. Zhang: None. X. Zhu: None.

Funding
Beijing Municipal Science & Technology Commission(Z221100007422065)
304-OR: The Obesity-Related Natriuretic Handicap Involves the Coordinated Regulation of Multiple Genes in Adipose Tissue to Blunt Natriuretic Peptide Signaling
Authors: CEDDIA RYAN P. , BRITTAIN EVAN , MASHAYEKHI MONA , HUANG SHI , JONES RACHEL , PALACIOS JULIA , REYNOLDS CASSANDRA F. , MAMBUNGU CINDY , ALP IKIZLER T. , WANG THOMAS , COLLINS SHEILA , GUPTA DEEPAK , BACHMANN KATHERINE N. 
Published: June 2024

Introduction & Objective: Obese individuals may experience a relative deficiency of natriuretic peptides (NP); this “NP handicap” may contribute to increased risks of hypertension, glucose intolerance, and fat accumulation in obesity. The pathogenesis of the NP handicap is not entirely known; elevated expression of the NP clearance receptor (NPRC) may contribute. We employ a comprehensive evaluation of the mechanisms underlying the NP handicap by measuring adipose gene expression of all 3 NP receptors, the peptidase neprilysin, and all cGMP degrading phosphodiesterases (PDE).
Methods: In a prospective study, we recruited 199 lean and obese adults (n = 55 lean, 144 obese; 56% female). We conducted biopsies of subcutaneous adipose tissue to measure gene expression and also measured circulating NP levels.
Results: Higher BMI was associated with lower circulating pro-Atrial NP and adipocyte gene expression of NPRA. Higher BMI was associated with higher adipose gene expression of proteins that degrade circulating NPs (NPRC, neprilysin) and blunt intracellular NP-evoked cGMP signaling (PDE 1A, 1C, 2A, 5A, 9A, 10A).
Conclusion: The obesity-related NP handicap is not only caused by upregulation of NPRC but appears to be a coordinated regulation of multiple genes in adipose tissue that work in concert to reduce NP signaling events.

Disclosure
R.P. Ceddia: None. E. Brittain: None. M. Mashayekhi: None. S. Huang: None. R. Jones: None. J. Palacios: None. C.F. Reynolds: None. C. Mambungu: None. T. Ikizler: None. T. Wang: None. S. Collins: None. D. Gupta: None. K.N. Bachmann: Employee; Amgen Inc. Stock/Shareholder; Medtronic, Pfizer Inc.

Funding
National Institutes of Health (HL145293, T32DK007061, UL1TR002243, KL2TR002245, DK020593, P30AI110527), U.S. Department of Veterans Affairs Clinical Sciences Research and Development (CSR&D) Program (IK2 CX001678), American Heart Association (17SFRN33520017), Vanderbilt Faculty Research Scholars, Vanderbilt Edge for Scholars Research Recovery fund
310-OR: Bacteremia and Endocarditis Complicating Moderate and Severe Diabetic Foot Infections
Authors: REYES MARIO C. , TARRICONE ARTHUR , PETERS EDGAR J. , ROGERS LEE C. , LAVERY LAWRENCE A. 
Published: June 2024

Introduction & Objective: There are few published studies concerning blood stream infections (BSI) in diabetic foot infections (DFI). Our objective was to evaluate the incidence and risk factors for BSI and endocarditis in diabetic patients admitted to the hospital with moderate and severe DFI. Our secondary aim was to evaluate the correlation of blood cultures and intraoperative wound cultures.
Methodology: This was a meta-analysis with pooled patient level data from 3 RTCs. Moderate and severe infection was based on criteria of the International Working Group on the Diabetic Foot classification. BSI was defined as a positive blood culture upon admission. Endocarditis was diagnosed by echocardiogram. We compared isolates from blood cultures and intraoperative wound cultures. Concordance was defined as any single pathogen isolated in wound cultures also isolated from blood cultures. We used χ2 and t-test for comparison of clinical events, with alpha of &lt;0.05.
Results: We evaluated 227 patients with blood cultures; (n=45) 19.8% had BSI. One (2.2%) patient had endocarditis. The concordance of wound cultures and blood culture pathogens was 66.7%. Polymicrobial infections were significantly more common in DFI vs BSI (48.7% vs 11.1%, p=&lt;0.001)
Conclusion: The incidence of BSI in people with DFI is very high (19.8%). There is a high concordance of BSI and DFI bacterial pathogens.

Disclosure
M.C. Reyes: None. A. Tarricone: None. E.J. Peters: None. L.C. Rogers: None. L.A. Lavery: None.
340-OR: Transcriptional Activation in Beta-Cells during ER Stress Linking iPLA2beta with NFkB
Authors: LEI XIAOYONG , KUMAR CHALLA ANIL , TUSING YING , NAKAYASU ERNESTO , MIRMIRA RAGHAVENDRA G. , CHALFANT CHARLES E. , RAMANADHAM SASANKA 
Published: June 2024

ER stress in β-cells has been reported to precede T1D development and we reported that the Ca2+-independent phospholipase A2β (iPLA2β) participates in ER stress-mediated β-cell apoptosis. Recently, we found that reduction in iPLA2β lowers T1D incidence. The iPLA2β hydrolyzes β-cell membrane glycerophospholipids to release arachidonic acid, which can be metabolized to inflammatory eicosanoids. Herein, we used insulinoma cells, human islets, spontaneously diabetes-prone NOD mice, and CRISPR-modified β-cells to address processes linking iPLA2β and ER stress. We find that cytokine-induced ER stress induces iPLA2β-mediated eicosanoid production, in association with NFκB activation and β-cell apoptosis. Surprisingly, inhibition or decreased iPLA2β expression also reduced NFκB activation at the transcriptional and protein levels. These observations were recapitulated in human and NOD.iPLA2β-/- islet β-cells and suggested potential regulatory links between iPLA2β and NFκB. To assess this at the molecular level, ChIP analyses were performed using MIN6 cells and not unexpectedly, an association between the transcription factor NFκB and PLA2G6, gene that encodes iPLA2β was observed. Intriguingly, ER stress also promoted association of iPLA2β with NF κ B and PLA2G6. Whereas inhibition of iPLA2β did not affect these associations, CRISPR-mediated reduction of iPLA2β significantly reduced both interactions. These observations suggest that iPLA2β protein itself, and not its lipid products, triggers transcriptional events to regulate its own production and that of apoptotic factors. Curiously, the iPLA2β protein is not recognized to have a DNA binding motif, therefore, suggesting that non-lipid co-factors likely link iPLA2β with target genes. Our findings identify a novel role for iPLA2β in modulating transcriptional events that are triggered during the development of ER stress, leading to β-cell death and T1D onset.

Disclosure
X. Lei: None. A. Challa: None. Y. Tusing: None. E. Nakayasu: None. R.G. Mirmira: None. C.E. Chalfant: None. S. Ramanadham: None.

Funding
NIH/NIDDK R01DK110292Beatson Foundation #2023-20UAB DRC P30 DK079626UAB Department of CDIBUAB Comprehensive Diabetes Center
353-OR: Chd3 Helicase Modulates Pancreatic ß-Cell Function in Absence of Chd4
Authors: KANOJIA SUKRATI , GEORGE RAJANI M. , OSMULSKI MEREDITH E. , DAVIDSON REBECCA K. , SANDOVAL KASSANDRA , HUTER KAYLA N. , SPAETH JASON 
Published: June 2024

Pdx1, an essential transcription factor during β-cell development, controls expression of genes required to maintain β-cell function through selective recruitment of transcriptional coregulators. We recently found that Chd4, a helicase within the Nucleosome Remodeling and Deacetylase (NuRD) complex, interacts with and modulates Pdx1 transcriptional activity in β-cells, in part by controlling chromatin accessibility. This investigation revealed that removing Chd4 from mature β-cells (Chd4Δβ) led to increased levels of Chd3, an alternate helicase subunit of the NuRD complex. We uncovered that Pdx1 and Chd3 interact in the mature β-cell and their interactions are increased in Chd4Δβ β-cells, leading us to question whether Chd3 alone influences β-cell function or compensates in the absence of Chd4. We therefore generated mouse models with tamoxifen-inducible, β-cell-specific deletions of Chd3 (Chd3Δβ) and Chd3/Chd4 (Chd3/4Δβ). Four weeks following Chd3 removal, Chd3Δβ mice showed no changes in glucose homeostasis, whereas Chd3/4Δβ mutants exhibited severe glucose intolerance. Chd3/4Δβ mutants displayed elevated ad libitum fed blood glucose levels, reduced β-cell mass, and insulin release in response to glucose was severely compromised, indicating a much more severe phenotype than Chd4Δβ mutants. Further investigation revealed an increase in β-cell apoptosis and aberrant expression of glucagon in lineage labeled Chd3/4-deficient β-cells. These data suggest that Chd3 compensates for loss of Chd4, and loss of both subunits leads to β-cell demise and loss of identity. Future efforts are focused on evaluating gene expression and chromatin accessibility changes in Chd3/4Δβ β-cells and the impact the diabetes milieu has on Pdx1:Chd3 interaction in β-cells of T2D mouse models and human donors with T2D.

Disclosure
S. Kanojia: Employee; Eli Lilly and Company. R.M. George: None. M.E. Osmulski: None. R.K. Davidson: Employee; Eli Lilly and Company. K. Sandoval: None. K.N. Huter: None. J. Spaeth: None.
43-OR: Endothelial Cell Regeneration by Secretome Secreted from P53-Silenced Bone Marrow–Derived BMSCs
Authors: RAO NANDULA SESHAGIRI , ARGAW ABEL , SEN SABYASACHI 
Published: June 2024

Diabetes is associated with impaired wound healing. Studies have demonstrated that endothelial progenitor cells (EPCs) and mature endothelial cells (EC) are susceptible to apoptosis in hyperglycemic environment and p53 gene silencing prevents cellular senescence and helps vascular regeneration. Previously we have shown that p53 silenced progenitor cell therapy helped tissue regeneration. Our goal is to test whether conditioned media obtained from p53 silenced human stem cells can also improve cellular regeneration.
Methods: Ad-human-P53 (TP53)-shRNA was used to silence P53 and Ad-scrambled-null-shRNA was used as control in bone marrow derived mesenchymal stromal cells. To collect conditioned mediaBM-MSCs were cultured in exosome free FBS media for 5 days, following transduction with Ad-p53sh or Ad-null, as the case may be. After transduction, cells were grown in media containing 2% exosome free FBS for only 48h and the collected supernatant was concentrated 10-fold to obtain the conditioned media (CM). Endothelial regeneration was tested using endothelial wound healing assay kit ( from Cell Biolabs # CBA-120-T).
Results: We compared CM obtained from null and p53sh in adipose and bone marrow derived mesenchymal stem cells on human endothelial cells in normal and high glucose conditions. Proliferation capacity of the p53sh CM was 2-3 fold more compared to null and non-transduced CM. The CM obtained from the untreated and null samples did not show increased proliferation in any of the cells tested. We are currently analyzing the secretome by mass spectroscopy.
Conclusion: P53 silencing appears to improve CM obtained from p53 silenced cells and may have therapeutic role in treating diabetes complications such as diabetic wound healing. [NSR1]is [NSR2]delete

Disclosure
S. Nandula: None. A. Argaw: None. S. Sen: None.
44-PUB: Electronic Health Record (EHR) Tools to Focus Care and Track Outcomes in a Community Health Worker Program (CHW) for Youth with Type 1 Diabetes
Authors: CRAVEN MEGHAN , TIMMONS KELLY D. , DEI-TUTU SELORM A. , BUTLER REBECCA , MARTINEZ AMELIA L. , JONES ADRINA , LYONS SARAH , SONABEND RONA Y. , DESALVO DANIEL 
Published: June 2024

As part of our ROCKET T1D initiative (Remote Outreach & Care for Kids’ Empowerment and Technology use in T1D), we launched a CHW program to address social drivers of health (SDOH) in youth with T1D at high risk for DKA. Eligible patients are identified using the Risk Index for DKA (RI-DKA) and the CHW serves as an extension of the care team with a focus on 5 goals: improving communication, accessing healthy food, navigating barriers to diabetes technology, applying for public benefits, facilitating transition to adult care.
To enable focused CHW care, we leveraged EHR-based “Episodes of Care” as structure for setting goals, identifying needs/resources, and tracking outreach tasks. Episodes are groups of linked program encounters with the ability to demonstrate outcomes from enrollment to completion via discrete data fields. The SDOH tool allows the CHW to monitor progress over 5 domains (food insecurity, housing, transportation, education, financial resources). “Goal Setting” allows the CHW to set goals, track progress, and share this information with the patient. “Outreach Tasks” on the CHW dashboard are used to view upcoming outreach for active participants.
Our CHW program went live in fall 2023 and outcomes will be tracked on our enterprise data warehouse, which integrates clinical, operational, and financial megadata produced from multiple sources across our system.

Disclosure
M. Craven: None. K.D. Timmons: None. S.A. Dei-Tutu: None. R. Butler: None. A.L. Martinez: None. A. Jones: None. S. Lyons: None. R.Y. Sonabend: None. D. DeSalvo: Advisory Panel; Insulet Corporation. Consultant; Dexcom, Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (2206-05307)
440-P: Influence of Sex on the Association between Vascular Endothelial Dysfunction and Plasma Leptin Levels in People with Type 2 Diabetes
Authors: MORIOKA TOMOAKI , NATSUKI YUKA , KAKUTANI YOSHINORI , YAMAZAKI YUKO , KURAJOH MASAFUMI , MORI KATSUHITO , SHOJI TETSUO , EMOTO MASANORI 
Published: June 2024

Evidence from basic studies indicates that leptin, a key hormone in the regulation of food intake and energy expenditure, induces endothelium-dependent vasorelaxation. It is well known that plasma leptin levels of women are higher than those of men, however, the influence of sex on the relationship between vascular function and leptin remains unclear. In this study, we investigated the influence of sex on the relationship between plasma leptin levels and vascular endothelial dysfunction in people with type 2 diabetes (T2D). We included 337 Japanese people (195 men and 142 women) with T2D in this study. We measured flow-mediated dilatation (FMD) of the brachial artery to evaluate vascular endothelial function. Compared to women, men had lower leptin levels (the medians 2.6 vs. 7.6 ng/mL, p &lt; 0.001) and lower FMD (the medians 5.6 vs. 6.4%, p = 0.044). Multivariate analysis revealed that plasma leptin levels in men were positively associated with FMD (β = 0.184, p = 0.034) independently of classical cardiovascular risk factors, such as age, BMI, HbA1c, eGFR, and serum phosphate levels. On the other hand, no association was found between serum leptin levels and FMD in women (β = 0.046, p = 0.662). Higher BMI and higher systolic blood pressure also showed an independent association with lower FMD in men, while only older age did in women. These data showed that there are sex differences in factors associated with FMD in people with T2D, and plasma leptin level is one of them. Considering the vasodilatory effect of leptin itself, this study suggests a functional relationship between low plasma leptin levels and vascular endothelial dysfunction in men with T2D.

Disclosure
T. Morioka: Research Support; Boehringer-Ingelheim, Eli Lilly and Company. Y. Natsuki: None. Y. Kakutani: None. Y. Yamazaki: None. M. Kurajoh: None. K. Mori: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, AstraZeneca, Lilly Diabetes, Kyowa Kirin Co., Ltd. T. Shoji: Speaker's Bureau; Kowa Company, Ltd., Bayer Inc., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd. M. Emoto: Research Support; Boehringer-Ingelheim, Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd. Research Support; Chugai Pharmaceutical.
443-P: Association of Stiffness Parameter ß with Urinary Albumin Excretion Rather Than eGFR in Type 2 Diabetes
Authors: NAKATANI SUSUMU , KAKUTANI YOSHINORI , MORIOKA TOMOAKI , YAMAZAKI YUKO , OCHI AKINOBU , MORI KATSUHITO , SHOJI TETSUO , EMOTO MASANORI 
Published: June 2024

Stiffness parameter β (stiffness β), a clinical estimate of arterial stiffness, increases with the progression of systemic atherosclerosis. Atherosclerosis is frequently and severely observed in patients with diabetic kidney disease (DKD) which is defined by decreased estimated glomerular filtration rate (eGFR) and/or elevated urinary albumin creatinine ratio (UACR). Both decreased eGFR and elevated UACR are known as risk factors of atherosclerosis. However, the contribution of each factor, eGFR or UACR, to arterial stiffness remains unclear. The present study aimed to investigate the association of eGFR or UACR with stiffness β in type 2 diabetes. Stiffness β was measured using ultrasonography at common carotid artery (CCA). The total 1,924 participants with type 2 diabetes including 58.8% of male were enrolled in this cross-sectional study. The mean age and HbA1c of all participants were 61.1 years and 8.6 %, respectively. The proportion of each CKD stage of eGFR (mL/min/1.73m2) and UACR (mg/g creatinine) were as follows: eGFR, 70.5% in G1/2 (≥ 60), 14.1% in G3a (45 - 60), 6.3% in G3b (30 - 45), and 9.0% in G4/5 (&lt; 30); UACR, 61.5% in A1 (&lt; 30), 20.3% in A2 (30 - 299), and 18.1% in A3 (≥ 300). Stiffness β (unitless) in G1/2, G3a, G3b, and G4/5 were 13.4 ± 5.8(SD), 15.0 ± 6.5, 16.1 ± 7.3, and 16.5 ± 7.4, respectively; and those in A1, A2, and A3 were 13.4 ± 5.9, 14.9 ± 6.1, and 15.8 ± 7.1, respectively. In univariate analysis, stiffness β was significantly correlated with both eGFR (r = −0.237, p &lt; 0.001) or UACR (r = 0.161, p &lt; 0.001). In multiple regression analyses, stiffness β was independently associated with UACR (β = 0.047, p = 0.043), but not with eGFR (β = −0.019, p = 0.439) after adjustment for classical risk factors.
In conclusion, stiffness β of CCA is associated with UACR, but not with eGFR, in patients with type 2 diabetes. Our findings suggest that stiffness β is more closely associated with UACR than eGFR in type 2 diabetes.

Disclosure
S. Nakatani: None. Y. Kakutani: None. T. Morioka: Research Support; Boehringer-Ingelheim, Eli Lilly and Company. Y. Yamazaki: None. A. Ochi: None. K. Mori: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, AstraZeneca, Lilly Diabetes, Kyowa Kirin Co., Ltd. T. Shoji: Speaker's Bureau; Kowa Company, Ltd., Bayer Inc., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd. M. Emoto: Research Support; Boehringer-Ingelheim, Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd. Research Support; Chugai Pharmaceutical.
481-P: Gastroparesis Symptoms among Type 1 Diabetes Patients—Prevalence and Associated Factors
Authors: ALAMOUDI REEM , ALLUGMANI EBTESAM B. , ALSUDAIRY NAJLAA M. , ALSHAMRANI ABDULLAH A. , ALMUTAIRI MARAM F. 
Published: June 2024

The development of gastroparesis-related symptoms in T1DM patients has major implications in the clinical course of the disease and physicians should be aware of the magnitude of the problem and its associated risks.
Objectives: To estimate the prevalence and identify predictors of gastroparesis in Saudi T1DM patients.
Methods: A cross-sectional study at King Abdulaziz Medical City Diabetes center, Jeddah, Saudi Arabia. All T1DM patients attending the endocrinology and diabetes clinics through Jan-Jun 2023 were approached. The Gastroparesis Cardinal Symptoms Index (GCSI) was utilized to diagnose gastroparesis.
Results: A total 113 T1DM patients were included. Age 12 - 54 (28.3 ±8.4) years. 63.7% were females, 26.5% overweight and 25.7% obese. Duration of diabetes 16.6 ±8 years, HbA1c% 8 ±1.5. Microvascular complications present in 24 (21.2%), 21.2% and 18.6% received statins and antihypertensives, and 12 (10.6%) were on metformin. Gastroparesis was present is 22 (19.5%). The most frequent reported symptoms were stomach fullness and feeling excessively full after meals (60.2%), followed by bloating (52.2%) and belly visibly larger (50.3%), whereas the lowest reported was vomiting (15.9%). Very severe form was reported in 9.7%. Multivariate logistic regression analysis revealed that females were at higher significant risk for developing gastroparesis compared to males (OR=4.36, 95% CI 1.15-16.56), p=0.031. Other studied factors (age, marital status, BMI, other chronic diseases, duration of diabetes, and microvascular complications) were not significantly associated with gastroparesis. HbA1c% was significantly higher in patients with gastroparesis compared to those without gastroparesis (8.9 ±1.9 versus 7.8 ±1.3), p=0.001. For every increase by one unit, the risk of developing gastroparesis increased by 59% (OR=1.59, 95% CI 1.16-2.19), p=0.004.
Conclusion: Gastroparesis symptoms are highly prevalent among Saudi T1DM patients and corollate with poor glycemic control.

Disclosure
R. Alamoudi: None. E.B. Allugmani: None. N.M. Alsudairy: None. A.A. Alshamrani: None. M.F. Almutairi: None.