bluuebunny/crossref_metadata_2025_split huggingface dataset:
1365-P: Key Characteristics and Predictive Ability for HbA1c Improvement—A Latent Class Analysis of 912 Patients
Authors: GAN YU , LENG LOW LIAN , HENG KWAN YU 
Published: June 2024

Introduction & Objectives: Type 2 Diabetes Mellitus (T2DM) strains healthcare. As mobile health (mHealth) interventions gain prominence in T2DM self-management, understanding the HbA1c response of diverse patient subgroups is crucial. This study aimed to classify T2DM patients into distinct latent classes and assess their predictive ability for 12-month HbA1c reduction.
Methods: Latent class analysis was applied to 912 T2DM patients using Fitbit-measured step tracker, aged ≥ 40 years old with HbA1c ≥ 7%. Exclusion criteria involved insulin treatment and cognitive impairment. Indicators comprised patients’ use of mHealth interventions, age, education, living arrangement, baseline levels of HbA1c, step count, and motivation (Patient Activation Measure). 12-Month HbA1c reduction was assessed with regression models.
Results: Within cohort (mean [SD] age 55.5 [7.6] years old; 55.9% male; 61.2% Chinese, 25.3% Malay, 9.8% Indian), Class 3 had the most significant HbA1c improvement, while lower baseline HbA1c and motivation suggest the contrary. Class 4, despite high baseline HbA1c, exhibited a significantly lower HbA1c improvement (Table 1).

Conclusion: Younger patients who are motivated and educated are most likely to be tech savvy to use and benefit from mHealth interventions. Patients with poorer control can make a more significant improvement in HbA1c through behavioural change.

Disclosure
Y. Gan: None. L. Low: None. Y. Kwan: None.

Funding
AI Singapore Programme (AISG-GC-2019-001-2A); Singapore Ministry of Health's National Medical Research Council (HCSAINV21jun-0004)
1370-P: The Association between Fatty Liver Disease Remission and Food Consumption among Chinese Adults—A Prospective Cohort Study
Authors: YI NING , DEHAO ZHANG , BI BO 
Published: June 2024

Background and Aims: Diet as a modifiable factor for remission of fatty liver disease (FLD) is rarely investigated. Therefore, this study investigated the association between FLD remission and 18 food items consumption.
Methods: This is a prospective open cohort study. Participants included 11,927 health examination participants from the Beijing MJ healthcare aged ≥ 18 years with diagnosis of FL by abdominal ultrasound examination at baseline. Semi-quantitative food frequency questionnaire was used to assess 18 food items intake during the follow-up. The percentage of energy from food items were divided by quartile. Hazard ratios (HRs) and 95% CIs of FLD remission across food items consumption were estimated with Cox proportional hazard regression models, adjusted for age, sex, total energy, and major confounding factors, and further stratified by non-alcoholic fatty liver disease (NAFLD).
Results: During a median follow-up of 1.3 years (interquartile range, 1.0-2.5), 4,541 individuals occurred FLD remission. The HRs (95%CI) for FLD remission comparing the highest with the lowest quartile of food items group were 1.19(1.09-1.30) for milk, 1.15(1.06-1.26) for eggs, 0.89(0.82-0.98) for fishery products, 0.89(0.82-0.98) for dark green vegetable, 1.19(1.09-1.31) for bread, 0.83(0.76-0.90) for sugar sweeten beverage, 0.82(0.74-0.91) for ultra processed food. Egg, fishery products, dark green vegetable, bread, and ultra processed food were all displayed linear dose-response relationships with FLD remission (P for non-linearity &gt;0.05). Similar results were found by NAFLD.
Conclusions: A high intakes from milk, egg, dark green vegetables, and bread, and a low intakes from fishery products, sugar-sweetened beverages, and ultra-processed food can independently improve fatty liver. These findings emphasize that patients can modify their dietary intake to alleviate FLD.

Disclosure
N. Yi: None. Z. Dehao: None. B. Bi: None.

Funding
Research Foundation for Advanced Talents of Hainan (820RC649)
1371-P: Examining Correlates of MyPlate Awareness and Use in Adults with Prediabetes in the United States
Authors: FOLIVI KEVIN , ANGUZU RONALD , WYCKOFF CARLIE , WALKER REBEKAH J. 
Published: June 2024

Objective: Given that 38% of adults in the United States have pre-diabetes, there is a demand for culturally tailored nutrition education as an effective intervention. The MyPlate system introduced by the USDA offers customizable portion control guidance. This study investigates correlates of MyPlate use among US adults aged 20 and older with pre-diabetes.
Methods: Weighted National Health and Nutrition Examination Survey data from 2017 to March 2020 were analyzed. Pre-diabetes was defined as individuals with HbA1c between 5.7% to 6.4% and having answered no if ever been told they had diabetes. Outcome was defined as indicating yes to awareness of MyPlate and no to use of MyPlate. Logistic regression was run with age, sex, race/ethnicity, insurance status, BMI, food insecurity, hypertension, and high LDL as possible correlates.
Results: Among 5,610 adults aged ≥20, prevalence of pre-diabetes was 21.2%. Among 2,359 adults who heard of MyPlate, 67.4% used it. Correlates of awareness of MyPlate but lack of use included age (60-80 years 0.52, 95%CI 0.29,0.93), female (0.37 and 95%CI 0.24,0.57), non-Hispanic Black (0.38 and 95%CI 0.19,0.75), and food-insecurity (2.10 and 95%CI 0.99,4.47).
Conclusions: Findings suggest tailoring MyPlate education to offer culturally relevant strategies for older adults, women, non-Hispanic black adults, and food-insecure individuals may be an effective strategy for improving outcomes for adults with pre-diabetes.

Disclosure
K. Folivi: None. R. Anguzu: None. C. Wyckoff: None. R.J. Walker: None.
1410-P: Natural History and Progression of Liver and Cardiac Health in Older Adults, a UK Biobank Study
Authors: DIAMOND CHARLIE , MCGONIGLE JOHN , JAYASWAL ARJUN , GATTU SUREKA , PANDYA PRASHANT , THOMAIDES-BREARS HELENA B. , DENNIS ANDREA 
Published: June 2024

Surveillance of cardiovascular and renal health is often prioritised in the care of diabetes with liver health often under recognised. We sought to determine how characteristics of the liver and heart progress over time in older adults from the general UK population, using quantitative magnetic resonance imaging. Clinical and imaging data were acquired on 2325 volunteers from the UK Biobank at two visits approximately 2.2 years apart between 2017 and 2021. Liver MRI scans were analysed using LiverMultiScan (for fat, iron content and disease activity, measured by iron-corrected T1, cT1). Paired cardiovascular magnetic resonance data for left ventricular ejection fraction (LVEF) was available on a subset of 709 volunteers. For groupwise statistical comparisons, Wilcoxon rank sum tests were applied for continuous variables and Fishers exact tests for categorical variables. At baseline, the 2325 volunteers were characterised by the following demographics: mean age 63 (SD 7) years, 48% male, mean BMI 26 (SD 4) kg/m2, 15% obese, 4.1% self-reported diabetic and 24% self-reported hypertensive. Elevated liver fat was common with a prevalence of 25%. Liver disease activity was rare in this cohort, mean liver cT1 was 694ms with only 3.4% abnormally high (≥800ms) and 2.9% with steatohepatitis. Mean liver iron levels were 1.24mg Fe/g (2% clinically high). Mean LVEF was 56% at baseline and abnormally low in 10%. At follow-up 2.2 years later, we observe no overall significant changes in prevalence of diabetes, BMI, liver fat, liver iron content or LVEF values. Overall, liver cT1 significantly increased by a mean of 5ms (SD 32) (p = &lt;0.001). Although significant, this increase is not clinically meaningful, except in 9% with increases above and 5% decreases below the repeatability coefficient. This longitudinal dataset provides evidence for the stability of quantitative liver (cT1, fat and iron) and cardiac (LVEF) MRI metrics in a low disease population of older adults, to power future studies.

Disclosure
C. Diamond: Employee; Perspectum Ltd. J. McGonigle: Employee; Perspectum Ltd. A. Jayaswal: Employee; Perspectum Ltd. Stock/Shareholder; Perspectum Ltd. S. Gattu: None. P. Pandya: Employee; Perspectum Ltd. H.B. Thomaides-Brears: Employee; Perspectum Ltd. Stock/Shareholder; Perspectum Ltd. A. Dennis: Employee; Perspectum Ltd.
1420-P: Global Burden and Trend of Type 2 DM in 38 OECD Countries from 1990–2019—A Benchmarking Systematic Analysis
Authors: MARKANDU KEETHANSHAN , DEKHNE ANUSHKA , ISLAM HAMZA , ISLAM RABIA , MADDINENI KAVYA , POTLURI GEETHIKA , PARISAPOGU ANUSHA , TEJA CHINTHAPALLI MRUNAL , DINESHBHAI DESAI HARDIK 
Published: June 2024

Introduction: Type 2 Diabetes Mellitus (T2DM) is a significant public health concern across the world, notably as the 8th leading cause of death after Colorectal cancer in OECD countries in 2019.
Method: Using the Global Burden of Disease approach, this study analyzes T2DM in terms of incidence, prevalence, mortality, and DALYs over 30 years (1990-2019) across 38 OECD countries, stratified by age, sex, year, and location.
Results: The study shows a significant increase in T2DM from 1990-2019: the annual percentage of change (APC) in prevalence of cases surged by 147%, deaths rose by 60%, and DALYs doubled. Notably, Latvia experienced the highest rise in T2DM-related deaths (347%), followed by the Republic of Korea (279%). The highest incidence rates were observed in Luxembourg (439%) and Ireland (411%). The data indicates a consistently higher burden of T2DM on males compared to females over the past three decades. Additionally, individuals under 70 years of age saw a 34% increase in T2DM-related deaths, whereas those aged 70 and above experienced a 74% rise from 1990 to 2019.
Conclusion: In 2019, T2DM accounted for 2.67% of deaths from all causes. The findings underscore the urgent need for targeted public health interventions, especially in lower-resource countries. Clinicians are advised to closely monitor the ongoing burden of T2DM and to implement preventive measures and surveillance strategies.

Disclosure
K. Markandu: None. A. Dekhne: None. H. Islam: None. R. Islam: None. K. Maddineni: None. G. Potluri: None. A. Parisapogu: None. M. Chinthapalli: None. H. Desai: None.
1426-P: Type 2 Diabetes Phenotypes and Their Association with Mortality in South Asians—Findings from the Center for Cardiometabolic Risk Reduction in South Asia (CARRS) Study
Authors: TIWARI PRADEEP K. , MOHAN ANJANA RANJIT , JAGANNATHAN RAM , KONDAL DIMPLE , DEEPA MOHAN , GUJRAL UNJALI , WALIA GAGANDEEP K. , RADHA VENKATESAN , PANDEY RAJESH , SENGUPTA SHANTANU , SUN YAN , ALI MOHAMMED K. , PRABHAKARAN DORAIRAJ , MOHAN VISWANATHAN , TANDON NIKHIL , VENKAT NARAYAN K M 
Published: June 2024

Background: Characterizing heterogeneity of type 2 diabetes (T2D) is essential for precision diabetes. We investigated phenotype clusters within T2D and their associations with mortality in South Asians.
Methods: In 2,639 individuals diagnosed with T2D from the CARRS cohort, we characterized T2D phenotypes by applying k-means clustering on age at diabetes diagnosis, BMI, HbA1c, HOMA-B, and HOMA-IR. All-cause mortality outcomes within these phenotypes were assessed over a median follow-up of 11-years using the Cox proportional hazard model.
Results: Three distinct phenotypes were identified: Mild Obesity-related Diabetes (MOD; 22.6%), characterized by high BMI but good HbA1c control; Mild Insulin Deficient Diabetes (MIDD; 54.5 %), observed in older individuals with lower BMI, lower HbA1c, and mild insulin deficiency; and Severe Insulin Deficient Diabetes (SIDD; 22.9 %) characterized by young age of onset of diabetes and severely impaired beta-cell function. Compared to individuals with normal glucose tolerance, SIDD exhibited the highest mortality rate followed by MIDD and MOD (Table).
Conclusion: Our data indicate that insulin deficiency phenotypes (MIDD and SIDD) are the primary drivers of T2D in South Asians and account for 82.5% of mortality.

Disclosure
P.K. Tiwari: None. R. Anjana: None. R. Jagannathan: None. D. Kondal: None. M. Deepa: None. U. Gujral: None. G.K. Walia: None. V. Radha: None. R. Pandey: None. S. Sengupta: None. Y. Sun: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. D. Prabhakaran: None. V. Mohan: None. N. Tandon: None. K. Narayan: None.

Funding
National Institutes of Health (P01HL154996)
1449-P: Identification of Type 1 Diabetes by an Electronic Health Records Algorithm from the CURE-CKD Registry
Authors: GREENBAUM CARLA , REYNOLDS CHRISTINA L. , JONES CAMI , KORNOWSKE LINDSEY , DARATHA KENN B. , ALICIC RADICA Z. , NEUMILLER JOSHUA J. , TUTTLE KATHERINE R. 
Published: June 2024

Introduction & Objective: Electronic health records (EHR) are a valuable source of real-world data for clinical research. Reliable methods are needed to identify type 1 diabetes (T1D) by EHR. The study aim was to develop an EHR algorithm for T1D using diagnosis codes and clinical characteristics validated by manual chart review.
Methods: Data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) Registry were used to identify persons ≥12 years of age with T1D by diagnosis codes, ketoacidosis encounters, insulin pump and short-acting insulin use during 2013-2022. Manual chart review was performed on a subset of 100 participants to verify selection criteria; 40 from “very likely” category, 40 from “likely” category, and 20 from “unlikely”.
Results: T1D cohorts (N=31,695) were divided into likelihood categories based on confirming criteria (Figure). The cohort was 48.5% female and 75.7% White race identity. Their mean±SD for age was 42±19 years with HbA1c 8.2±2.1% and BMI 27.5±6.3 kg/m2. Positive predictive values were 100% for very likely, 98% for likely, and 40% for unlikely categories.
Conclusions: T1D can be reliably identified by the CURE-CKD algorithm using clinical EHR data. Pending further validation, this algorithm can be used for T1D cohort selection in real-world studies of epidemiology, diagnosis, and treatment.

Disclosure
C. Greenbaum: Other Relationship; Sanofi, Takeda Pharmaceutical Company Limited, Bristol-Myers Squibb Company, Imcyse. C.L. Reynolds: None. C. Jones: None. L. Kornowske: None. K.B. Daratha: None. R.Z. Alicic: Advisory Panel; Bayer Inc., Boehringer-Ingelheim. Research Support; AstraZeneca, Bayer Inc., AstraZeneca, Novo Nordisk, Traveere Pharmaceuticals. J.J. Neumiller: Advisory Panel; Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Proteomics International. K.R. Tuttle: Consultant; Lilly Diabetes. Research Support; Boehringer-Ingelheim. Consultant; AstraZeneca. Research Support; Novo Nordisk, Bayer Inc., Traveere Pharmaceuticals. Consultant; Pfizer Inc.

Funding
CDC (75D301-21-P-12254)
1490-P: Diabetes Induces Impaired Fibrotic Response to Mesh Involving Macrophage Dysfunction
Authors: LIANG RUI 
Published: June 2024

Introduction: Women with diabetes have ~5-fold increased risk of mesh exposure into vaginal cavity following synthetic mesh augmentation in the surgical repair of pelvic floor disorders. To define the mechanism relevant to host fibrotic response, we studied the impact of diabetes on fibrillogenesis at mesh-tissue interface with a focus on the role of macrophages.
Methods: Diabetes was induced in Wistar rats using streptozotocin for 2 weeks. Rats w/wo diabetes underwent mesh implantation via sacrocolpopexy for 7- and 42-days (n=8 per time point per group). Fibrotic response (350μm adjacent to mesh), including thinner (G) vs. thicker (R) fibers and collagen density were quantified in Picrosirius Red images. TGF-β1 level in tissue extracts was measured using ELISA. Macrophage transcriptomics was sequenced following tissue dissociation and flow-sorting. CD68+αSMA+ cells were examined in tissue sections using immunofluorescence. CLC Genomics Workbench 22 (fold change&gt;2, FDR&lt;.05) and Mann-Whitney tests (p&lt;.05) were used for statistics.
Results: In nondiabetics, the fibrotic response progressed with an increase in collagen density (p=0.008), and a decrease in TGF-β1 (p=.007) over time. The R/G ratio was not changed (p=.45). In contrast, diabetics displayed a deregulated pattern with impaired formation of thicker R fibers (p=.009), resulting in increased G fibers (p=.007) and decreased R/G (p=.014) at 42- vs. 7- days, while the collagen density and TGF-β1 level were unchanged over time (p=.49, .75). Paradoxically, macrophage expression of αSMA (myofibroblast marker) and major collagens (I, III, VI and VI) was increased ~4-fold relative to those in the nondiabetics at 42 days (FDR&lt;.05). Cells with positively co-labeled CD68 (macrophage marker) and αSMA were identified at mesh-tissue interface.
Conclusions: Long-term diabetes negatively impacts host fibrotic response to mesh. The increase of macrophage-myofibroblast trandifferentiation in the process is yet to be elucidated.

Disclosure
R. Liang: None.

Funding
National Institutes of Health (R01HD108666)
1501-P: Four Loci, Four Fates—Differential Regulation of IRF5 Promoter in Prodiabetogenic Stress
Authors: AL MADHOUN ASHRAF , AREFANIAN HOSSEIN , KOCHUMON SHIHAB P. , AKHTER NADEEM , WILSON AJIT , ALBELOUSHI SHAIMA , ALRASHED FATEMA , BAHMAN FATEMAH , AL-MANSOUR NOURAH , ALZAID FAWAZ , ALMULLA FAHD , AHMAD RASHEED , SINDHU SARDAR T. 
Published: June 2024

Introduction: Interferon regulatory factor (IRF)-5 is a transcription factor sitting at the crossroads of diverse cell processes. Emerging evidence supports its upregulation in response to different stimuli, however, the associated molecular mechanisms remain elusive.
Methods: Four distinct IRF5 regulatory loci 1A, 1B, 1C, & 1D were individually cloned into Luciferase-based reporter vectors. RAW 264.7 macrophage cells were transfected with each of four reporter constructs and cells were exposed for 24h to stress stimuli including 100 µM palmitate (saturated FA), 100 µM oleate (unsaturated FA), 100 µM H2O2 (ROS inducer), 100 ng/mL TNF-α (inflammatory cytokine), 25 mM glucose (hyperglycemia), or 30 ng/mL IFN-γ (inflammatory cytokine). Luciferase activity was measured and normalized to Renilla luciferase activity. In additional experiments, co-transfections were performed using each promoter construct and expression vectors for E2F, NRF2, and STAT3 to investigate their potential roles. Statistical analysis was performed using two-way ANOVA.
Results: Luciferase assays revealed a differential response of the four IRF5 promoter loci. IRF5-1C exhibited the least significant regulation in mouse macrophages. Alternatively, 1A, 1B, and 1D displayed the increased reporter activities (300-fold compared to the control construct). Palmitate and H2O2 treatments triggered activation at all four promoter sites, while oleate stimulated only the 1D promoter region. Interestingly, TNF-α, hyperglycemia, and IFN-γ failed to induce IRF5 promoter activity at any of these loci. Co-transfections with transcription factor E2F stimulated luciferase activity at all four promoter loci, NRF2 stimulated activity at loci 1A, 1B, and 1D, and STAT3 stimulated activity at loci 1A and 1B.
Conclusion: Our findings demonstrate that the four IRF5 promoter loci exhibit distinct responses to stimuli that mimic the pro-diabetogenic stress via the mechanism involving specific transcriptional regulators.

Disclosure
A. Al Madhoun: None. H. Arefanian: None. S.P. Kochumon: None. N. Akhter: None. A. Wilson: None. S. Albeloushi: None. F. Alrashed: None. F. Bahman: None. N. Al-Mansour: None. F. Alzaid: None. F. Almulla: None. R. Ahmad: None. S.T. Sindhu: None.

Funding
Kuwait Foundation for the Advancement of Sciences (KFAS) (RA 2015-027)
1509-P: The Mesenchymal Stromal Cells in “Neo-islets,” Islet-Sized 3D Organoids Composed of MSCs and Islet Cells That Functionally Cure Type 1 Diabetes, Actively Preserve Normal ATP Levels and Viability of ICs In Vitro and In Vivo—Applicable to Islet and iPSC-Derived Therapies of Type 1 Diabetes Mellitus
Authors: GOOCH ANNA , WESTENFELDER CHRISTOF 
Published: June 2024

Allotransplants of pancreatic islets in patients with T1DM require their isolation from deceased donor pancreata. This process results in the ischemic loss of up to 50% of islets. Their intraportal administration leads to further islet death due to low oxygen pressure, the Instant Blood-Mediated Inflammatory Reaction and subsequent exposure to high concentrations of orally administered cytotoxic anti-rejection drugs. Despite the use of anti-rejection drugs, a significant percentage of transplanted islets lose their function over time and need to be replaced. The objective of the current study was to determine whether MSCs that are co-aggregated (1:1 ratio) with ICs in “Neo-Islets” protect IC viability by maintaining their ATP levels. This was tested by in vitro exposure x 24 hrs. of cultured human MSCs, ICs and “Neo-Islets” to 1% pO2. Not unexpectedly, at 24 hrs of hypoxia ATP levels of cultured human ICs (P2) fell from 78±10 to 40±2 pg/cell (p=0.02) and viability decreased to 50%, while ATP levels and viability of identically cultured MSCs remained normal, likely Pasteur effect mediated. Significantly, total ATP levels in freshly formed Neo-Islets remained normal during hypoxia and viability remained close to 99%. Several groups have now demonstrated that MSCs transfer mitochondria though nanotubes into hypoxically stressed neighboring cells, a process that enhances ATP levels and thereby improves their survival.
Conclusion: This ATP-mediated cytoprotective activity of MSCs, combined with their anti-apoptotic, immune-isolating, anti-inflammatory, angiogenic and other trophic actions are exploited in “Neo-islets”. The utility of this co-aggregation technology will be tested to determine whether it can significantly improve islet and novel iPSC-derived transplants that are used to treat patients with T1DM.

Disclosure
A. Gooch: Employee; SymbioCellTech, LLC. Board Member; SymbioCellTech, LLC. Stock/Shareholder; SymbioCellTech, LLC. C. Westenfelder: None.
1516-P: Epigenetic Changes in Insulin Signaling Genes and Cancer Pathway Genes with Remission of Prediabetes
Authors: STENTZ FRANKIE B. , AMMONS ANN 
Published: June 2024

Prediabetes or impaired glucose tolerance (IGT) is often seen in conjunction with obesity and both are associated with increased incidence of various diseases. The purpose of this study was to determine if epigenetic changes of DNA occur in patients that convert from prediabetic to normal glucose tolerance(NGT) by determining DNA methylation at baseline and at remission of prediabetes at 6 months (mo).
Methods: 24 obese adults with prediabetes were randomized to a High Protein (HP)(30% protein(P), 30% fat(F), 40% carbohydrates(C)) or High Carbohydrate (HC)(15%P, 30%F, 55%C) diet for 6 mo with all food provided. Oral Glucose Tolerance Test (OGTT) was performed at Baseline (BL) and 6 mo to determine IGT/NGT status. DNA was extracted from BL and 6 mo OGTT 0-minute blood samples. Specific site DNA methylation was determined.
Results: The HP diet group had 100%(12/12) conversion to NGT while the HC diet had 33%(4/12) conversion. Both diet groups had weight loss and improvement in insulin sensitivity determined by Matsuda Index [HP(BL 2.3 ± 0.3; 6 mo 6.5 ±1.1)], [HC(2.3±0.3; 6 mo 3.2±0.4)]. Changes in DNA methylation of numerous genes were observed from BL to 6 mo with remission of prediabetes and weight loss. Some of these genes with altered DNA methylation include the KEGG pathways of: insulin signaling(IS)(11 genes), cardiovascular disease(CV)(15 genes), inflammation(IF)(18 genes), metabolic pathways(MP)(32 genes), and cancer pathways(31 genes). Changes in DNA methylation of genes involved in IS, CV, MP, correlate with the improvements in IS, CV and IF in the subjects after 6 months on the diets. Of the cancer pathway genes and insulin signaling and inflammation genes 18 of the changes in DNA methylation of the genes were the same.
Conclusions: The HP diet was the most effective with respect to DNA methylation changes and clinical parameters. The DNA methylation changes of specific genes may be important for reduction of certain disease states and can be improved by diet and weight loss.

Disclosure
F.B. Stentz: None. A. Ammons: None.