bluuebunny/crossref_metadata_2025_split huggingface dataset:
1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset
Authors: RIPPA ALEXANDRA , DROTAR DENISE M. , POSGAI AMANDA , HULME MAIGAN A. , WASSERFALL CLIVE , KUSMARTSEVA IRINA , CAMPBELL-THOMPSON MARTHA , ATKINSON MARK A. 
Published: June 2024

Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet fluorescent microscopy (LSFM) to quantify CD8+ cells within islets and surrounding exocrine regions.
Methods: Pancreas samples from non-diabetic controls (ND, n = 4; age range 16-24 yr), non-diabetic GAD autoantibody-positive (GADA, n = 3; 18-24 yr), and recent-onset (duration &lt;2 yr) T1D subjects (n = 4; 3-26 yr) were fixed, stained for insulin (INS), glucagon (GCG) and CD8a, cleared and imaged using LSFM. A mean tissue volume of 4.3x108 µm3 per donor was analyzed using Imaris. We generated 3D surfaces (INS+ and GCG+ signals) and 3D spots (CD8a+ cells), with analysis of 516 total islets (201 ND, 162 GADA, 153 T1D). Endocrine pancreas infiltration was quantified using CD8a spots contacting and inside islet surfaces. To assess exocrine infiltration, CD8a spots outside of the islets were quantified. Fold change and mean ± SEM values were analyzed by one-way ANOVA with Tukey's post-test.
Results: T1D donors had significantly increased CD8a+ cells in exocrine (5.5-fold more than ND, 3.6-fold more than GADA, p&lt;0.05) and endocrine pancreas (13-fold more than ND, 12-fold more than GADA, p≤0.02). The percentage of islets containing at least one CD8a+ cell was also increased in T1D (64 ± 0.02%, p&lt;0.05) vs ND (28 ± 0.06%) and GADA (23 ± 0.08%). The maximum number of CD8a+ cells per islet was higher in T1D (133.5 ± 40.5, p≤0.02) vs ND (7.5 ± 2.3) and GADA (10 ± 2.3).
Conclusion: This 3D analysis of the human pancreas provides a comprehensive view of immune cell distribution in T1D, enabling quantification of infiltration throughout the exocrine and endocrine compartments. Such efforts will advance our ability to identify the pathogenic mechanisms underlying pancreatic inflammation in T1D.

Disclosure
A. Rippa: None. A. Posgai: None. M.A. Hulme: None. C. Wasserfall: None. I. Kusmartseva: None. M. Campbell-Thompson: None. M.A. Atkinson: None.
1961-LB: Evaluation of Two Behavioral Economic Interventions for Youth with Type 1 Diabetes—A Randomized Controlled Trial
Authors: TSAI SARAH , MCDONOUGH RYAN , PATTON SUSANA R. , DEWIT EMILY L. , SPARTZ BRITANEY , WILLIAMS DAVID D. , LOCKEE BRENT , CLEMENTS MARK A. 
Published: June 2024

Introduction & Objective: Mealtime insulin dosing behavior is critical to glycemic control in youth with type 1 diabetes (T1D). Behavioral Economic Incentives (BEI) have been shown to improve self-management behaviors. We report interim results of a randomized trial evaluating 2 forms of a BEI to improve mealtime insulin dosing in youth with T1D.
Methods: We recruited youth with T1D with current A1C &gt;7.2%, and/or predicted to have a 90-day rise in A1C of 0.3% via machine learning-based model. Subjects were randomized into 3 groups: COIN2DOSE (C2D) - uses positive financial incentives to promote mealtime insulin use, with weekly bonuses for sustained meal dosing; LOAN2DOSE (L2D) - uses a loss aversion approach to promote mealtime insulin use; or control. The potential financial compensation was equal for C2D and L2D over the 12-week intervention period.
Results: To date, 32 youth have enrolled and 24 have completed the study [mean age= 14.8±1.4 years, mean T1D duration= 7.1± 3.2 years, mean A1C=8.9±1.6%, 58% female, 9 C2D, 6 L2D, 9 control]. At baseline, there were no differences in A1C, time in range (TIR), or mealtime insulin use (BOLUS) by group. Mean BOLUS score showed a non-statistically significant increase from 0.93±0.93 to 1.3± 0.92 in C2D baseline to post-treatment, which was sustained at 6-months post-baseline (p=0.64). Mean BOLUS score increased from 1.1±0.1to 1.4±1.0 in L2D baseline to post-treatment but decreased to 0.86±0.15 at 6-months post-baseline (p=0.82). The control group BOLUS score increased from 1.3±1.0 to 1.4±0.9 at post-treatment and 1.5±0.78 at 6-months post-baseline (p=0.86). Across groups, there were no changes in TIR and A1C at post-treatment or 6-months post-baseline.
Conclusion: Preliminary results suggest that either positive financial incentives or loss aversion may be associated with short-term improvement in mealtime insulin use, but not A1C or TIR. We continue the trial to enable more testing of group differences and long-term impact.

Disclosure
S. Tsai: Stock/Shareholder; Dexcom, Inc. R. McDonough: Speaker's Bureau; Provention Bio, Inc. S.R. Patton: None. B. Spartz: None. D.D. Williams: None. B. Lockee: None. M.A. Clements: Research Support; Abbott. Consultant; Glooko, Inc. Research Support; Dexcom, Inc.

Funding
Helmsley Charitable Trust
1964-LB: Association between Fasting Venous Lactate Level and Development of Preeclampsia in Pregnant Individuals with Gestational Glucose Intolerance
Authors: PURVIS REBECCA , VAN NES JACLYN , ZITE NIKKI , REEDER CALLIE , MASTRONARDI ALICIA , OYEDEJI OLUWAFEMIFOLA , BROSKEY NICHOLAS T. , MAPLES JILL M. 
Published: June 2024

Introduction & Objective: Pre-eclampsia (PE) is a hypertensive disorder in pregnancy thought to result from abnormal vascular placentation that is associated with metabolic dysfunction. Blood lactate is also associated with metabolic dysfunction. Few studies have explored if lactate is associated with PE. The purpose of this pilot prospective cohort study was to determine if blood lactate is higher among patients with GGI (i.e. an abnormal screening glucose tolerance test (GTT) between 24-28 weeks gestational age) that subsequently developed PE.
Methods: Participants were included if they had GGI and fasting lactate collected during standard 100g GTT. Fasting venous blood was collected to determine lactate, insulin, and glucose and HOMA-IR was calculated. Chi-square, t-test, and Mann-Whitney U analyses were performed to assess differences between groups (PE vs no PE) and binary logistic regression analysis assessed for differences in lactate, to control for pre-pregnancy BMI.
Results: A total of 106 individuals were included in our analysis. Of these, 14 (13%) developed PE and 92 (87%) did not. There were no differences in fasting glucose, insulin, or HOMA-IR between groups. Median fasting lactate level was higher among those who developed PE (1.05mmol/L IQR 0.20 vs 0.9 mmol/L IQR 0.18, p=0.053) and was a significant predictor of PE after controlling for pre-pregnancy BMI (p=0.047).
Conclusion: Our study highlights evidence that fasting venous lactate levels are elevated in pregnant persons with GGI who subsequently develop PE in pregnancy. Future studies should attempt to identify why individuals who develop PE with GGI have increased fasting venous lactate levels.

Disclosure
R. Purvis: None. N. Zite: None. A. Mastronardi: None. O. Oyedeji: None. N.T. Broskey: None. J.M. Maples: None.
1974-LB: Impact of Maternal Hyperglycemic and Hypertensive Disorders on Adverse Pregnancy Outcomes across the COVID-19 Pandemic—A Comprehensive Analysis in an Underserved Population
Authors: ZHANG LIXIA , SHEN YUN , HU GANG 
Published: June 2024

Objective: To evaluate the impact of COVID-19 on the associations between maternal hyperglycemic and hypertensive disorders and adverse pregnancy outcomes.
Methods: This retrospective study included 110,447 Louisiana Medicaid pregnant women with first-time delivery between January 1, 2016, to December 31, 2021. Adverse pregnancy outcomes were collected through Medicaid claim data. Logistic regression adjusted for maternal age and race and ethnicity, with additional interaction analyses were used.
Results: Participants delivered during early and late COVID-19 pandemic had significantly higher risk of these adverse pregnancy outcomes except preterm birth compared with before the pandemic. The incremental risk of preterm birth associated with HDP during late pandemic is not significant (P &gt; 0.10) as well as LGA (P &gt; 0.25; P &gt; 0.10) and macrosomia (P &gt; 0.50; P &gt; 0.10) during early and late pandemic. Participates with pre-existing hypertension delivered during late pandemic had no significant risk of preterm birth (adjusted OR, 1.09 [95% CI 0.86-1.36]). Individuals with normal blood pressure delivered during early pandemic and with preeclampsia or eclampsia delivered during late pandemic had higher risk of LGA (adjusted OR, 1.32 [95% CI, 1.19-1.47]; 1.56 [95% CI, 1.15-2.10]) and macrosomia (adjusted OR, 1.31 [95% CI, 1.18-1.45]; 1.55 [95% CI, 1.16-2.08]). Participates with gestational hypertension and pre-existing hypertension delivered during late pandemic had no significant risk of LGA (adjusted OR, 1.22 [95% CI, 0.86-1.73]; 1.24 [95% CI, 0.88-1.76]) and macrosomia (adjusted OR, 1.27 [95% CI, 0.91-1.77]; 1.18 [95% CI, 0.84-1.67]).
Conclusions: In this large population-based study, associations between hyperglycemic and hypertensive disorders in pregnancy and adverse pregnancy outcomes including preterm birth, LGA and macrosomia varied by COVID-19 pandemic periods.

Disclosure
L. Zhang: None. Y. Shen: None. G. Hu: None.

Funding
This study is supported by the grant from the Public University Partnership Program at the Louisiana Department of Health, Bureau of Health Services Financing. Dr. Hu is partially supported by the grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK132011) and the National Institute of General Medical Sciences (U54GM104940).
1978-LB: Sleep Duration during Pregnancy and Cardiometabolic Biomarkers—A Multiracial Pregnancy Cohort
Authors: CHEN ZIYUAN , YU GUOQI , YIN XIN , ZHANG CUILIN 
Published: June 2024

Introduction & Objectives: Adequate sleep is crucial for maintaining cardiometabolic health, yet its association with cardiometabolic biomarkers during pregnancy remains unclear and inconclusive.
Methods: The study was based on data from a case-control study (N=321) nested in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort (N=2802). Sleep durations were longitudinally assessed by standard questionnaires from early pregnancy through delivery (visit 0: 8-13 gestational weeks (GWs), visit 1: 16-22 GWs, visit 2: 24-29, and visit 4: 34-37 GWs) and categorized into three groups (≤ 6 hours, 7-8 hours, ≥ 9 hours). Plasma cardiometabolic biomarkers, including glucose, insulin, HbA1c, C-peptide, HOMA-IR and C-reactive protein, were measured at the four study visits. Linear mixed models, incorporating both weight and paired stratum, were adopted to estimate associations between sleep duration and cardiometabolic biomarkers, adjusting for potential confounders.
Results: The proportion of participants with sleep duration ≤ 6 hours increased from 15.1% at study visit 0 to 39.6% at visit 4. At study visit 0, women who slept less than 6 hours had higher HbA1c levels than those who slept longer (β = 0.033, 95% CI=0.008, 0.056). Sleep duration ≥ 9 hours at visit 1 was positively associated to insulin level (β =0.208, 95% CI=0.002, 0.415). Besides, compared with sleep 7-8 hours, sleep duration ≥ 9 hours at study visit 2 was significantly and inversely associated with HbA1c, with β= -0.037 (95% CI= -0.070, -0.004), whereas positive association of sleep duration ≤ 6 hours with glucose level was observed at visit 2 (β = 0.153, 95% CI=0.027, 0.279).
Conclusion: Our findings highlight positive associations between less sleep duration and cardiometabolic biomarkers such as glucose and HbA1c at early-mid pregnancy. An adequate sleep may be essential for maintaining cardiometabolic health among pregnant individuals.

Disclosure
Z. Chen: None. G. Yu: None. X. Yin: None. C. Zhang: None.
1982-LB: Prevalence of Autoimmune Antibodies Associated with LADA in Patients Treated with Type 2 Diabetes
Authors: LOMELI LAURA D. , LUNDHOLM MICHELLE D. , XIAO HUIJUN , ZHOU KEREN , PANTALONE KEVIN M. 
Published: June 2024

Introduction & Objective: Prevalence of latent autoimmune diabetes in adults (LADA) is estimated at 3-28.5%. We aim to assess LADA prevalence by measuring a complete panel of autoimmune antibodies (AAbs) in a community-based population of patients (pts) with type 2 diabetes (T2D), managed by endocrinology (Endo) vs primary care providers (PCP).
Methods: This single-center prospective study enrolled 202 adults with T2D without a history of LADA: 100 PCP and 102 Endo pts. AAbs were tested by ELISA: Glutamic Acid Decarboyxlase-65, anti-islet cell, Insulinoma Associated 2, Zinc Transporter 8, and anti-insulin.
Results: Overall, 14% (N=27) of pts tested positive (pos) for AAbs; 16% Endo vs 11% PCP pts (P=0.31). Other differences in Endo vs PCP pts are summarized in Table 1a. After excluding pts pos for only anti-insulin ab (N=12), insulin use was higher in pts AAb pos vs neg (53% vs 18%, P=0.004). There were no other significant differences in BMI, A1c, nor diabetes complications between pts AAb pos vs neg (Table 1b).
Conclusion: AAbs were detected in 14% of pts with T2D; no difference was observed between Endo vs. PCP pts. After excluding pts pos for only anti-insulin ab, just 8% tested pos for at least one AAb. Future studies are needed to evaluate the prevalence of AAbs at the onset of T2D, with longitudinal monitoring for AAb development, to better understand the pathogenesis and significance of identifying LADA among pts with T2D.

Disclosure
L.D. Lomeli: None. M.D. Lundholm: None. H. Xiao: None. K. Zhou: None. K.M. Pantalone: Speaker's Bureau; AstraZeneca. Consultant; AstraZeneca. Board Member; Bayer Inc. Research Support; Bayer Inc. Speaker's Bureau; Corcept Therapeutics. Consultant; Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Research Support; Merck & Co., Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Twin Health. Consultant; Sanofi.

Funding
This study was funded from philanthropic donations made possible by generous donors and an internal granting mechanism: Caregiver Catalyst GrantsInternal (Grant # CCG0178)
1987-LB: Limitations of Artificial Intelligence Research in Predicting Type 2 Diabetes Macrovascular Complications—A Scoping Review
Authors: NUR AQSHA , HARBUWONO DANTE 
Published: June 2024

Over 500 million people were estimated to live with diabetes in 2021, of which 96% were type 2. This leads to various complications, among which are macrovascular diseases (e.g., stroke and coronary heart diseases). As complications increase the 5-year mortality of patients, curbing their progression through early prediction and intervention is key. This scoping review explores the characteristics of current research on how artificial intelligence, including machine learning algorithms, has been utilized to predict diabetes macrovascular complications. In adherence to PRISMA-ScR guidelines, we systematically searched PubMed, Google Scholar, Scopus, IEEE Xplore, EMBASE, and Wiley for relevant literature up to 12 December 2023. Out of the 1,667 hits screened, 52 studies cumulating 7,510,245 people with type 2 diabetes are included. We found 43 studies from HICs/UMICs, in contrast to 9 from LMICs/LICs. 30 studies came from North America and Europe regions, while others from Asia and Australia. Of all macrovascular complications, cardiovascular diseases (e.g., coronary heart disease) have been the most investigated outcome. According to the features of the models, only 12 studies employed non-laboratory features as predictors, while the remaining studies applied solely laboratory (n=2) or mixed (n=38) features, signalling the lack of AI capability for history-taking and physical examination data alone, which are mostly available in low-resource settings. While artificial intelligence is promising in predicting diabetes complications, future studies should explore accessible features in low-resource settings and employ external validation. A systematic review and meta-analysis exploring the performance metrics of a variety of algorithms should be done.

Disclosure
A. Nur: None. D. Harbuwono: None.
1995-LB: Prevalence, Risk Factors, and Clinical Characteristics of NAFLD in Individuals with Type 1 Diabetes Mellitus
Authors: JIANG WEIWEI , HUANG QINGYING , XU WEN , YAN JINHUA , WANG CHAOFAN , YANG DAIZHI 
Published: June 2024

Objective: Nonalcoholic fatty liver disease (NAFLD) prevalence data in age- and BMI-matched reference groups are scarce. We aimed to investigate the prevalence, risk factors, and clinical characteristics of NAFLD in individuals with type 1 diabetes mellitus (T1DM).
Methods: A retrospective study was conducted on 1,132 people with T1DM who attended the Endocrinology Department from January 2014 to December 2022. After screening, a cohort of 832 T1DM patients was included for prevalence investigation. NAFLD diagnosis was based on ultrasound findings. A 1: 2 propensity score matching based on age, sex, and duration of diabetes was performed between the NAFLD and non-NAFLD groups. Additionally, 156 age-, sex-, and BMI-matched controls with normal glucose tolerance were enrolled, with laboratory measurements recorded. The t-test, χ2 test, and nonparametric test were used for comparison between the two groups when appropriate. Multivariate logistic regression models were used to assess risk factors for NAFLD.
Results: 61 individuals of NAFLD were identified among 832 individuals with T1DM, with a lower prevalence compared to the matched controls (7.3% vs 23%, P &lt;0.05). The NAFLD group exhibited higher BMI, glucose, triglycerides (TG), ALT, GGT, and hsCRP levels but lower HDL-C compared to the non-NAFLD group (P &lt; 0.05). Logistic regression analysis showed that BMI (OR= 1.27, 95% CI= 1.16 - 1.51), modified HOMA-IR (OR= 1.04 [1.01,1.08]), GGT (OR= 1.03 [1.01 - 1.05]), and TG (OR= 1.55 [1.19 - 2.13]) were associated with increased risk for NAFLD after adjusting for age, sex, metabolic syndrome, and its components (P&lt;0.001). The predictive model combining BMI, modified HOMA-IR, GGT, and triglycerides demonstrated an area under the curve of 0.823 (95% CI= 0.76 - 0.89).
Conclusion: NAFLD is less prevalent in individuals with T1DM than in matched controls. A model integrating BMI, modified HOMA-IR, GGT, and triglycerides effectively predicts NAFLD risk in this population.

Disclosure
W. Jiang: None. Q. Huang: None. W. Xu: None. J. Yan: None. C. Wang: None. D. Yang: None.
2006-LB: Polygenic Scores for Metabolic Diseases Are Associated with Gene Expression Networks across Tissues
Authors: BRYAN CHRISTOPHER , SMITH KIRK , DASHTI HESAM , CLAUSSNITZER MELINA , MANNING ALISA , MERCADER JOSEP M. , UDLER MIRIAM , HUANG YI 
Published: June 2024

Genetic risk for type 2 diabetes (T2D), coronary artery disease (CAD), and obesity can be estimated with global extended polygenic scores (gePS), which capture risk across thousands of genetic variants. Nevertheless, knowledge of underlying disease pathways remains limited. Expression Quantitative Trait Scores (eQTS) connecting gePS to gene expression could help prioritize disease-causing genes and pathways in specific tissues. We generated gePS for T2D, CAD, and body mass index (BMI) in the Genotype-Tissue Expression (GTEx) database of 838 individuals and 49 tissues. eQTS were calculated using a linear model of association between gePS and tissue transcript expression level, adjusting for age, sex, 5 genetic PCs, and 20 gene expression PCs. Gene set enrichment was performed using Enrichr with Gene Ontology pathway sets and Fisher’s Exact Test (Q &lt; 0.05). T2D, CAD, and BMI gePS were each associated with &gt; 500 transcript expression levels (eQTS) across multiple tissues at p &lt; 0.05. In multiple tissues, both T2D and BMI eQTS were significantly enriched for pathways related to mitochondrial function (Q&lt;10-7), with the most significant T2D signal found in the heart atrial appendage and BMI signals in subcutaneous (SC) and visceral adipose. For T2D, pancreas eQTS were enriched for pancreatic beta cell development and mature onset diabetes of the young (MODY) (Q&lt;10-3). For CAD, cholesterol metabolism pathways were enriched in the coronary artery (Q&lt;10-7). In summary, T2D and BMI eQTS share mitochondrial and metabolic transcription mechanisms across several tissues, including SC adipose. Cholesterol metabolism was enriched in the coronary artery in CAD eQTS. This study provides novel insight into the shared genetic and transcriptomic architecture of T2D, CAD, and obesity.

Disclosure
C. Bryan: None. K. Smith: None. H. Dashti: None. M. Claussnitzer: None. A. Manning: None. J.M. Mercader: None. M. Udler: Other Relationship; Up-To-Date. Y. Huang: None.

Funding
Doris Duke Foundation
2012-LB: Type 2 Diabetes GWAS Signal C2CD4A/B Insulin Resistance Mechanisms in Skeletal Muscle
Authors: EPELLE IBIERE L. , VARSHNEY ARUSHI , ORCHARD PETER , ZHANG ZHENHAO , FENG FAN , LAAKSO MARKKU , TUOMILEHTO JAAKKO , LAKKA TIMO A. , MOHLKE KAREN L. , BOEHNKE MICHAEL , SCOTT LAURA , KOISTINEN HEIKKI A. , COLLINS FRANCIS S. , LIU JIE , PARKER STEPHEN C. 
Published: June 2024

Mechanisms of insulin action differ between fasting and postprandial states across tissues, with postprandial disturbance in insulin action being crucial in the development of type 2 diabetes (T2D). We generated single nucleus (sn-) chromatin accessibility and transcriptome profiles of 287 skeletal muscle biopsies from the FUSION Tissue Biopsy Study. These data found chromatin accessibility quantitative trait loci (caQTL) in muscle fibers colocalized with a T2D GWAS signal and a recently identified C2CD4A/B GWAS signal for insulin fold change (IFC) (coloc PP H4 = 0.969). This chromatin accessibility peak had previously been identified in an islet stretch enhancer and implicated C2CD4A/B in islet dysfunction. However, there has been no formal colocalization with any current islet QTL signals. In our skeletal muscle data, chromatin looping models nominated VPS13C as a candidate target gene. VPS13C encodes a lipid transfer protein. A previous study showed that VPS13C knockdown in an adipocyte cell model decreased insulin-induced translocation and cell-surface abundance of the glucose transporter, GLUT4, thereby implicating this candidate target gene in insulin resistance (IR) mechanisms. We hypothesize that VPS13C modulates IR and T2D risk in skeletal muscle in a cell-type and cell-state-specific manner. We are evaluating the allele-specific activity of the caQTL regulatory element with luciferase reporter assays in the LHCN-M2 human skeletal myoblast cell line. The chromatin looping models predict low contact with the VPS13C transcription start site for the risk allele. Reporter assay results that support this model would suggest a role for VPS13C in glucose uptake mechanisms in skeletal muscle fibers. Moreover, we are generating gene co-expression networks of the sn-transcriptome profiles to identify the network relationships of VPS13C. Collectively, these results will help illuminate the context-specific risk mechanisms at the C2CD4A/B T2D and IR GWAS locus.

Disclosure
I.L. Epelle: None. A. Varshney: None. P. Orchard: None. Z. Zhang: None. F. Feng: None. M. Laakso: None. J. Tuomilehto: Stock/Shareholder; Orion Pharma, Aktivolabs, Digostics. T.A. Lakka: None. K.L. Mohlke: None. M. Boehnke: None. L. Scott: None. H.A. Koistinen: Other Relationship; AstraZeneca, Novo Nordisk. F.S. Collins: None. J. Liu: None. S.C. Parker: Research Support; Pfizer Inc.