bluuebunny/crossref_metadata_2025 huggingface dataset:
1160-P: Continuous Glucose Monitoring in Youth-Onset Type 2 Diabetes—Interim Results from Pilot Randomized Controlled 12-Week Trial
Authors: PATEL TEJAL , ESTRADA DORIS E. , MEYERS ABBY , MACKEY ELEANOR , CHUNG STEPHANIE T.
Published: June 2024

Introduction: Continuous glucose monitors (CGM) may improve diabetes self-management in youth-onset type 2 diabetes (Y-T2D), but feasibility in Y-T2D on infrequent self-monitoring blood glucose (SMBG) regimens and device burden is unclear. This is an interim analysis of primary aims to assess CGM feasibility (recruitment >60%) and acceptability (wear time >60%) and explore diabetes burden and adverse events.

Methods: This is an active 12-week randomized 2:1, two arm parallel pilot trial of CGM vs fingerstick monitoring (Con) in Y-T2D prescribed SMBG <3 times daily (not on multiple insulin injections). Diabetes distress was measured with Diabetes Distress and CGM benefit/burden scale.

Results: Between August-December 2023, recruitment rate was 60% [40 screened, 24 enrolled (14 CGM, 10 Con; 77% female, 69% Black, 14.9±3.8y, BMI: 36.2±7.7 kg/m2, HbA1c: 7.3± 2.6% (mean±SD))]. Most cited reasons for declining were reluctance to wear a device (31%) or study participation (25%). 45% (6 CGM, 5 Con) completed the study; one Con was lost to follow-up. Among CGM, wear time was 62% at 1st 6 weeks [n=11], 49% at 2nd 6 weeks [n=6], and 61% at 12 weeks [n=6], P=0.11. Among Con, blood glucoses were reported in 66% at 1st 6 weeks [n=6] and 20% at 12 weeks [n=5]. 75% of CGM users had sensors dislodged. Diabetes distress score did not change: CGM:1.8 ±0.9 to 1.3±0.1 and control: 1.2±0.2 to 1.2±0.1. No difference in mean CGM burden scale; 17±4.8 to ±7.6.

Conclusion: CGM use in Y-T2D may be feasible but device-related events were common. There is no increase in disease burden with technology use.

Disclosure

T. Patel: None. D.E. Estrada: None. A. Meyers: None. E. Mackey: None. S.T. Chung: None.

Funding

Endocrine Fellows Foundation 2023; Dexcom, Inc
1163-P: Type 2 Diabetes Remission Persists Ten Years after Adolescent Metabolic and Bariatric Surgery
Authors: SISLEY STEPHANIE , SHAH AMY S. , NADEAU KRISTEN J. , KELSEY MEGAN M. , COURCOULAS ANITA , MICHALSKY MARC , JENKINS TODD M. , RYDER JUSTIN R. , INGE THOMAS
Published: June 2024

Introduction: Metabolic and bariatric surgery (MBS) is a safe and efficacious weight loss treatment for children and adolescents with severe forms of obesity. However, there are limited long-term data on treatment effectiveness of MBS for youth-onset type 2 diabetes (YO-T2D). We examined 10-year weight and T2D outcomes among adolescents undergoing MBS.

Methods: We analyzed longitudinal data from 21 individuals who prior to MBS (67% Roux-en-Y gastric bypass, 33% vertical sleeve gastrectomy [VSG]) were < 19 years of age, had ≥ Class 2 obesity and YO-T2D, and were prospectively enrolled in the multi-center, Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study.

Definitions: T2D remission= no prescribed glucose lowering medication and normoglycemia (HbA1c <5.7%); partial remission= no medications and HbA1c 5.7%-<6.5%; no remission= current glucose lowering prescription and/or HbA1c ≥ 6.5%. A fasting blood glucose of <100 mg/dL was substituted for one missing follow-up HbA1c. Data presented as mean±SD or percentage.

Results: At the time of MBS, the cohort was 76% female, 57% non-Hispanic white, and had a mean age of 16.7±1.2 years, BMI 53.9±9.2 kg/m2, and HbA1c 6.8±2.0%. At 10-years post-MBS, 71% of individuals (15/21) experienced remission of T2D and had a 29±18% BMI reduction. Remission rates were similar between surgical types. Twenty-nine percent (6/21) did not experience T2D remission by 10 years post-MBS, and only experienced 4±14% BMI decrease. Of the six individuals without remission at 10 years post-MBS, 3/6 previously had remission (in the interim data collection periods) and one had partial remission 1-year post-MBS, with a return of T2D-range HbA1c in subsequent years.

Conclusion: T2D resolution occurred in a high proportion of adolescents post-MBS, and was durable to 10-years of follow-up. Further study is needed to better understand outcomes in diverse populations of YO-T2D, underlying mechanisms of remission and reasons for low weight loss/lack of remission.

Disclosure

S. Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. A.S. Shah: None. K.J. Nadeau: None. M.M. Kelsey: Other Relationship; Rhythm Pharmaceuticals, Inc., Lilly Diabetes. A. Courcoulas: Research Support; Allurion, Eli Lilly and Company. M. Michalsky: Stock/Shareholder; Intuitive Surgical. Other Relationship; Intuitive Surgical. Advisory Panel; Lilly USA, LLC. T.M. Jenkins: None. J.R. Ryder: None. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex.

Funding

National Institutes of Health (UM1DK072493)
1167-P: Immunological Landscape of Early-Onset Type 1 Diabetes—Cellular Dynamics and Molecular Pathways
Authors: PAN LANXIN , SHI YU , YUE TONG , TAN HUILING , DING YU , LUO SIHUI , GUO CHUANG , ZHENG XUEYING , WENG JIANPING
Published: June 2024

Background: Type 1 Diabetes (T1D) is an autoimmune disease affecting mainly children and young adults. Early-stage immunological understanding is crucial for diagnosis and treatment. This study explores the immune environment in T1D patients' peripheral blood, focusing on early disease phases.

Methods: The study involved 10 T1D patients under 7 years, diagnosed within 1 year, and 10 age- and sex-matched healthy controls. Single-cell RNA sequencing was utilized to analyze peripheral blood samples for disease-related characteristics.

Results: The analysis revealed a distinct immunological profile in T1D, with increased CD14Mono, CD4TEM, and CD4Treg cells and decreased CD4T naïve cells compared to controls. CD14Mono cells in T1D were enriched in stress pathways linked to viral infection and substance transport. Besides immunological and inflammatory traits, CD4TEM cells were associated with enzyme activity and metabolism, while CD4Treg cells focused on cell adhesion pathways. Cell interactions and trajectories indicated transformations among CD4T cells, suggesting CD4Tregs' role in early-stage self-repair, with CXCR4 as a key chemotactic factor.

Conclusion: This study offers a detailed immunological perspective of early-onset T1D, emphasizes the complexity of T1D's immune response and the importance of cellular dynamics and signaling pathways.

Disclosure

L. Pan: None. Y. Shi: None. T. Yue: None. H. Tan: None. Y. Ding: None. S. Luo: None. C. Guo: None. X. Zheng: None. J. Weng: None.

Funding

the National Natural Science Foundation (82100822); the Strategic Priority Research Program of Chinese Academy of Sciences (XDB38000000); the Program for Innovative Research Team of The First Affiliated Hospital of USTC (CXGG02); and the Anhui Provincial Natural Science Foundation (2008085MH248, 2008085MH278)
1212-P: Multiomics Assessment of Transcripts and Genes Associated with Gestational Diabetes
Authors: LONGORIA KAYLA D. , JELLIFFE-PAWLOWSKI LAURA L. , RYCKMAN KELLI K. , BAER REBECCA , OLTMAN SCOTT P. , ASAM KESAVA , FLOWERS ELENA
Published: June 2024

Introduction and Objective: Gestational diabetes (GDM) occurs in 2-10% of pregnant persons annually and is associated with increased morbidities for birthing people and infants. GDM etiology is multifactorial, resulting in diverse risk profiles due to interindividual differences among biological and environmental/behavioral factors. The purpose of this study was to explore transcriptomic and genetic risk factors associated with GDM.

Methods: To examine differential gene expression between pregnant persons with and without GDM (n=16), we analyzed a public dataset (GSE9772) using Deseq2 and a false discovery rate (p-adjusted <0.05). Using data from CA1000 (N = 913), we extended these findings by exploring single nucleotide polymorphism (SNP) prevalence in the solute carrier family 6-member 6 (SLC6A6) gene using Chi-square or Fisher’s exact tests in pregnant persons with and without GDM.

Results: A total of 522 transcripts were differentially expressed (p<0.05) in those with GDM compared to those without, but only SLC6A6 remained significant after correction for multiple comparisons (p-adjusted<0.05). SNP prevalence in the SLC6A6 gene indicated six loci that differed in those with GDM compared to those without (rs13058781 (position 14469836), rs4685160 (position 14476887), rs73030137 (position 14477940), rs9683047 (positions 14486407), rs55957528 (position 14488225), rs17039625 (position 14500806)).

Conclusion: The SLC6A6 gene codes for the taurine transporter protein, and taurine deficiency has been associated with GDM, type 2 diabetes, and poor fetal health and delivery outcomes. Our findings suggest an association between taurine biology and GDM. Future studies are needed to advance understanding of the role of taurine biology in GDM and potential implications of genotype-phenotype interactions in GDM risk.

Disclosure

K.D. Longoria: None. L.L. Jelliffe-Pawlowski: None. K.K. Ryckman: None. R. Baer: None. S.P. Oltman: None. K. Asam: None. E. Flowers: None.
1225-P: Dietary Fiber and Glycemic Control in Women with Diabetes in Pregnancy—A Systematic Review and Meta-analysis
Authors: JONES DANIELLE , KYRIAKIDOU ANNA , COOPER LOUISE , ATTA NOORIA , TOBOLSKA PATRYCJA , SMITH SUZANNE , TURNER ELIZABETH , PETRY CLIVE J. , MEEK CLAIRE L.
Published: June 2024

Dietary fiber improves glycemic control in type 2 diabetes, but its therapeutic role in pregnancy diabetes is unclear. We assessed the effect of dietary fiber on glycemia in women with diabetes in pregnancy.

Methods: We searched three databases (Cochrane Library, MEDLINE, Web of Science) to identify RCTs exploring the effect of dietary fiber, high fiber diets or fiber supplementation on fasting blood glucose (FBG), postprandial blood glucose (PBG), and requirement for insulin therapy in pregnant women with any type of diabetes. Data was pooled for each outcome, and we calculated Hedges’ g from standardised mean differences between groups to estimate effect size.

Results: Of 1,462 identified studies, data from 20 eligible trials containing 1,016 participants were pooled. On meta-analysis, a higher fiber intake was associated with reduced FBG (Hedges’ g= -1.11, 95%CI; -1.92, -3.0), PBG (Hedges’ g= -0.66, 95%CI; -1.17, -0.14), and requirement for insulin (logOR -1.43, 95%CI; -2.07, -0.78). There was significant heterogeneity for FBG and PBG (>90%), attributable to differences in Intervention type (DASH, Low GI, supplement; p<0.01) and study duration <4wks (for PBG: p=0.04; not for FBG). Studies were mostly scored as high risk of bias due to lack of blinding (Cochrane Risk of Bias Tool v.2.0).

Conclusion: High-quality dietary intervention studies in pregnancy are lacking. Our results suggest that high-fiber diets improve fasting and postprandial glycemia and reduce the likelihood of requiring insulin in women with diabetes in pregnancy.

Disclosure

D. Jones: None. A. Kyriakidou: None. L. Cooper: None. N. Atta: None. P. Tobolska: None. S. Smith: None. E. Turner: None. C.J. Petry: None. C.L. Meek: Research Support; Dexcom, Inc.
1230-P: Clinical Risk Factors and First Gestational 75g OGTT May Predict Recurrent and New-Onset Gestational Diabetes in Multiparous Women
Authors: MIRABELLI MARIA , TOCCI VERA , CHIEFARI EUSEBIO D. , PATRIZIA FOTI DANIELA , BRUNETTI ANTONIO
Published: June 2024

Women who had gestational diabetes mellitus (GDM) in their first pregnancy are again prone to GDM in a second pregnancy. Even women with no previous history of GDM may be at risk of GDM in a future pregnancy. Identifying women who are more likely to have recurrent or new onset GDM is important for effective planning of future pregnancies.

Multiparous women (n=759), tested for GDM in two consecutive pregnancies, were retrospectively enrolled. GDM was diagnosed by 75g OGTT (IADPSG criteria). OGTT was performed at 24-28 weeks or earlier in case of a former GDM diagnosis. To compare clinical features and OGTT glucose curves, women were divided into four groups: NGT women at both pregnancies (n=493); women with first occurrence of GDM at their second pregnancy (n=74); women with non-recurrent GDM at second pregnancy (n=92); women with recurrent GDM at second pregnancy (n=100).

Intergroup comparisons revealed clinical predictors of GDM at the first pregnancy (family history of type 2 diabetes, PCOS, early menarche, advanced maternal age, pregravid obesity) and at the second pregnancy (interpregnancy BMI gain), and predictors of recurrent GDM (pregravid obesity, PCOS). Among these women, a positive correlation was observed between the OGTT glucose curves of consecutive pregnancies. Adjusted logistic regression showed that higher level of 1h-postload glucose (ROC optimal cut-point: 130 mg/dL) at the first pregnancy would enhance the likelihood of a new occurrence of GDM in a second pregnancy (OR 2.50, 95%CI 1.51-4.13), whereas higher levels of 2h-postload glucose (ROC optimal cut-point: 153 mg/dL) at the first diagnostic OGTT would enhance the likelihood of GDM recurrence (OR 2.21, 95%CI 1.06-4.63).

Clinical risk factors, and their dynamic changes throughout female reproductive life span, as well as postload glucose at first gestational OGTT, can help predict GDM in multiparous women and tailor preventive interventions, including interpregnancy weight loss.

Disclosure

M. Mirabelli: None. V. Tocci: None. E.D. Chiefari: None. D. Foti: None. A. Brunetti: None.
1238-P: Is Hypoglycemia following Glucose Load Associated with Adverse Neonatal or Maternal Outcomes?
Authors: GOULD ALEXANDER , KASSIR ELIAS , SIAVOSHI MEHRNAZ , KWAN LORNA , HAN CHRISTINA S.
Published: June 2024

Introduction & Objective: Gestational diabetes (GDM) is typically diagnosed by elevated plasma glucose on a screening 50-gram 1-hour oral glucose challenge test (1H), followed by two elevated values on a diagnostic 100-gram 3-hour glucose tolerance test (3H). Pregnancy outcomes of individuals with hypoglycemia (HG) during a 1H or 3H have not been well-studied. We aimed to evaluate risk of adverse neonatal outcomes (ANO) and adverse maternal outcomes (AMO) in pregnancies including HG on a 1H or 3H.

Methods: In this retrospective cohort study, we examined patients who delivered at two academic centers from January 2021-June 2022. Singleton pregnancies with a 1H and/or 3H done 8-16 weeks before delivery were included. Pregnancies with fetal anomalies, pre-gestational DM, gastric bypass and cystic fibrosis were excluded. HG was defined as <70 mg/dL. Patients with HG on 1H or 3H were compared to patients with normal 1H. The primary outcome was a composite of ANO/AMO. Groups were compared using Kruskal-Wallis and Chi-square tests, as appropriate. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated from logistic-regression models.

Results: The cohort included 2,867 pregnancies: 2,146 with normal 1H, 102 with HG on 1H, and 147 with HG on 3H. Differences in demographic and risk factors between groups included maternal age at delivery, race/ethnicity, pre-pregnancy BMI and pre-diabetes, maternal cardiac disease, and total weight gain in pregnancy. After adjusting for these differences, HG following 1H or 3H was not associated with increased risk of ANO/AMO overall (1H ANO: aOR 1.292 [CI 0.734-2.276]; 1H AMO: aOR 1.077 [CI 0.638-1.819]; 3H ANO: aOR 0.883 [CI 0.574-1.358]; 3H AMO: aOR 0.998 [CI 0.654-1.523]).

Conclusion: In this cohort of singleton pregnancies, HG following glucose load was not associated with increased risk of ANO/AMO overall. HG following glucose load may indicate abnormal glucose metabolism, though its clinical significance in pregnancy is unclear.

Disclosure

A. Gould: None. E. Kassir: None. M. Siavoshi: None. L. Kwan: None. C.S. Han: None.
1247-P: Outcomes of Pregnancies Complicated by Type 1 Diabetes in a Diverse Patient Population at an Urban Diabetes Center
Authors: LONIER JACQUELINE , BEJERANO SHAI , EVANS ANABEL , GOLAND ROBIN
Published: June 2024

T1D is associated with increased risk of adverse pregnancy outcomes, which can be mitigated by tight glycemic control. There is a paucity of data demonstrating the outcomes of diverse populations of pregnant women with T1D utilizing current diabetes technology. Here we describe the outcomes of 129 pregnancies in 118 women with T1D who delivered between January 2019 and December 2022, managed by a multidisciplinary diabetes care team at a single center. Of this cohort, 42% identified as non-Hispanic white (NHW), 6% as non-Hispanic Black (NHB), 34% as Hispanic, and 5% as Asian or other; 39% were publicly insured. Insulin pumps were used in 67% of pregnancies, CGMs in 90%, and hybrid closed-loop systems in 38%. The median of the average HbA1c through pregnancy in the entire cohort was 6.0%. Preeclampsia occurred in 28% of pregnancies, preterm delivery (<36 weeks) in 25%, macrosomia in 10%, neonatal hypoglycemia in 13%, NICU admission in 28%, and fetal anomalies in 3%. There were no neonatal deaths. Compared to multiple daily injections, insulin pump use was associated with lower average A1c through pregnancy (median 5.8% vs 6.8%, p<0.001) and lower risk of preterm delivery (21% vs 42%, p=0.03). NHB and Hispanic women had higher average A1c compared to NHW women (respectively median 6.6% and 6.5% vs 5.6%, p<0.001), higher risk of preterm delivery (43% and 48% vs 10%, p=0.001), and neonates with lower birthweight (median 3035g and 3215g vs 3465g, p=0.005). Similar trends of higher risk of adverse outcomes were observed in publicly insured women compared to those with private insurance. Our data demonstrates the feasibility of achieving glycemic targets on a population level in pregnant women with T1D. Concerns remain regarding disparities in outcomes between NHB and Hispanic women compared to NHW women and in those with public vs private insurance. Analyses of larger populations are needed to further delineate these disparities and inform systems-level approaches to care of pregnant women with T1D.

Disclosure

J. Lonier: None. S. Bejerano: None. A. Evans: None. R. Goland: None.

Funding

Columbia University Diabetes Research Center
1260-P: Forecasting Health Disparity Burden of Cardiometabolic Diseases among U.S. Middle-Aged Adults—A Microsimulation Study
Authors: KIM DAVID , WANG LU , MOZAFFARIAN DARIUSH , WONG JOHN B.
Published: June 2024

Background: Understanding the future health disparity burden of cardiometabolic diseases across racial-ethnic and socioeconomic (SES) groups is essential for policy and priority setting.

Methods: Using a validated US Diabetes, Obesity, Cardiovascular Disease microsimulation (DOC-M) model, we predicted absolute and relative changes (Δ) in the prevalence of diabetes, obesity, cardiovascular diseases (CVD), and all-cause mortality over the next 20 years, overall and by racial-ethnic and SES groups (education and income) among the US population aged 40-79 using the NHANES 2017-2020 data (n=5,745, representing 142.5 million).

Results: As the population aged over the next 20 years, our model predicted that all-cause mortality reached 40.9% overall, with the largest increase in non-Hispanic Black adults (46.7%), followed by adults with less than high school education (44.3%). CVD was projected to increase most in Hispanic adults (11.0% to 23.4%, Δ=↑113.5%), adults with high school equivalent education (18.4% to 33.4%, Δ=↑81.7%), and middle-income adults (16.1% to 29.2%, Δ=↑80.9%). Diabetes prevalence would grow the fastest among Hispanic adults (24.3% in 2020 to 52.9% in 2040, Δ=↑118.3%), versus Non-Hispanic Black adults (23.7% to 45.0%, Δ=↑90.2%) and Non-Hispanic White adults (17.1% to 30.0%, Δ=↑75.5%). Although diabetes prevalence would grow fastest among college-educated adults (16.5% to 31.2%, Δ=↑89.3%) and high-income adults (16.1% to 30.3%, Δ=↑88.0%), the greatest burden of diabetes remains among adults with less than high school education (27.0% to 47.0%, Δ=↑74.4%) and low-income adults (25.9% to 44.2%, Δ=↑74.4%).

Conclusion: Our population health model predicts worsening obesity, diabetes, and CVD that will exacerbate health disparities without targeted health interventions and policies.

Disclosure

D. Kim: None. L. Wang: None. D. Mozaffarian: Research Support; National Institutes of Health, Gates Foundation, Kaiser Permanente Fund, National Association of Chain Drug Stores Foundation, Rockefeller Foundation. Consultant; Acasti Pharma, Inc. Board Member; Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart Health, January Inc., Season Health, Validation Institute, Perfect Day, Tiny Organics. Stock/Shareholder; Calibrate, HumanCo. Other Relationship; UpToDate. J.B. Wong: None.

Funding

NIH/NHLBI (R01HL115189)
1261-P: Is Higher A1C in Older Adults with Cognitive and Functional Impairment Enough to Protect against Hypoglycemia?
Authors: CONERY COLIN D. , SLYNE CHRISTINE , LOO URBINA KENYIN , KRAKOFF NOA , BRABANT HALEY , MUNSHI MEDHA , TOSCHI ELENA
Published: June 2024

Background: Older adults with diabetes with cognitive or functional impairment are recommended to have higher A1C. However, impact of higher A1C on CGM metrics in impaired and unimpaired patients are not well studied.

Methods: A cross-sectional analysis of baseline data across three studies was performed in older adults (age ≥65 years) with diabetes on insulin. Demographic and clinical characteristics including cognitive and functional status, and continuous glucose monitoring (CGM) data were reviewed.

Results: Data on 209 participants stratified as unimpaired (MoCA ≥26 and no frailty) and impaired (MoCa <26 and/or frailty ≥1) were analyzed. Compared to the 66 patients with unimpaired status, the 143 patients with impaired status were more likely to live alone, had greater hypoglycemia fear, and high burden of comorbidities (Table 1). Although the impaired patients had higher HbA1c (7.9% ), both unimpaired and impaired patients had high burden of hypoglycemia (time spent <70 mg/dL)(4.4% and 3.2% respectively) and extreme hyperglycemia (time spent >250 mg/dL(13% and 19% respectively).

Conclusion: Liberal A1C goals based on cognitive and/or functional impairment may not protect against risk of hypoglycemia and extreme hyperglycemia in older adults. CGM should be considered for diabetes care decisions in the older population independent of health status.

Disclosure

C.D. Conery: None. C. Slyne: None. K. Loo Urbina: None. N. Krakoff: None. H. Brabant: None. M. Munshi: Consultant; Sanofi. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sanofi.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1268-P: Association of Triglyceride–Glucose Index and Homeostasis Model Assessment of Insulin Resistance with the American Heart Association's Life's Essential 8—A Nationwide Population-Based Study
Authors: WANG SIBO , WANG LIANSHENG
Published: June 2024

Introduction & Objective: Life’s Essential 8 (LE8) is an updated metric released by the American Heart Association for assessing cardiovascular health. This study aimed to investigate the relationship between triglyceride-glucose (TyG) index and homeostasis model assessment of insulin resistance (HOMA-IR), commonly-used insulin resistance-related parameters, and LE8.

Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. LE8 score was measured according to the AHA LE8 algorithm. The association between TyG index and HOMA-IR (exposure), LE8 scores (outcome) and inflammatory marker (C-reactive protein [CRP]) (mediator) was explored using weighted multivariable linear regression, restricted cubic spline (RCS) models, and mediation analysis. Multiple stratified analyses and sensitivity analyses were also performed.

Results: A total of 13,750 participants, representing 186.3 million US non-institutionalized adults, were included. After multivariable adjustments, compared with the lowest quartile, the β with 95% CIs in the highest quartile were -16.61 (-17.47, -15.75) for TyG index and LE8 (P for trend<0.001) and -15.64 (-16.37, -14.91) for HOMA-IR and LE8 (P for trend<0.001). RCS plots showed a linear negative association between TyG index and LE8 and a nonlinear negative association between HOMA-IR and LE8. Besides, this negative association was significantly stronger in women than in men (P for interaction<0.05). Mediation analysis revealed that CRP significantly mediated the relationship of TyG index and HOMA-IR to LE8 scores with mediation proportions of 13.1% and 22.5%, respectively.

Conclusion: TyG index and HOMA-IR were negatively associated with LE8 scores and cardiovascular health in US adults, especially in women, and systemic inflammation was a partial mediator of this association.

Disclosure

S. Wang: None. L. Wang: None.

Funding

Key Clinical Frontier Technology Project of Department of Science and Technology of Jiangsu Province (NO. BE2022806); National Natural Science Foundation of China (NO. 82070367)
127-OR: Identification of Exosomal miRNA as a Novel Causal Biomarker for Cognitive Impairment in Type 2 Diabetes Mellitus—Triangulating Evidence from Mendelian Randomization Analyses and Multicenter Cohort
Authors: BI YAN , YANG SIJUE , ZHANG ZHOU
Published: June 2024

Introduction & Objective: Diabetes elevated cognitive impairment risk. Early identification of at-risk diabetes patients is crucial. This study explores exosomal microRNAs (exo-miRNAs) as potential biomarkers for early detection of cognitive impairment in T2DM.

Methods: Small RNA sequencing was conducted on exosomes from adipose tissue of T2DM patients and healthy controls. Mendelian randomization (MR) analysis was employed to detect the causal effect of miRNAs on cognitive impairment. Diagnostic performance of the candidates was tested in serum samples from a training cohort and validated in a multicenter cohort.

Results: Twenty-six miRNAs were significantly upregulated in adipose tissue exosomes of T2DM patients. MR analyses identified three miRNAs (miR-25-5p, miR-584-5p, and miR-625-5p) that were causally linked to impaired cognitive function (β=-0.016~ -0.012, P<0.05) and dementia (OR=1.06~1.12, P<0.05). The panel of these three exo-miRNAs in serum samples exhibited a robust ability to detect dementia in T2DM patients (AUC= 0.82, 95%CI 0.71~0.96), which was further confirmed in an external validation cohort.

Conclusions: The study revealed a causal link between exo-miRNAs and dementia in T2DM, providing a new perspective for early detection and therapeutic targets of cognitive impairment in T2DM.

Disclosure

Y. Bi: None. S. Yang: None. Z. Zhang: None.
1275-P: Higher Plasma HDL-C Levels Are Associated with a Reduced Risk of Cardiovascular Disease —A 16-Year Follow-up Community-Based Cohort Study in Korea
Authors: EUN YOO SEUNG , HO MOON JOON
Published: June 2024

Low plasma levels of HDL-C have consistently been identified as a predictor of CVD risk. However, the impact of high HDL-C on reducing CVD risk is controversial, with some studies indicating a U-shaped risk pattern. So, we aim to investigate whether the U-shaped risk pattern is applicable to the Korean population. We conducted a 16-year follow-up on a community-based cohort, excluding individuals with a history of cancer, CVD, CKD (GFR< 30 mL/min), or currently on lipid-lowering medication. Participants were categorized into 4 groups : HDL < 40, 40-60, 60-80, and >80 mg/dL. The primary endpoint was incident CVD, which includes acute myocardial infarction, coronary artery disease, and cerebrovascular disease. The secondary endpoint was carotid IMT. Hazard ratios for incident CVD (with reference to HDL-C <40 mg/dL) were 0.81 (P=0.03), 0.77 (P=0.045), and 0.31 (P=0.045) for the 40-60 mg/dL, 60-80 mg/dL, and > 80 mg/dL groups, respectively. Both left and right carotid IMT inversely correlated with HDL-C groups. In this study, we observed that individuals with very high HDL-C plasma level have a lower risk of CVD in the Korean population. Elevated levels of HDL-C are associated with thinner carotid IMT, indicating reduced future CVD risk. Compared to Western populations, Koreans exhibit significantly lower CVD risk with very high HDL-C levels.

Disclosure

S. Yoo: None. J. Moon: None.
129-OR: Increased Triglyceride Levels Are Associated with a Distinct Lipid-Associated Protein Biomarker Profile of Diabetic Foot Ulcers
Authors: PETKOVIC MARIJA , RAGUZ JANA A. , RASMUSSEN ANNE , KIRKETERP-MØLLER KLAUS , JERSIE-CHRISTENSEN ROSA R. , ANDERSEN JONAS H. , KÜMLER THOMAS , ROSSING PETER , VEVES ARISTIDIS , DALGAARD LOUISE T. , SINGH AHLUWALIA TARUNVEER
Published: June 2024

Background and Aims: The substantial challenges to medical regimens of persons with diabetic foot ulcers (DFU) are associated with clinical heterogeneity and poorly defined risk factors. We examined the proteomic profile of newly detected DFUs to identify at-risk patients and propose a strategy for timely interventions.

Materials and Methods: 112 people with type 1 and 2 diabetes, whose ulcer tissue swaps were collected upon the first observation, were included in an observational study. Enrolled persons were categorised according to healing time: fast healing (FH, <40 days), slow healing (SH, >40 days; <6 months), and chronic non-healing (CH, >6 months). After 6 months of follow-up data were obtained from the electronic patient register. Protein profiles of tissue ulcer swaps were assessed using untargeted proteomics and MaxQuant tools. Proteins with less than 3 valid observations per group were excluded. The analysis included a significance level of 0.05 after FDR correction.

Results: Triglyceride levels of 2.5 mmol/l in CH were markedly elevated compared to FH (1.7, p= 0.013). Out of 223 proteins, 46 were highly correlated to plasma lipid and lipoprotein abnormalities. Gene Ontology (GO) and pathway enrichment from Panther.db show that 28 multiple and overlapping pathways are associated with chylomicrons lipoprotein particle remodelling (>100-fold-enrichment, p<0.0001). Furthermore, the dyslipidaemia pattern in CH compared to FH was characterised by the downregulation of HDL-controlling apolipoproteins family members apoA2, 4 (0.7-fold), upregulation of apoC1-3 involved in triglyceride-rich lipoproteins (1.4-fold), as well as the principal cholesterol carrier Apo-E (1.4-fold).

Conclusions: Our findings show consistent wound tissue lipoprotein profile alterations corresponding to a chronic wound phenotype. We plan to validate these findings using multiomics approaches, before integrating them into routine clinical practice.

Disclosure

M. Petkovic: None. J.A. Raguz: None. A. Rasmussen: None. K. Kirketerp-Møller: None. R.R. Jersie-Christensen: None. J.H. Andersen: None. T. Kümler: None. P. Rossing: Other Relationship; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Gilead Sciences, Inc., Novo Nordisk, Eli Lilly and Company, Novartis AG, Abbott Diagnostics. A. Veves: None. L.T. Dalgaard: None. T. Ahluwalia: None.

Funding

Danish Diabetes and Endocrine Academy (DDEA)(NNF22SA0079901); MAP-D-FOOT (NNF23OC0084081)
1294-P: A Novel Electronic Medical Record (EMR) Search Method to Identify Atypical Diabetes Patients
Authors: AHMED MAAZ , KUBOTA-MISHRA ELIZABETH A. , SILLER ALEJANDRO F. , DAVIS ANSLEY E. , MIGACZ ILIANA , SISLEY STEPHANIE , FARUQI JORDANA , SAEED ZEB I. , AHMED SARAH , PHILIPSON LOUIS H. , REDONDO MARIA J. , BALASUBRAMANYAM ASHOK , TOSUR MUSTAFA , STUDY GROUP RADIANT
Published: June 2024

Introduction & Objectives: Efficient automated EMR review methods to identify people with atypical diabetes (DM) for research are lacking. We aimed to develop a novel Python-based Expeditious Program for EMR Review (PEPPER) and assess its efficiency.

Methods: We extracted the list of 1660 youth (<19 yo) with type 2 DM (T2D) seen between 2019-2022 from EMR to identify candidates with A-β+ (autoantibody negative, preserved β-cell function) Ketosis-prone DM (KPD) for enrollment into Rare and Atypical Diabetes Network (RADIANT). We developed PEPPER to identify diabetic ketoacidosis (DKA) occurrence within 6 months (mo) of diagnosis to prioritize individuals for detailed manual chart review for RADIANT eligibility. We also manually reviewed EMR of 100 youth with T2D to identify DKA occurrence within 6 mo of diagnosis without PEPPER for comparison.

Results: PEPPER identified 110 youth with T2D who had DKA within 6 mo of diagnosis. Twenty-one met the RADIANT A-β+ KPD criteria. The time spent to identify those with T2D and DKA was significantly shorter with PEPPER compared to manual review (13.4 ± 3.9 vs. 26.6 ± 9.4 seconds, p<0.001), translating to 6.2 vs. 12.3 hours to review 1660 charts with and without PEPPER. Both methods yielded identical results, confirming PEPPER’s accuracy.

Conclusion: We developed a novel, efficient and reliable EMR review method that could be used on large cohorts to identify research candidates.

Disclosure

M. Ahmed: None. E.A. Kubota-Mishra: None. A.F. Siller: None. A.E. Davis: None. I. Migacz: None. S. Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. J. Faruqi: None. Z.I. Saeed: None. S. Ahmed: None. L.H. Philipson: Research Support; Novo Nordisk, Novo Nordisk Foundation, Dompé, Vertex Pharmaceuticals Incorporated, Imcyse. M.J. Redondo: None. A. Balasubramanyam: None. M. Tosur: None.

Funding

U54 DK118638 and U54 DK118612 (RADIANT Study Group) and K23-DK129821 (MT)
1298-P: Increased Fasting Glucagon-Like Peptide-1 Level Is Associated with Higher Triglyceride–Glucose Index in Type 2 Diabetes Mellitus Patients with Hypertriglyceridemia
Authors: CHIN CHONG SHIAU , SUKOR NORLELA , ROBERT SARAH A. , FONG NG KIM , KAMARUDDIN NOR A.
Published: June 2024

Introduction & Objective: Triglyceride-glucose (TyG) index is a reliable and simple surrogate marker of insulin resistance (IR). Limited studies have been conducted to assess the association between fasting glucagon-like peptide-1 (fGLP-1) and IR estimated by TyG index. We aimed to investigate the association between fGLP-1 and TyG index in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia and to further explore triglyceride or glucose, as parameters of TyG index, was more closely related to fGLP-1.

Methods: A total of 35 T2DM subjects and 27 subjects diagnosed with T2DM + hypertriglyceridemia were recruited. Hypertriglyceridemia was defined as serum triglyceride ≥ 1.7 mmol/L. Plasma total fGLP-1 concentrations was measured by enzyme-linked immunosorbent assay. The TyG index was determined as ln(fasting triglycerides [mg/dL]×fasting glucose [mg/dL]/2).

Results: Total fGLP-1 level was significantly increased in T2DM + hypertriglyceridemia subjects than T2DM subjects (29.44±12.21 pmol/L vs. 18.24±8.79 pmol/L, p=0.02). FGLP-1 level was positively correlated with TyG index (r=0.375, p=0.001) and fasting triglyceride (r=0.395, p=0.02). There was no significant association between fGLP-1 and fasting plasma glucose. Furthermore, linear regression analysis showed TyG index and triglyceride were independently associated with fGLP-1 (Β=0.328, p=0.02; Β=1.58, p=0.047, respectively).

Conclusion: In T2DM patients with hypertriglyceridemia, increased fGLP-1 was associated with higher IR as measured by TyG index. FGLP-1 was not related to glucose as a parameter of the TyG index, but fGLP-1 was significantly associated with fasting triglyceride. Increased fGLP-1 secretion may play a compensatory role in the pathogenesis of IR induced by hypertriglyceridemia.

Disclosure

S. Chong: None. N. Sukor: None. S.A. Robert: None. K. Ng: None. N.A. Kamaruddin: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk, AstraZeneca.

Funding

University Kebangsaan Malaysia (GUP-2017-066); Malaysian Endocrine and Metabolic Society (L12-MEMS6)
1344-P: Socioeconomic Status Patterns in Remote Diabetic Retinopathy Screening Using Teleophthalmology
Authors: JESSICA CRUZ MARIA , CHOKSHI TANVI , NGUYEN LINDSEY , VARGAS-RAMOS TREYSI G. , HANG ABRAHAM , SNYDER BLAKE M. , YIU GLENN
Published: June 2024

Purpose: Diabetic retinopathy disproportionately affects groups from disadvantaged backgrounds. Although teleophthalmology improves diabetic retinopathy (DR) screening rates, the impact of socioeconomic status on retinal disease severity and remote eye care access is unknown. Here, we investigate whether socioeconomic condition as measured by Area of Deprivation Index (ADI) impacts the prevalence and severity of ocular pathologies and eye care follow-up after remote eye screening.

Methods: We reviewed medical records of patients from University of California, Davis Health who underwent remote diabetic retinopathy screening between 2018-2022 to collect demographic data, medical history, teleophthalmology findings, and in-person eye care follow-up reports. ADI is a composite measure of income, education, employment, and housing, which has been used to inform health policy. Patients with no census neighborhood level data were excluded.

Results: Among 1533 patients who underwent remote DR screening (mean age 61.5, 46.4% female, 11.9% Black, 16.1% Hispanic, mean HbA1c 7.6), most patients had no (78%) or mild DR (11.7%), while some had more than mild non-proliferative DR (2.1% moderate, 0.3% severe, 0.3% proliferative, 1.2% diabetic macular edema). Patients with greater socioeconomic disadvantage was associated with worse DR severity (p<0.001). For those who were referred for in-person eye care evaluation (n = 398), the most socioeconomically deprived individuals were also less likely to follow up within the recommended time frame (23.5% in 5th quintile vs. 65.6% in 1st quintile).

Conclusion: Socioeconomic disadvantage as measured by ADI is independently associated with worse DR severity, and less likely to receive follow-up care within the recommended time frame after remote DR screening using teleophthalmology. Although remote DR screening improves overall screening rate, further investigation is needed to understand methods to best mitigate these disparities.

Disclosure

M. Cruz: None. T. Chokshi: None. L. Nguyen: None. T.G. Vargas-Ramos: None. A. Hang: None. B.M. Snyder: None. G. Yiu: Consultant; 4DMT, AbbVie Inc., Adverum Biotechnologies, Alimera Sciences, Bausch + Lomb, Boehringer-Ingelheim, Clearside, Endogena, Genentech, Inc., Gyroscope, Iridex, Janssen, jCyte, Myrobalan, NGM Bio, Novartis, Ray, RegenXBio, Stealth.
1347-P: Risk of Primary Liver Cancer following New-Onset of Diabetes—A Longitudinal Study in a Chinese Adult Cohort
Authors: QI XIAOLONG , LI YILING , ZHANG SHUAIRAN , LIU CHUAN , WANG SHAN , GAO JINGLI
Published: June 2024

Introduction & Objective: Primary liver cancer (PLC) is a major global health concern, with diabetes mellitus (DM) identified as a potential risk factor. Our study aimed to evaluate the temporal association between the onset of DM and the risk of developing PLC.

Methods: A retrospective cohort study was conducted, encompassing a sample of 89,243 Chinese adults free from any previous diagnoses of cancer or DM. Incidence rates of new-onset DM and PLC were recorded over a median follow-up of 14.04 years. Data from biennial health assessments between 2006 and 2020 were analyzed using Cox proportional hazards models, adjusting for demographics and lifestyle factors.

Results: Of the participants, 13,225 developed incident DM. Those with new-onset DM exhibited a higher risk of PLC within the first five years post-diagnosis (HR 3.09), which declined over time (Figure). HBsAg-positive individuals with recent-onset DM faced an even higher risk (HR 4.30). Subgroup analysis identified males, non-obese, current drinkers, and smokers as high-risk groups for PLC among those with new-onset DM.

Conclusion: The onset of DM is associated with a heightened risk of PLC, especially within the first five years following diagnosis, particularly for those with concurrent HBsAg positivity. Our findings highlight the need for vigilant PLC screening in newly diagnosed diabetic patients.

Disclosure

X. Qi: None. Y. Li: None. S. Zhang: None. C. Liu: None. S. Wang: None. J. Gao: None.
1349-P: Diabetes in Chronic Pancreatitis Is Characterized by Significant Insulin Deficiency
Authors: KUDVA YOGISH C. , LI YISHENG , WANG FUCHENCHU , YADAV DHIRAJ , ANDERSEN DANA K. , SAEED ZEB I. , BELLIN MELENA , FISHER WILLIAM E. , CUSI KENNETH , PARK WALTER , RAZA RIZVI SHAFAQ , TOLEDO FREDERICO G. , CONSIDINE ROBERT V. , SERRANO JOSE , GOODARZI MARK O. , HART PHIL
Published: June 2024

Objectives: Chronic pancreatitis (CP) is associated with a high lifetime prevalence of diabetes mellitus (CPDM). However, our understanding of the pathophysiology of CP-DM in contrast to type 2 DM (T2DM) remains incomplete.

Method: We used a mixed meal tolerance test (MMTT 120 min) to assess metabolic alterations in 170 participants with CPDM or with T2DM < 3 years. The DM duration in CP was dichotomized as ≥ or < 3 years. We compared estimates of insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), and beta cell function (oral disposition index or ODI) between subgroups using Wilcoxon rank-rum tests.

Results: Area under the curve (AUC) for glucose was increased, while measures of insulin secretion were reduced in CPDM vs T2DM (Table 1). Glucagon and GIP did not differ. Insulin sensitivity was increased in CPDM <3 yrs but this cohort differs from T2DM with BMI being lower. Interestingly, CPDM ≤ 3 yrs and CPDM >3 yrs did not show any significant differences in insulinogenic index, Matsuda index and ODI.

Conclusion: The most important difference seen in both CPDM cohorts was a significant reduction in insulin secretion. Future studies are needed to understand how these differences can be used to develop personalized anti-hyperglycemic therapy for this patient population.

Disclosure

Y.C. Kudva: Research Support; Dexcom, Inc. Other Relationship; Tandem Diabetes Care, Inc., Medtronic. Y. Li: Stock/Shareholder; Agenus, Inc., Mink Therapeutics, Inc. F. Wang: None. D. Yadav: Consultant; Pfizer Inc. Research Support; AbbVie Inc. D.K. Andersen: None. Z.I. Saeed: None. M. Bellin: Research Support; ViaCyte, Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated, Insulet Corporation. Research Support; Dexcom, Inc. W.E. Fisher: Other Relationship; Intuitive Surgical. K. Cusi: Research Support; Echosens, Boehringer-Ingelheim, Quest Diagnostics, Inventiva Pharma, LabCorp, Nordic Bioscience A/S. Consultant; Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer-Ingelheim, Lilly Diabetes, 89bio, Inc., GlaxoSmithKline plc, Novo Nordisk, Siemens Healthcare Diagnostics, Sagimet Biosciences, Terns Pharmaceuticals. W. Park: Research Support; AbbVie Inc. Advisory Panel; Pfizer Inc. Consultant; Arctx Medical. Advisory Panel; Ariel Medicine. Consultant; Capsovision, Olympus. Advisory Panel; Horizon Therapeutics plc, Nestlé Health Science. S. Rizvi: None. F.G. Toledo: Advisory Panel; Sanofi. Research Support; Dompé. R.V. Considine: Research Support; Eli Lilly and Company, Adipo Therapeutics. J. Serrano: None. M.O. Goodarzi: Advisory Panel; Nestlé Health Science, Organon. P. Hart: None.

Funding

NIDDK (U01DK108327)
1356-P: Factors Associated with Liver Fibrosis in Type 2 Diabetes Mellitus
Authors: PULZ GEORGIA T.C. , DE ALMEIDA PAULA , MULLER GUILHERME R. , JUNG MAITHÊ K. , COPATTI VITÓRIA , FRIEDRICH MARIANGELA G. , FACCIN CARLO S. , DE FRAGA RAQUEL S. , LEITAO CRISTIANE B.
Published: June 2024

Introduction & Objective: risk factors for liver fibrosis in metabolic associated steatotic liver disease are not clear in T2DM patients. We aimed to assess clinical, laboratory and body composition factors associated with liver stiffness in T2DM.

Methods: individuals >18 years attending the T2DM outpatient clinic were included in a cross-sectional study. Clinical, biochemical, anthropometric and body composition data were collected. Liver steatosis and stiffness were evaluated (ultrasound and elastography). Data were analyzed by x², t test and logistic regression.

Results: from 664 medical records reviewed, 204 met inclusion criteria and were included. So far, 87 patients were evaluated. Forty-one (47%) patients had mild, 13 (15%) moderate and 2 (2%) severe liver steatosis. In elastography, 54 (65%) patients had no liver stiffness (≤5 kPa), while 28 had some degree (5 - 9 kPa n = 19; >9 kPa n = 9). Variables associated with liver stiffness are depicted in Table 1. In multivariate analysis, ALT and BMI remained associated with higher liver stiffness. Similar results were observed when BMI was switched for total fat mass, trunk fat or limbs fat mass. NFS was the only score associated with liver stiffness.

Conclusion: ALT and parameters of fat mass were independently associated with higher liver stiffness. Notably, NFS performed better than FIB-4 score. Global fat mass, rather than fat in a specific body segment, is associated with higher risk for liver stiffness.

Disclosure

G.T.C. Pulz: None. P. de Almeida: None. G.R. Muller: None. M.K. Jung: None. V. Copatti: None. M.G. Friedrich: None. C.S. Faccin: None. R.S. De Fraga: None. C.B. Leitao: None.
1360-P: Racial Disparities in Selected Complications and Comorbidities among People with Type 2 Diabetes
Authors: HACKL CAITLIN M. , LEE WEI-CHEN , SALLAM HANAA , SERAG HANI
Published: June 2024

Introduction & Objective: T2DM is a growing public health concern differentially impacting racial and ethnic minorities. To achieve the Centers for Disease Control and Prevention’s Division of Diabetes Translation goal to reduce disparities in diabetes outcomes, assessing disparities is the first step in designing plans to address them.

Methods: We analyzed data from patients (18 years+) diagnosed with T2DM between 01/01/2012 and 03/31/2017 using electronic records of a single health system. We employed Chi-Square to compare selected micro and macro-vascular complication age-standardized rates, associated obesity, and insulin dependence among racial and ethnic groups.

Results: Our sample included 20,680 patients who made 394,106 visits (9,922 non-Hispanic Whites, 4,698 non-Hispanic Blacks, and 6,060 Hispanics). Our results suggest a higher risk of acquiring selected macrovascular (hypertension, ischemic disease, and stroke) and microvascular (renal, ophthalmic, and neurological) complications in Blacks compared to non-Hispanic Whites and Hispanics (p<0.0001). Rates of stage I or II obesity were 62.6% in Blacks, 59.7% in Whites, and 60.0% in Hispanics (p<0.0007 and p=0.0051 for Blacks vs. Whites and Blacks vs. Hispanics; respectively). Rates of insulin use rather than oral hypoglycemics were 52.9% in Blacks, 48.6% in Whites, and 49.7% in Hispanics (p<0.0001 and p=0.0012 for Blacks vs. Whites and Blacks vs. Hispanics; respectively).

Conclusion: Our study suggests a higher susceptibility to complications among Black patients. These disparities are possibly linked to the socioeconomic disadvantages of this patient population leading to poorer management. Prevention strategies are warranted to reduce the incidence of T2DM complications in racial minorities.

Disclosure

C.M. Hackl: None. W. Lee: None. H. Sallam: None. H. Serag: None.