bluuebunny/crossref_metadata_2025 huggingface dataset:
1173-P: CGM Detection of Undiagnosed Celiac Disease in Children with Type 1 Diabetes
Authors: RUIZ JESSICA , ASARO LISA , BERNIQUE ALLISON , CLEMONS SARAH , SILVESTER JOCELYN A. , WYPIJ DAVID , AGUS MICHAEL
Published: June 2024

Celiac disease (CD) results in enteropathy and malabsorption that can cause prandial insulin-glucose mismatch in patients with type 1 diabetes (T1D). This study leveraged continuous glucose monitoring (CGM) in children during the first year after T1D diagnosis to determine whether those with untreated CD have lower post-prandial glucose levels compared to those without CD. Children with T1D, positive CD serologies and biopsy-confirmed CD (CD+) were matched 1-to-4 to children with T1D but negative CD serologies (CD-) on age, sex, BMI and duration of diabetes. Meals were analyzed in the 30-day window before CD serologies and were computationally defined as paired CGM glucose peaks and troughs. Differences in the primary outcome, post-prandial trough, and other post-prandial glucose variables were assessed via log-linear mixed models. The cohort (N = 16 CD+, N = 64 CD-) was 69% female, with median age 10.7 years (interquartile range 8.9 - 12.8), T1D duration 4.1 months (2.3 - 7.7), and BMI z-score 0.29 (0.00 - 0.92). Over the 30-day window, mean post-prandial trough glucose and peak glucose were 111.7 mg/dL (SD 36.3) and 213.6 mg/dL (48.5) in the CD+ children, and 128.6 mg/dL (39.8) and 238.4 mg/dL (53.0) in the CD- children, respectively. In the repeated measures models, CD diagnosis reduced trough glucose by 12.8% (p = 0.059) and reduced peak glucose by 10.2% (p = 0.048). Other secondary outcomes including change in glucose or time from peak to trough did not significantly differ between groups. There is a quantifiable difference in post-prandial glucose when CD is present and untreated in patients with T1D. These findings can inform a future, CGM-based, predictive model of CD in T1D to prompt screening and aid in earlier diagnosis and treatment.

Disclosure

J. Ruiz: Research Support; Dexcom, Inc. L. Asaro: None. A. Bernique: None. S. Clemons: None. J.A. Silvester: Consultant; Takeda Pharmaceutical Company Limited. Research Support; Takeda Pharmaceutical Company Limited. Other Relationship; Wolters Kluwer Health. D. Wypij: None. M. Agus: Research Support; Dexcom, Inc.

Funding

Cystic Fibrosis Foundation ù Pediatric Scientist Development Program (K12-HD000850)
1178-P: Autoantibodies Specifically Targeting Oxidative Post-translationally Modified Insulin in Type 1 Diabetes
Authors: JIA XIAOFAN , POZZILLI PAOLO , NISSIM AHUVA , STROLLO ROCKY , YU LIPING
Published: June 2024

Introduction & Objective: Antibodies to oxidative post-translational modifications of insulin (oxIAA) have been reported in patients with type 1 diabetes (T1D). The specificity of oxIAA related with natural insulin autoantibodies (IAA) is yet to be established.

Methods: Oxidized insulin (•OH-INS) was generated by exposing insulin to hydroxyl radical. The method for detecting autoantibodies to •OH-INS (oxIAA) in the present study used an electrochemiluminescence (ECL) assay as previously used for IAA. In total, 539 samples were tested including 254 from healthy children negative for all islet autoantibodies and 285 from T1D patients newly diagnosed within 2 weeks. Radio-binding assays were performed for all islet autoantibodies (IAA, GADA, IA-2A and ZnT8A) for all participants. Absorption assays for oxIAA were performed using both insulin and OH-INS.

Results: With the specificity set at 95% of 254 controls, the sensitivity of oxIAA was 16.8% (48/285) in patients with new-onset T1D. Of 48 positives for oxIAA, 31 were IAA positive and 17 were IAA negative. Eight sera positive for oxIAA from T1D patients were randomly selected for absorption assay including 4 positive for both oxIAA and IAA, and 4 positive only for oxIAA. The oxIAA from all 8 sera studied were able to be completely absorbed by •OH-INS while the absorption by insulin were poor, showing partial absorption.

Conclusion: Autoantibodies targeting oxidative post-translationally modified insulin can be detected in patients with new onset T1D. The present data that the oxIAA were present in IAA-negative patients and oxIAA were absorbed by •OH-INS, better than natural insulin, demonstrated that oxIAA (specifically against •OH-INS) are novel antibodies in T1D. Further study in pre-T1D subjects will be focused on oxIAA as new risk biomarker of T1D development.

Disclosure

X. Jia: None. A. Nissim: None. R. Strollo: None. L. Yu: None.

Funding

NIH DK032083 DRC P30 DK116073
119-OR: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Ultra-Long-Acting GLP-1 Receptor Agonist (ZT002) in Healthy Subjects
Authors: ZHANG YUANYUAN , XU XIUSEN , MCLENDON KRISTI , WONG ALEX H.L. , ZHANG YUYING , ZHANG XUJIA
Published: June 2024

Introduction: ZT002, a novel ultra-long-acting GLP-1RA, is designed for monthly or biweekly subcutaneous administration and has non-inferior efficacies and a safety profile to semaglutide. Preclinical pharmacokinetics (PK) studies in multiple species (mouse, rat, minipig, monkey) demonstrated ZT002 had a 2-4 fold longer half-life than semaglutide. This first-in-human study assessed the safety, tolerability, PK, and pharmacodynamics (PD) of single ascending doses (SAD) of ZT002 in healthy subjects.

Methods: This phase 1, randomized, double-blind, placebo-controlled, SAD trial was conducted in Australia. Overtly healthy adults 18-55 years with the body mass index of 22.0-35.0 kg/m2 were randomized (6:2) to receive ZT002 (0.03, 0.09, 0.13 and 0.26 mg/kg) or placebo.

Results: A total of 32 subjects [N=20 (male)/12 (female); median age=28 years; median BMI=26.7 kg/m2)] participated in the SAD trial. There were no serious adverse events, deaths or treatment-emergent adverse events (TEAEs) that led to withdrawal. The most common TEAEs related to the study drug were gastrointestinal (nausea and vomiting), and the majority were considered mild and transient. The PK profile was dose-proportional over the dose range with a mean half-life of 260-273 hours, supporting a monthly or biweekly injection. Weight loss from baseline at Day 15 was dose-responsive across the 4 cohorts, and the mean reduction in body weight (BW) from baseline on Day 14 was 2.01 kg in subjects with 0.26mg/kg ZT002 and clinically meaningful weight reduction, in comparison to the placebo, was maintained up to Day 71.

Conclusion: This SAD trial of ZT002 demonstrated acceptable safety, tolerability profile, and superior PK profiles. Significant reductions in BW were observed in healthy subjects. Further clinical development of ZT002 as a monthly or biweekly injectable therapy for obesity and type 2 diabetes mellitus (T2DM) is underway.

Disclosure

Y. Zhang: Employee; QL Biopharmaceutical Co. Ltd. X. Xu: Employee; Beijin QL biopharmaceutical Co., ltd. K. McLendon: None. A.H.L. Wong: Employee; Beijing QL Biopharmaceutical Co., Ltd. Y. Zhang: None. X. Zhang: Employee; QL Biopharmaceutical Co. Ltd.
1195-P: Remote Self-Monitoring of Blood Glucose (SMBG) in Youth with Preclinical Type 1 Diabetes (T1D)
Authors: PAULEY MEGHAN E. , GENO RASMUSSEN CRISTY , BAUTISTA KIMBERLY A. , MUNOZ MARICELA , TAKI IMAN , SEPULVEDA FLOR , BAXTER JUDITH , REWERS MARIAN , SIMMONS KIMBER M.
Published: June 2024

Introduction & Objective: Screening for preclinical T1D and early-stage monitoring are typically only accessible in research studies, but will likely soon expand to clinical settings. Potential strategies for conducting monitoring of early-stage T1D in clinical settings must be explored. This study assessed feasibility of remote SMBG in youth with preclinical T1D.

Methods: Participants from the Autoimmunity Screening for Kids (ASK) study were eligible if enrolled in ASK ≥6 months prior to this study’s start. Upon enrollment in the SMBG study, participants transitioned to an advanced technology glucometer (OneTouch Verio Reflect®) with remote data sharing capability. 12 months of remotely transferred SMBG data was collapsed into 3-month sums and SMBG frequency was explored with Poisson regression.

Results: Data from 42 participants were included (age 13 ± 4.1 years, 62% non-Hispanic white, 62% female, 17% T1D first-degree relative). Frequency of SMBG was highest in the first 3 months (median [IQR]: 3.0 [1.0-8.5]). SMBG frequency decreased over time; there were fewer SMBG in months 4-6 (1.0 [0.0-4.3]), 7-9 (0.0 [0.0-2.3]), and 10-12 (0.0 [0.0-2.0]) (p<0.0001).

Conclusion: Use of devices with remote data transfer is one potential tactic to support clinicians in conducting early-stage T1D monitoring. Strategies to sustain engagement are needed; qualitative studies may provide insight into barriers.

Disclosure

M.E. Pauley: None. C. Geno Rasmussen: None. K.A. Bautista: None. M. Munoz: None. I. Taki: None. F. Sepulveda: None. J. Baxter: None. M. Rewers: Advisory Panel; Sanofi. Other Relationship; Sanofi. Consultant; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Consultant; Provention Bio, Inc. Research Support; Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases. K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic.

Funding

JDRF (2-SRA-2022-1270-S-B); NIH NIDDK (T325T32DK063687); DiabDocs Physician-Scientist Career Development Award: NIH NIDDK (K12DK133995) & The Leona M. and Harry B. Helmsley Charitable Trust to Stanford University (2305-06041)
1199-P: Tackling Transition of Care of Young Adults with Type 1 Diabetes—Preliminary Findings
Authors: DIAS ALEXANDRA A. , CONSIDINE ELIZABETH G. , WEYMAN KATE , CARR DANIELLA , TICHY EILEEN M. , SHERR JENNIFER L.
Published: June 2024

Introduction & Objective: Young adults (YA) with T1D have the greatest deviation from targeted glycemia. The transition of care from pediatric to adult providers may be cumbersome and lead to delays in follow up (f/u). To identify methods to tailor the process and augment transition of care, a feasibility study is underway at our tertiary care center.

Methods: In this prospective study, 15 YA (≥18y/o) with ≥1y T1D duration were recruited. The Readiness for Emerging Adults with Diabetes Diagnosed in Youth (READDY) tool was completed at baseline. Results guide education during f/u visits (initial, 3- and 6-mo after enrollment) and structured visits with social work and nutrition.

Results: Fifteen YA (age: 22.9 ± 1.4y, duration: 15.3 ± 4.6y, HbA1c/GMI median: 6.9% (range 6.0-9.9), pump: 87%, male: 53%) enrolled, with 3-mo f/u completed by 46%. The figure shows average score for each participant for the 4 core domains. The knowledge domain was below average for 26% of the cohort, with specific deficits noted in complications, HbA1c, impact of substances on glucose, and reproductive health.

Conclusion: Implementation of the READDY tool has identified individualized areas requiring focus in the pre-transition period in our feasibility study. Structured topics to be covered based on knowledge deficits and a multidisciplinary approach will be used to assess whether gaps can be mitigated by the 6-mo f/u when the READDY tool will be re-administered.

Disclosure

A.A. Dias: None. E.G. Considine: None. K. Weyman: None. D. Carr: None. E.M. Tichy: None. J.L. Sherr: Consultant; Medtronic. Advisory Panel; Medtronic, Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Vertex Pharmaceuticals Incorporated, MannKind Corporation, StartUp Health T1D Moonshot, Bigfoot Biomedical, Inc., Cecelia Health. Speaker's Bureau; Zealand Pharma A/S.

Funding

Friends of Yale New Haven Children's Hospital
1211-P: In Utero Diabetes Exposure to Diabetes Alters MicroRNA Abundance in Mesenchymal Stem Cells
Authors: KIM YOUNGSIL , HAN LEE WAI , TEAGUE APRIL M. , TRYGGESTAD JEANIE B.
Published: June 2024

Adverse intrauterine environments increase susceptibility of offspring to develop metabolic diseases later in life through epigenetic mechanisms. Studies suggest the multipotent mesenchymal stem cells (MSC) from umbilical cord Wharton’s Jelly are programmed by exposure to maternal diabetes and obesity toward adipogenesis. MicroRNAs (miRNA) are a key mechanism through which epigenetic modifications occur. We hypothesized MSCs exposed to diabetes in utero would have altered miRNA abundance, resulting in downstream effects within the adipogenesis pathway. We harvested human MSCs from control (N=11) and diabetic mellitus (DM, N=13) groups. Control group is defined as mother with normal glucose level and DM with either type 2 diabetes or gestational diabetes during pregnancy. MSCs were isolated within 24 hours of delivery and confirmed via flow cytometry by the presence of CD105 and 90 and absence of CD34 and 45. MSCs were differentiated into adipocytes. Total RNA was extracted using miRNeasy isolation kit (Qiagen, USA) and complementary DNAs (cDNA) from the RNAs were synthesized by using Advance cDNA Synthesis kits (ThermoFisher, USA). Real time PCR (RT PCR) was used to investigate differences in miRNA abundance between those groups. Data from RT PCR were analyzed by delta-delta CT (2−ΔΔCT) method, and RNU48 was used as a reference gene. We discovered that for undifferentiated MSCs, miR-155 was 2-fold higher (p=0.02) and miR-423 was 1.3-fold higher (p=0.04) in the DM comparing to the control group. None of the miRNA in the differentiated adipocytes was different between the groups. Higher levels of miR-155 inhibits browning of fat, and miR-423 is associated with morbid obesity.

In conclusion, DM during pregnancy alters miRNA abundance in stem cells and this phenomenon may impact downstream targets and pathways leading to increased risk of metabolic disease in the offspring.

Disclosure

Y. Kim: None. W. Lee: None. A.M. Teague: None. J.B. Tryggestad: Other Relationship; Ascendis Pharma A/S.

Funding

National Institutes of Health (1K23 DK106533); National Institutes of Health (R03DK125626)
1216-P: Maternal Obesity and Human Milk Metabolomics—Unraveling the Link to Infant Obesity Risk
Authors: DECICCO LEWIS , GARRETT TIMOTHY J. , LEMAS DOMINICK J.
Published: June 2024

Background: Maternal obesity is associated with increased risk of pediatric obesity and the mechanisms that account for these observations remain poorly characterized. Pre-pregnancy BMI (ppBMI) is associated with variation in human milk composition, suggesting that human milk metabolites may affect infant growth and risk of obesity.

Objective: The purpose of this study was to leverage clinical metabolomics to understand the impact of ppBMI on human milk composition in a longitudinal birth cohort.

Methods: Clinical data (n=83) for this study included normal weight (NW, pre-pregnant BMI <25.0 kg/m2) and obese (Ob, pre-pregnant BMI >30.0 kg/m2) maternal infant dyads at 3rd trimester (34-38 weeks) and followed for 12-months postpartum. Human milk samples were collected at 2-weeks and metabolomics data was generated by untargeted high-resolution liquid chromatography mass spectrometry. T-test was performed using the R statistical software to test for differences in human milk metabolomics.

Results: We found that maternal obesity was associated with changes in 170 human milk metabolites. Specifically, we found ppBMI was associated with reduced levels of human milk carbohydrates (deoxyribose, p=0.03), lipids (undecanoic acid, p=0.03), and phytochemical (pipecolate, p=0.02) compounds. We also found that ppBMI was associated with increased levels of lipids (dodecylaldehyde, p=0.02), nucleic acids (uridine, p=0.04) and peptides (ornithine, p=0.0003).

Conclusion: Our results demonstrate that maternal ppBMI was associated with changes in human milk composition and may represent a potential milk-dependent mechanism for mother-child transmission of obesity risk.

Disclosure

L. DeCicco: None. T.J. Garrett: None. D.J. Lemas: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01DK115632)
1223-P: Assessing the Impact of the "Management of Maternal (MOMs) Diabetes Program" in South Carolina
Authors: FU DONGXU , LEYVA MISTI J. , SCHELLINGER MEGAN M. , CAMPBELL BERRY A. , CART COURTNEY U. , FINNERAN MATTHEW , BRITT JESSICA , LILAVIVAT USAH , SMITH MAKALA K. , MANSON MAEGAN E. , HUNT KELLY J. , LYONS TIMOTHY , DIABETES PROGRAM OF SC MOMS
Published: June 2024

Introduction & Objective: In South Carolina, risks of pregnancy associated with maternal diabetes are worsened by disparities. Expert team-based care that is equitable, feasible, meets real-life needs, and improves communication is essential. Objective: to improve pregnancy outcomes through a ‘Management of Maternal (MOMs) Diabetes Program’ implemented at three centers across SC, intended to provide a ‘one stop shop’ and utilize new technologies.

Methods: We compared outcomes for 948 MOMs patients (13% Type 1, 31% Type 2, and 56% gestational diabetes A2: 2020-2023) with 680 ‘standard care’ comparator patients (‘COMP’, from chart abstractions, Medical University of South Carolina perinatal database: 2017-2019). Maternal age and ‘diabetes type’ distributions were similar between groups, but COMP had a higher proportion of Black patients (52.1% vs. 24.8%) and fewer categorized as Hispanic or ‘other’. Two Proportion Z-Tests (two-tailed) were used for statistical analyses, with/without adjustment for race.

Results: Maternal and infant outcomes in MOMs vs. COMP are shown for all patients and for Black and White patients (Table 1).

Conclusions: Despite COVID-19, the MOMs program reduced C-sections, pre-term birth and neonatal hypoglycemia, and improved APGAR scores. Emphasizing the challenge of racial disparities, benefits were greater for White than Black patients.

Disclosure

D. Fu: None. M.J. Leyva: None. M.M. Schellinger: None. B.A. Campbell: None. C.U. Cart: None. M. Finneran: None. J. Britt: None. U. Lilavivat: None. M.K. Smith: None. M.E. Manson: None. K.J. Hunt: None. T. Lyons: None.

Funding

BlueCross BlueShield of South Carolina Foundation (2020-09,2020-08); Duke Endowment (6877-SP)
1233-P: Early Intervention in Pregnant Women with Preconception History of Glucose Intolerance
Authors: FARROKHI FARNOOSH , WILCOX JOSEPH , PARISE CAROL
Published: June 2024

Introduction: Diabetes in pregnancy is associated with greater risks. Previous studies focused on early screening of women with variety of risks for gestational diabetes mellitus (GDM), this study focused on women with preconception history of prediabetes or GDM.

Methods: A retrospective query of the electronic health record was conducted to identify deliveries of women with preconception prediabetes or GDM 1/1/2018 - 10/30/2022 at 4 large centers of Sutter Health in Northern California. Patients with history of diabetes were excluded. Primary aim was to assess characteristics of deliveries underwent early (≤20 weeks) vs standard of care intervention (>20 w) for GDM. Secondary aim was to compare pregnancy outcomes between the groups. Early intervention was defined as any of the following that was done ≤20 weeks: glucose tolerance test, prescriptions related to diabetes, referrals for diabetes management.

Results: Total of 1,954 birth deliveries included, 622 (32%) underwent early, 1,332 (68%) had standard intervention. Women in early group were older (35.8±4.1 vs 35.25±4.4, p=0.01), heavier (preconception BMI 29.3±6.5 vs 26.6±5.9, p<0.001), had higher preconception HbA1c (5.5±0.3 vs 5.3±0.3, p <0.001), and higher first trimester HbA1c (5.6±0.5 vs 5.2±0.2, p <0.001). There were no statistically significant differences (p>0.05) between the early and standard for eclampsia, small for gestation (SGA), macrosomia, neonatal hypoglycemia, shoulder dystocia, preterm delivery, NICU admissions, neonatal respiratory distress syndrome. C-section was higher (p=0.002) in early group. Those started on medication early had higher rate of SGA (p=0.003) and neonatal hypoglycemia (p=0.01).

Conclusion: This study showed majority of women with preconception glucose intolerance undergo standard screening for GDM during pregnancy. Although no differences found in most of the maternal fetal outcomes between the groups, women started on medication early had higher SGA and neonatal hypoglycemia.

Disclosure

F. Farrokhi: None. J. Wilcox: None. C. Parise: None.
1265-P: Relationship between Oral Frailty and Sarcopenia in Older Japanese with Type 2 Diabetes
Authors: TAKAHASHI YOSHIHIRO , KUBOTA SODAI , SAKAI MAYU , KATO TAKEHIRO , TAKAO KEN , MIZUNO MASAMI , HIROTA TAKUO , HORIKAWA YUKIO , YABE DAISUKE
Published: June 2024

Introduction: Oral frailty (OF) is a condition in which oral functions are impaired. We investigated the prevalence of OF in older Japanese type 2 diabetes (T2D) and the relationship with sarcopenia.

Methods: This cross-sectional study was conducted between February and November 2023 and comprised T2D aged ≥65 years who were admitted to our hospital. At admission, we evaluated glycemic control (HbA1c), sarcopenia (skeletal muscle mass index [SMI], grip strength), and OF prevalence. Oral functions were evaluated using the checklist of the Japanese Association for Dental Science; those with three or more of seven items were diagnosed as OF.

Results: Thirty-five individuals were examined: age 75.2±5.4 years, 24 male/11 female, SMI 7.0±1.5 kg/m2, grip strength 22.1±7.6 kg, HbA1c 8.5±2.5%. Of them, 17 (48.6%) were diagnosed with sarcopenia and 30 (85.7%) with OF. When the criteria of sarcopenia and OF were delineated by gender, saliva volume (r=0.610, p=0.003) and masticatory function (r=0.566, p=0.007) were found to be positively associated with grip strength in men. In multi-regression analysis (explanatory variables: age, SMI, saliva volume, and masticatory function), saliva volume was showed a significant association (β=0.481, p=0.033) in men.

Conclusion: There is a close relationship between OF and sarcopenia in older Japanese T2D, underscoring the importance of medical-dental collaboration in diabetes care.

Disclosure

Y. Takahashi: None. S. Kubota: None. M. Sakai: None. T. Kato: None. K. Takao: None. M. Mizuno: None. T. Hirota: None. Y. Horikawa: None. D. Yabe: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd. Research Support; Terumo Corporation, Taiho Pharmaceutical Co. Ltd.
1270-P: Evolution of Stroke Incidence over 34 Years Follow-up among People with Newly Diagnosed Diabetes and Impaired Glucose Tolerance in the Da Qing Diabetes and Diabetes Prevention Study 1986–2020
Authors: AN QIER , WANG JINPING , FENG XINXING , QIAN XIN , HE SIYAO , YIN XIANG , WANG XUAN , AN YALI , ZHOU SHUHAN , LI HUI , ZHAI XIUWEI , CHEN XIAOPING , LI GUANGWEI , CHEN YANYAN
Published: June 2024

Background: Stroke is a leading cause of death among Chinese people; however, the incidence and risk attributable to stroke among adults with diabetes and pre-diabetes have not been quantified. We aimed to discover the evolution in stroke incidence among adults with diabetes and impaired glucose tolerance over a 34-year follow-up period.

Methods: We conducted an observational study among 1632 participants, including 598 individuals with newly diagnosed diabetes (NDD), 540 with impaired glucose tolerance (IGT), and 494 with normal glucose tolerance (NGT), who were initially identified in 1986 and followed up to 34 years. We compared incidence and hazard ratios for stroke across these groups and estimated the difference of median delay time of stroke onset from parametric Weibull distribution models.

Results: Over 34-year follow-up, the cumulative incidence of stroke in NDD group, IGT non-intervention group, IGT intervention group and NGT group was 65.4%, 62.8%, 49.8% and 38.2%, respectively. After adjustment for covariances, the 34 years risk of stroke was significantly higher for those in NDD, hazard ratios (HR) 1.81; 95% CI 1.47-2.72, IGT non-intervention (HR 1.63; 95% CI 1.22-2.18) and IGT intervention groups (HR 1.39; 95% CI 1.11-1.73) compared with those in NGT group. Compared with NDD, a median delay time in onset of stroke was 16.82 years (95% CI 6.50-15.57) in NGT group and 7.84 years (95% CI 4.19-11.48) in IGT intervention. Of note, the subgroup analysis in women revealed that the risk of stroke in IGT intervention group was significantly lower than those in NDD group (HR 0.64, 95% CI 0.47-0.88), and it was comparable to that in NGT controls (HR 0.99,95% CI 0.69-1.40).

Conclusions: More than half of the Chinese adults with newly diagnosed type 2 diabetes and IGT experienced a stroke over 34 years. Lifestyle interventions in women with IGT may favor the risk reduction of stroke.

Disclosure

Q. An: None. J. Wang: None. X. Feng: None. X. Qian: None. S. He: None. X. Yin: None. X. Wang: None. Y. An: None. S. Zhou: None. H. Li: None. X. Zhai: None. X. Chen: None. G. Li: None. Y. Chen: None.

Funding

Centers for Disease Control and Prevention/World Health Organization(U58/CCU424123-01-02); Chinese Academy of Medical Sciences(2020-I2M-2-006)
1271-P: Health Care Utilization and Cost with Empagliflozin vs. GLP-1RA in Patients with Type 2 Diabetes
Authors: HTOO PHYO T. , TESFAYE HELEN , WEXLER DEBORAH J. , GLYNN ROBERT , SCHMEDT NIKLAS , KOENEMAN LISETTE , PAIK JULIE M. , PATORNO ELISABETTA
Published: June 2024

Introduction & Objective: Despite the established cardiovascular benefits of empagliflozin (EMPA) and glucagon-like peptide-1 receptor agonists (GLP-1RA), questions remain on their impact on healthcare resource utilization (HCRU) and costs.

Methods: Using US Medicare fee-for-service (FFS) and Optum commercial claims (2014-19), we identified 1:1 propensity score (PS)-matched patients aged >18 years with type 2 diabetes (T2D) initiating EMPA or GLP-1RA. We estimated rate ratios (RR) and rate differences (RD) for HCRU per 1,000 person-years, and costs per member per year (PMPY) differences, overall and in patients with baseline cardiovascular disease (CVD).

Results: In 112,942 PS-matched FFS patients, EMPA was associated with similar no. of hospitalizations [RR 0.99 (0.93,1.04); RD -52 (-134, 36)], inpatient days [RR (95% CI) 0.97 (0.91, 1.02); RD -4 (-18, 10)], and no. of emergency room visits [RR 0.98 (0.94,1.01); RD -13 (-32, 6)], vs GLP-1RA. (Table). Estimates were similar in patients with CVD. Relative to GLP-1RA, EMPA was associated with lower total costs ($) [PMPY -1116 (-1359, -871)] and pharmacy costs [PMPY -800 (-934, -664)], with similar inpatient costs [PMPY 4 (-134,148)]. Findings were similar in patients with CVD. Findings from a commercial population were similar.

Conclusion: For adults with T2D, initiating EMPA versus GLP-1RA resulted in similar HCRU with lower total and pharmacy costs.

Disclosure

P.T. Htoo: None. H. Tesfaye: None. D.J. Wexler: Other Relationship; Novo Nordisk. R. Glynn: Research Support; Amarin Corporation, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. N. Schmedt: Employee; Boehringer-Ingelheim, Bayer Inc. L. Koeneman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J.M. Paik: None. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding

Brigham and Women's Hospital from Boehringer Ingelheim (116283)
1277-P: Medication Adherence Associated with Better Cardiometabolic Control among American Indians with Type 2 Diabetes
Authors: SCARTON LISA , NELSON TARAH N. , YAO YINGWEI , LEGASPI ANATOLIA , DEVAUGHAN CIRCLES ASHLEY , TURNER T. GOINS R. , SEGAL RICHARD , DONAHOO WILLIAM T. , WILKIE DIANA J.
Published: June 2024

Introduction: Increased medication adherence is expected to be associated with better health outcomes, but the extent to which medication adherence contributes to disparities in cardio-metabolic control (CMC) among American Indians is unknown. Our study purpose was to examine relationships between medication adherence and CMC in American Indians with type 2 diabetes (T2D) who live on Tribal lands with medication at no cost to them.

Methods: From Tribal electronic health record data, we obtained a cross-sectional cohort of 2,938 adults with T2D who were on all three classes of medication (anti-hypertensive, oral glucose- and lipid-lowering) in 2018. Using logistic regression models, we examined the associations between CMC and medication adherence, measured by the proportion of days covered (PDC, range 0-1).

Results: The sample mean ±SD age was 59.6±11.5 years; the majority were male (52%), married (52%), and lived in a rural setting (87%). Medication adherence for patients with a PDC of at least 80% was similar across all drug classes ranging from 63%-68% with an overall PDC of 64%. The mean for each CMC indicator was 135.6±13.2(systolic blood pressure, [SBP]), 7.8±1.6 (HbA1c), and 90.1±31.9(LDL). Higher overall PDC was associated with lower SBP (β=-12.5, p<.001), lower HbA1c levels (β=-1.8, p<.001), and lower LDL levels (β=-45.6; p<.001).

Conclusions: Our sample had higher medication adherence rates, using PDC at an 80% or higher threshold, compared to the typically estimated 40%-50% rates found in settings where medications were not provided at no cost to patients. Even with higher medication adherence rates the sample had above target CMC indicators for SBP (>130) and HbA1c (>7.0).

Disclosure

L. Scarton: None. T.N. Nelson: None. Y. Yao: None. A. Legaspi: None. A. DeVaughan Circles: None. R.T. Goins: None. R. Segal: None. W.T. Donahoo: None. D.J. Wilkie: None.
1279-P: Cumulative Exposure to High Triglyceride–to–HDL Cholesterol Ratio and Risk of Type 2 Diabetes in Young Adults
Authors: LEE MIN-KYUNG , HAN KYUNGDO , HEO JUNG , KIM BYUNGPYO
Published: June 2024

Introduction & Objective: As the prevalence of type 2 diabetes in young adults is increasing, predicting and preventing it has become a significant challenge. We aimed to evaluate whether the persistence of high triglyceride-to-HDL cholesterol (TG/HDL-C) ratio, which is a marker for insulin resistance, is associated with type 2 diabetes in young adults, considering the variability in TG/HDL-C levels over time.

Methods: This study used data from South Korea National Health Insurance Service between 2009 and 2012. A total of 1,840,251 young adults without type 2 diabetes aged 20-39 years who had undergone four consecutive annual health checkups were included. Participants were classified into five groups based on the exposure score of high TG/HDL-C ratio over a four-year period: 0, 1, 2, 3, and 4. A TG/HDL-C ratio of ≥2.8 in male and ≥1.7 in female was defined as high TG/HDL-C ratio. The risk for developing type 2 diabetes according to different exposure scores was evaluated using multivariable Cox proportional hazards regression model.

Results: During a follow-up period of 6.53 years, 40,286 (2.2%) participants developed type 2 diabetes. The cumulative incidence of type 2 diabetes significantly increased with higher TG/HDL-C ratio exposure scores (log-rank test, P < 0.001). The multivariable-adjusted hazard ratios for type 2 diabetes were 1.557 (95% CI, 1.463, 1.657), 2.046 (95% CI, 1.929, 2.171), 2.857 (95% CI, 2.707, 3.016), and 4.8 (95% CI, 4.563, 5.048) for groups with scores 1-4, respectively, compared with those with a score of 0.

Conclusion: In this large-scale prospective cohort study of young adults, cumulative exposure to high TG/HDL-C ratio was an independent risk factor for type 2 diabetes in young adults.

Disclosure

M. Lee: None. K. Han: None. J. Heo: None. B. Kim: None.

Funding

the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1F1A061069).
1292-P: Loss of Multiple Islet Autoantibody Status during Progression to Type 1 Diabetes
Authors: SIMMONS KIMBER M. , DONG FRAN , WAUGH KATHLEEN , YU LIPING , REWERS MARIAN
Published: June 2024

Introduction & Objective: Type 1 diabetes (T1D) can be diagnosed before clinical symptoms with the presence of multiple islet autoantibodies (IA) and normoglycemia - stage 1 or IA and dysglycemia - stage 2. Early-stage diagnosis allows for treatment with FDA approved teplizumab or agents being tested in clinical trials. Both options require the presence of two or more IA for eligibility; however, some individuals lose IA prior to clinical diagnosis. We explored the frequency and predictors of regression from multiple to single or negative IA status in youth who progressed to clinical T1D.

Methods: Youth with at least two IA evaluation visits prior to clinical T1D onset were included. They participated in Diabetes Autoimmunity Study in the Young (DAISY) cohort (n=90, median 14 visits/person) or Autoimmunity Screening for Kids (ASK) screening study (n=61, median 4 visits/person).

Results: Of those who progressed to clinical T1D, 92% in DAISY and 84% in ASK were multiple IA+ at least once. However, many multiple IA youth, 39% (32/83) in DAISY and 10% (5/51) in ASK, regressed to single or negative IA status prior to clinical diagnosis. The mean time from multiple to single or negative IA status was 4.0 (2.3-143.3) months. IA regression was more common in males (p=0.025), controlling for the effect of study (ASK vs DAISY). Among youth seen while in stage 2, 30% (32/106) had single or negative IA status. 54% (17/32) of progressors with single or negative IA status in stage 2 T1D had previously been multiple IA+.

Conclusions: IA levels fluctuate over time. With cross-sectional screening for T1D, many patients testing positive for a single IA may have had multiple IA historically. Current eligibility criteria for teplizumab treatment or participation in clinical trials appear too restrictive and may exclude youth who will progress to clinical T1D despite absence of multiple IA.

Disclosure

K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic. F. Dong: None. K. Waugh: None. L. Yu: None. M. Rewers: Advisory Panel; Sanofi. Other Relationship; Sanofi. Consultant; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Consultant; Provention Bio, Inc. Research Support; Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases.

Funding

National Institutes of Health (DK32493); JDRF International (3-SRA-2018-564- M-N); The Leona M. and Harry B. Helmsley Charitable Trust
1293-P: Real-World Status of Autoantibody Screening and Teplizumab Administration Readiness among Centers Participating in the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: DEMETERCO-BERGGREN CARLA , JACOBSEN LAURA M. , GUTTMANN-BAUMAN INES , OSPELT EMMA L. , SMEGO ALLISON , HANNON TAMARA S. , ALEPPO GRAZIA , CHOUDHARY ABHA , WONG JENISE C. , EBEKOZIEN OSAGIE , COLLABORATIVE T1DX-QI
Published: June 2024

Background: The interest in type 1 diabetes (T1D) screening has been ignited since the U.S. FDA approval of teplizumab (November 2022) for the delay of T1D onset among those at risk. We aimed to identify the real-world status of autoantibody screening and teplizumab administration readiness among T1DX-QI centers.

Methods: A survey was administered from July to September 2023 to 55 centers participating in the T1DX-QI. Descriptive analysis was completed.

Results: Fifty of 55 centers (91%) completed the survey; 68% were pediatric and 32% were adult centers. The majority of centers (68%) had not made any substantive changes to T1D screening practices. Of the centers that had adjusted their screening practices, most developed more specific guidelines and workflows to screen first-degree relatives of people with T1D. Pediatric centers were more prepared to administer teplizumab, with the majority developing and implementing a protocol, in comparison to adult centers (Figure 1a). There is no standard screening laboratory among adult and pediatric centers (Figure 1b).

Conclusions: It is necessary to explore the barriers to implementing T1D screening and teplizumab administration in the real-world setting as the majority of centers are still in the early stages of bringing this to clinical care.

Disclosure

C. Demeterco-Berggren: None. L.M. Jacobsen: Advisory Panel; Insulet Corporation. I. Guttmann-Bauman: None. E.L. Ospelt: None. A. Smego: None. T.S. Hannon: Advisory Panel; Eli Lilly and Company. G. Aleppo: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation. Consultant; Medscape. Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., WellDoc, Fractyl Health, Inc. Consultant; Eli Lilly and Company, Bayer Inc. Research Support; Emmes. A. Choudhary: None. J.C. Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Abbott. O. Ebekozien: Advisory Panel; Sanofi, Medtronic. Research Support; Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Research Support; Medtronic, Lilly Diabetes, Abbott, Dexcom, Inc.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust and JDRF International
1296-P: Thermal Imaging—A Simple, Rapid Device to Replace Nerve Conduction Testing for Diabetic Peripheral Neuropathy
Authors: BHATIA SOORAJ , SOLIZ PETER , SAINT-LOT SHERAZ , WIGDAHL JEFFREY , DURAN-VALDEZ ELIZABETH , SCHADE DAVID S.
Published: June 2024

Introduction & Objective: Early detection of diabetic peripheral neuropathy (DPN) in patients with diabetes mellitus can prevent amputations. However, diagnosing DPN with nerve conduction studies (NCS) is costly and requires highly trained specialists. We present a novel thermal imaging device to detect DPN via foot temperature recovery after cold provocation, which may provide enhanced DPN screening by lowering costs, facilitating nonspecialist testing, and conserving time and resources.

Methods: NCS and thermal imaging recovery data were collected from 176 patients. Plantar feet were exposed to a 2°C cooling pad for 2 min. Recovery temperature was recorded for a point on the 1st metatarsal on the right foot with a thermal video camera for 90 s. Subjects were grouped into 21 controls, 110 diabetic subjects with negative NCS testing, and 45 diabetic subjects with positive NCS testing.

Results: The figure shows the mean temperature warming following cooling with 95% confidence intervals for the 3 groups. Each curve is statistically different from the others.

Conclusion: Thermal imaging is a useful test to diagnose early DPN. It may also detect small fiber diabetic neuropathy before NCS show positive. Because NCS tests are expensive and only available in advanced clinical facilities, thermal imaging will provide greater access to DPN screening and early intervention for many diabetic patients.

Disclosure

S. Bhatia: None. P. Soliz: None. S. Saint-Lot: None. J. Wigdahl: None. E. Duran-Valdez: None. D.S. Schade: None.

Funding

National Institutes of Health (R44DK104578)
1299-P: Individualized Type 2 Diabetes Risk Prediction
Authors: JAEGER BYRON C. , WELLS BRIAN J. , STAFFORD JEANETTE M. , CASANOVA RAMON , DEMESIE YITBAREK , BANCKS MICHAEL
Published: June 2024

Introduction and Objective: Current T2D risk prediction models do not include individualized preventive intervention effects. We developed an individualized T2D prediction model with differential treatment effects based on an individual’s fasting glucose (FG) level and body mass index (BMI).

Methods: We included 2640 participants from the Diabetes Prevention Program (DPP) randomized to placebo, metformin, or lifestyle arms. Using a 50/50 train/test split, we developed and validated an individualized Cox model predicting T2D risk at 3 years (3yr) with adjustment for sex, HbA1c, triglycerides, FG, BMI, intervention, and interactions between intervention and age, FG, and BMI. We repeated this process 100 times and took the mean concordance (C)-statistic of the model. We then fit the model to all available data and calculated counterfactual T2D risk for each intervention.

Results: Mean (standard deviation) age was 51 years (11) and 54% of participants were women. The mean C-statistic was 0.78 (95% confidence interval: 0.74, 0.81). The optimal intervention (lowest 3yr risk) was lifestyle for 86% of participants and metformin for the remaining 14% (table). If assigned to lifestyle, 3yr risk was 10% for those where lifestyle was optimal and 21% when metformin was optimal. When metformin was optimal, it was associated with 44% lower T2D risk than placebo and 29% lower than lifestyle.

Conclusion: Individualized T2D risk prediction may improve preventive strategies.

Disclosure

B.C. Jaeger: None. B.J. Wells: None. J.M. Stafford: None. R. Casanova: None. Y. Demesie: None. M. Bancks: None.

Funding

American Diabetes Association (11-22-ICTSPM-18)
13-PUB: Safety and Efficacy of Tirzepatide in Patients with Solid-Organ Transplant
Authors: DOWLATSHAHI SAMANEH , PATHAM BHARGAVI , KANSARA ABHISHEK , ROGERS ALEX W. , SADHU ARCHANA R.
Published: June 2024

Objective: Preexisting diabetes mellitus (DM) and post-transplant diabetes mellitus (PTDM) impact outcomes post solid organ transplantation (SOT). Benefits of tirzepatide are well studied in DM but not in patients after SOT. This study describes safety and efficacy of tirzepatide in SOT.

Methods: Retrospective data was collected on 16 SOT patients with DM/PTDM on insulin, oral agents or both after initiation of tirzepatide for 6 months. [Table 1] Changes from baseline in A1C and weight (efficacy), and eGFR and tacrolimus levels (safety) were assessed.

Results: From baseline to 6 months, mean A1C reduced by 14.8% (-1.3%) and weight by 6.9% (-5.4 kg), but were not statistically significant. eGFR and tacrolimus levels were unchanged. [Table 2]

Conclusion: Tirzepatide may be a safe and effective drug in SOT patients. Larger studies are warranted.

Disclosure

S. Dowlatshahi: None. B. Patham: None. A. Kansara: None. A.W. Rogers: None. A.R. Sadhu: Advisory Panel; Abbott Diagnostics.
1300-P: Visceral Adipose Tissue Volume Is Increased in Severe Insulin Resistant Diabetes
Authors: ZAHARIA OANA P. , KUPRIYANOVA YULIYA , BOBROV PAVEL , SCHÖN MARTIN , MÖSER CLARA , TRINKS NINA , MENDEZ CARDENAS DANIA M. , TRENKAMP SANDRA , BÓDIS KÁLMÁN , SCHRAUWEN-HINDERLING VERA , WAGNER ROBERT , RODEN MICHAEL
Published: June 2024

Introduction & Objective: The severe insulin resistant diabetes (SIRD) endotype associates with markedly higher risk of metabolic dysfunction associated steatotic liver disease (MASLD). However, it is not known if ectopic lipid deposition is also higher in skeletal muscle or adipose tissue compartments than in other endotypes.

Methods: Participants (n=697, known diabetes duration <1 y) of the prospective German Diabetes Study (GDS) underwent 1H magnetic resonance spectroscopy for quantifying intramyocellular lipids (IMCL) in tibialis anterior muscle, intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT) volumes. The validated clustering algorithm used age, sex, BMI, HOMA-IR, HOMA-B, islet-directed autoantibodies.

Results: As expected, SIRD (n=40) had the highest IHL (11±5%) compared to mean IHL values of 2-6% in moderate obesity-related (MOD, n=215), moderate age-related (MARD, n=237) and severe autoimmune diabetes clusters (SAID, n=193; all p<0.01). Interestingly, SIRD presented with higher VAT than MOD, MARD and SAID (6089±2705 vs 3260±2310, 3056±1963, 1524±1401 cm3) even after adjustment for BMI (all p<0.05). Also, SAT was higher in SIRD than MARD (27879±6777 vs 17127±6218 cm3, p<0.05), while differences to other subtypes lost statistical significance upon correction for BMI. There were no differences in IMCL between subtypes. Overall, VAT correlated with cardiovascular risk (Framingham, r=0.661, p<0.05), whole-body insulin sensitivity derived from hyperinsulinemic euglycemic clamp (r=-0.537, p<0.05) and with beta cell function during intravenous glucose tolerance test (r=0.379, p<0.05). Within SIRD, VAT was further associated with fasting glycemia (r=0.121, p=0.05) and fasting insulin resistance (HOMA-IR; r=0.372, p<0.05).

Conclusion: The increases in IHL and VAT underline their key role in the pathophysiology and progression of severely insulin resistant diabetes and shall help to refine subtyping approaches for precision diabetology.

Disclosure

O.P. Zaharia: None. Y. Kupriyanova: None. P. Bobrov: None. M. Schön: None. C. Möser: None. N. Trinks: None. D.M. Mendez Cardenas: None. S. Trenkamp: None. K. Bódis: None. V. Schrauwen-Hinderling: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca.

Funding

EFSD Rising Star Award
1306-P: Type 2 Diabetes Screening in the 12 Months following Acute SARS-CoV-2 Infection—A Real-World Cohort Analysis
Authors: EKANAYAKE RUWANTHI N. , CHAKKALAKAL ROSETTE , ALI MOHAMMED K. , SAM VARGHESE JITHIN
Published: June 2024

Introduction & Objective: SARS-CoV-2 infection is associated with new-onset Type 2 Diabetes (T2D) and higher pandemic healthcare utilization. We evaluated Hemoglobin A1c testing rates after SARS-CoV-2 infection to explore whether new T2D diagnoses may be a consequence of increased post-infection screening.

Methods: We used data from adults (≥18 years) without diagnosed T2D from the OneFlorida+ clinical research network, who formed an Exposed cohort with a positive SARS-CoV-2 test (n = 67,343) over March 2020 - January 2022, an Unexposed cohort with negative tests (n = 206,281) over the same period, and an age-sex matched Historical cohort (n = 73,791) over March 2018 - January 2020. Using a difference-in-difference framework and stratified by race-ethnicity, we reported excess HbA1c tests in the year post-SARS-CoV-2 infection relative to the year before infection.

Results: The analytic sample was 20.5% NH Black and 22.0% Hispanic with mean age of 50.9 years (SD: 19.2). Relative to the Exposed cohort (change per 1000 individuals: 89 [95%CI: 87, 90]), the Unexposed (173 [95% CI: 171, 175]) and Historical (154 [95%CI: 143, 165]) cohorts showed larger changes in HbA1c testing. Associations were similar across racial-ethnic groups except NH Other, Figure.

Conclusion: Higher rates of diabetes screening may not explain the previously observed increased T2DM incidence following SARS-CoV-2 infection.

Disclosure

R.N. Ekanayake: None. R. Chakkalakal: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. J. Varghese: None.

Funding

National Institutes of Health (R01DK120814-05S1, P30DK111024)