bluuebunny/crossref_metadata_2025_split huggingface dataset:
1164-P: Effect of Metformin on Gut Microbial Metabolites in Overweight and Obese Youth with Type 1 Diabetes (T1D)
Authors: FLAMMER ELIZABETH R. , GARRETT TIMOTHY J. , ISMAIL HEBA M. 
Published: June 2024

Introduction and Objective: Obesity (Ob) and insulin resistance (IR) are high in T1D and gut microbial imbalance (dysbiosis) has been linked to the development of both. Studies show that metformin partially improves IR through gut microbiome changes in type 2 diabetes. Here, we examined this metformin effect on circulating gut microbial metabolites in overweight/obese (OW/OB) youth with T1D after treatment.
Methods: Using ultra-high performance liquid chromatography tandem mass spectrometry, we analyzed serum from a placebo-controlled randomized multi-center clinical trial (NCT01881828) in 140 OW/OB youth with T1D, aged 12 -&lt; 20 yrs (mean T1D duration 7 yrs). We examined differences in metabolites after 26 weeks of treatment.
Results: Compared to placebo, we saw a significant difference in metabolites in the metformin arm, Fig 1A. Allantoic acid was lower (high levels associated with Ob and IR), while 3-indoxyl sulphate and 5-hydroxyindole were higher (low levels associated with dysbiosis and Ob), Fig 1B-D. The non-microbial metabolites carnitine, tyrosine, ornithine and citrulline were also lower in the metformin arm (high levels associated with Ob and IR).
Conclusion: In T1D, metformin therapy for 26 weeks is associated with gut microbial and non-microbial metabolite changes that have been linked to Ob and IR. This provides further insights into mechanism of metformin action.

Disclosure
E.R. Flammer: None. T.J. Garrett: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics.

Funding
NIDDK
1168-P: First-Degree Relatives with High-Risk Islet Autoantibodies Less Likely to Engage in Follow-up
Authors: O'DONNELL HOLLY K. , DONG FRAN , JOHNSON SUZANNE B. , GENO RASMUSSEN CRISTY , FROHNERT BRIGITTE I. , STECK ANDREA , BAUTISTA KIMBERLY A. , SEPULVEDA FLOR , REWERS MARIAN , SIMMONS KIMBER M. 
Published: June 2024

Background: Follow-up monitoring of islet autoantibody positive (IA+) persons is critical to early T1D identification, including prevention of diabetic ketoacidosis. We identified factors predicting completion of an initial follow-up monitoring visit after confirming high-risk IA+ (i.e., single IA+ by two methods or multiple IA+).
Methods: The Autoimmunity Screening for Kids (ASK) program screens youth aged 1-17 for IA and offers a free monitoring program if the child is identified as IA+. Multiple logistic regression was used to identify factors associated with completing the initial monitoring visit among youth identified as high-risk for progressing to T1D (i.e., single IA+ by two methods or multiple IA+).
Results: Seventy-nine percent (N=194/246) of youth completed an initial monitoring visit. Controlling for child age, sex, IA status, and race/ethnicity, youth with a first-degree relative with T1D (i.e., parent or sibling) were significantly less likely to participate in the monitoring visit (OR 0.39, p=0.04).
Conclusion: Youth at high-risk for progression to T1D with FDRs were less likely to participate in the ASK follow-up monitoring program compared to individuals without FDRs. These findings are consistent with the TEDDY study which found FDRs were less likely to complete OGTTs and food records. Potential explanations include FDRs are more confident monitoring for signs/symptoms and therefore feel the visits are less necessary. Alternatively, the burden of caring for another individual with T1D already may make follow-up for the individual identified as high-risk less feasible. Further research is needed to better understand reasons FDRs are less engaged in follow-up after being identified as high-risk for T1D. Interventions tailored to address concerns of FDRs may help increase engagement in programs monitoring high-risk IA+ children for progression to clinical T1D.

Disclosure
H.K. O'Donnell: None. F. Dong: None. S.B. Johnson: None. C. Geno Rasmussen: None. B.I. Frohnert: None. A. Steck: None. K.A. Bautista: None. F. Sepulveda: 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
National Institute of Diabetes and Digestive Kidney Disease (P30DK11607); The Helmsley Charitable Trust; Juvenile Diabetes Research Foundation
1176-P: Executive Function and Quality of Life in Youth with Type 1 Diabetes
Authors: ILKOWITZ JENIECE , STEIN CHERYL R. , POWELL SARAH , PAT GALLAGHER MARY 
Published: June 2024

Introduction & Objective: Executive function (EF) describes cognitive processes required to plan, monitor, and execute goals - skills essential to diabetes self-management. Youth with T1D (YwT1D) are at risk for weaker EF skills. Difficulties in diabetes self-management can be associated with lower quality of life (QL). We examined the relationship between EF and QL outcomes in YwT1D.
Methods: From July 2019-September 2020, we enrolled YwT1D, diagnosed for ≥6 months, ages 10-17 years, in a study measuring EF and QL. Caregivers completed the parent-report Behavior Rating Inventory of Executive Function-2 (BRIEF) and Pediatric Quality of Life Inventory (PedsQL) Diabetes Module and Family Impact Module (FIM). Higher scores on the BRIEF indicate weaker EF skills. Higher scores on the PedsQL indicate better QL and family functioning. Demographic and clinical data was collected. In linear regression models adjusted for child’s age, sex, HbA1c, and time since T1D diagnosis, we examined associations between the BRIEF’s Global Executive Composite (GEC) scale and PedsQL scales.
Results: Baseline cohort (n=50) was 54% female, race: 56% NHW, 13% NHB, 25% Hispanic, 65% privately insured, 84% used CSII, 94% used CGM; mean age (SD) 13.8 (&lt;u&gt;+&lt;/u&gt; 2.4) years, T1D duration 5.4 years (&lt;u&gt;+&lt;/u&gt; 4.2), HbA1c 7.9% (&lt;u&gt;+&lt;/u&gt; 1.3). One-third of youth met executive dysfunction criteria (T&gt;65 on any BRIEF subscale). In adjusted models, each SD increase on the GEC was associated with a 6-point (95% CI -10.2, -1.9) decrease in the PedsQL Diabetes Module, an 11.2-point (95% CI -15.7, -6.6) decrease in FIM, and a 9.7% (95% CI -15.9, -3.6) decrease in CGM wear time.
Conclusion: Among YwT1D, weaker EF skills were associated with decreased diabetes-specific QL and increased impact on family functioning. Proactive surveillance and support for EF deficits in T1D self-management education may improve health-related QL and family functioning. Future research is needed to determine if integrating neuropsychology services with T1D education improves QL and glycemic outcomes.

Disclosure
J. Ilkowitz: None. C.R. Stein: None. S. Powell: None. M. Gallagher: None.
1182-P: GLP-1 Agonist Therapy in Adolescents and Young Adults with Type 1 Diabetes
Authors: SHACHAM NITSAN , ILKOWITZ JENIECE , STEIN CHERYL R. , PAT GALLAGHER MARY 
Published: June 2024

Introduction & Objective:GLP-1 agonist (GLP-1) therapy improves metabolic measures (MetM) in youth with type 2 diabetes. Little is known about the effects of GLP-1 use in adolescents and young adults (AYA) with type 1 diabetes (T1D). Our objective was to determine whether GLP-1 therapy improved MetM in AYA with T1D and elevated BMI.
Methods: We conducted a retrospective chart review of all AYA with T1D prescribed a GLP-1 over a 2-year period (2021-23) at our center. Nine of 16 AYAs with T1D and elevated BMI prescribed a GLP-1 had started treatment. Demographic and clinical information were recorded at baseline and the most recent visits. The % change from baseline for each MetM was calculated for each AYA individually and the group.
Results: GLP-1s used included liraglutide, semaglutide, and tirzepatide. Baseline cohort (n=9) was 66.7% female, race: 7 NHW, 1 NHB, 1 multiracial, 78% privately insured, 100% used CSII and CGM; median (IQR) age 17.8 years (15.5, 20.3), T1D duration 10.9 years (9,11), HbA1c 7.3% (7.2, 8.4), BMI 30.3 kg/m2 (28.6, 31.7), and weight 81.1 kg, (77.3, 90.8). Median treatment time was 10 months (6, 12). GLP-1s were well tolerated (33% GI complaints) and most AYAs had improved MetM across all domains (Figure 1).
Conclusion: GLP-1 use among AYA with T1D was well-tolerated and associated with improved metabolic measures in a real-world setting. Randomized controlled trials assessing long-term clinical efficacy are warranted.

Disclosure
N. Shacham: None. J. Ilkowitz: None. C.R. Stein: None. M. Gallagher: None.
1185-P: Sex-Related Differences in Sleep Disruptors in Adolescents with Type 1 Diabetes (T1D)
Authors: TAYLOR KASSERINE , GENO RASMUSSEN CRISTY , FIVEKILLER EMILY , JASER SARAH S. , MELTZER LISA J. , PAUL WADWA R. , COBRY ERIN C. 
Published: June 2024

Quality sleep is essential for physical and mental health, diabetes self-management, and school performance for adolescents with T1D. Social, environmental, and health-related factors are known to impact sleep quality, but few studies have examined sex-related differences in this population. These adolescents face unique challenges not quantifiable with existing surveys, lending importance to firsthand accounts through qualitative methods. We examined differences in barriers to sleep among biologic sexes in adolescents aged 11-17 years with T1D.
Adolescents (n=32, age 14.5±2.0 years, T1D duration 5.8±3.3 years, A1c 7.2±0.8%, 63% biologic female, 75% non-Hispanic White) participated in semi-structured qualitative interviews to explore the impact of sex on sleep disruptors. Interviews were recorded, transcribed, and thematically coded by two trained staff for interrater reliability.
Both sexes reported negative impacts on mood, lack of motivation, and poor performance during the day when experiencing poor sleep. Social interaction, activities/sports, diabetes management and devices, school, and electronics were equally prominent barriers to quality sleep between males and females, whereas females were more likely to report insufficient sleep due to anxiety and peer-related stress. Females also reported a greater concern of nocturnal hypoglycemia and reported more actively treating hypoglycemia before bed. Both males and females reported a high level of parental diabetes management during the night, reducing diabetes-specific disruptions for the adolescent. However, they felt this resulted in desensitization to nocturnal alarms.
Adolescents with T1D face many shared barriers to quality and sufficient sleep. Notably, in this cohort, social disruptors to sleep, anxiety, and fear of hypoglycemia appeared to impact females more than males. Further exploration is needed to evaluate observed sex-specific barriers to sleep and tailor interventions to address these barriers.

Disclosure
K. Taylor: None. C. Geno Rasmussen: None. E. Fivekiller: None. S.S. Jaser: None. L.J. Meltzer: Consultant; Egetis Therapeutics, Harmony Biosciences, Zepp Health. R. Wadwa: Research Support; Dexcom, Inc. Other Relationship; Dexcom, Inc. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company, Provention Bio, Inc. Research Support; Tandem Diabetes Care, Inc. Other Relationship; Eli Lilly and Company. E.C. Cobry: Advisory Panel; Dexcom, Inc. Other Relationship; Dexcom, Inc.

Funding
JDRF (5-ECR-2022-1179-A-N)
1188-P: Sustained Improvements in Glycemia over Three Years in the Teamwork, Targets, Technology, and Tight Control (Pilot 4T) Study
Authors: PRAHALAD PRIYA , DING VICTORIA , ZAHARIEVA DESSI P. , ADDALA ANANTA , BISHOP FRANZISKA K. , FOX EMILY , GUESTRIN CARLOS , HOOD KOREY K. , JOHARI RAMESH , SCHEINKER DAVID , DESAI MANISHA , MAAHS DAVID M. , STUDY GROUP 4T 
Published: June 2024

In the Pilot 4T Study (diagnosed 2018-2020), youth with new onset T1D were started on CGM in the first month of diagnosis, had tight glucose targets (A1c&lt;7.5%, 2018 ADA target) and received remote patient monitoring (RPM). Youth had a 0.5% A1c reduction compared to historical controls (diagnosed 2014-2016) at 12 months post-diagnosis. We hypothesized that A1c would remain lower in the Pilot 4T cohort vs. the historical cohort over three years.
A1c data were available for 88% (historical) and 75% (Pilot 4T) at 24 &lt;u&gt;+&lt;/u&gt; 1.5 months and 80% (historical) and 61% (Pilot 4T) at 36 &lt;u&gt;+&lt;/u&gt; 1.5 months post-diagnosis. Population-based A1c trajectories over three years in the historical and Pilot 4T were visualized using locally estimated scatter plot smoothing (LOESS; Fig 1). Mean A1c at diagnosis was higher in Pilot 4T (12.3±2.1%) than in the historical cohort (10.9±2.5%). At 18, 24, 30, and 36 months post-diagnosis, the Pilot 4T cohort had LOESS-based mean A1c of 0.72, 0.78, 0.95, and 1.09 percentage points lower than the historical cohort.
Fewer A1c data points were available in the Pilot 4T cohort, likely due to increased telehealth during the COVID-19 pandemic. The 4T program (teamwork, tight glucose targets, early CGM initiation with RPM) was associated with lower A1c during the first 36 months post-diagnosis compared to historic interventions, further supporting 4T adoption in all youth with new onset T1D.

Disclosure
P. Prahalad: None. V. Ding: None. D.P. Zaharieva: Research Support; Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Dexcom, Inc. Research Support; Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Research Support; International Society for Pediatric and Adolescent Diabetes. Board Member; Juvenile Diabetes Research Foundation (JDRF). A. Addala: None. F.K. Bishop: None. E. Fox: None. C. Guestrin: None. K.K. Hood: Consultant; Cecelia Health, Sanofi. R. Johari: None. D. Scheinker: None. M. Desai: None. D.M. Maahs: Advisory Panel; Medtronic. Consultant; Abbott, LifeScan Diabetes Institute, Sanofi, Provention Bio, Inc., Bayer Inc., Kriya Therapeutics, BioSpex.

Funding
NIDDK (R18DK122422); Helmsley Charitable Trust (G-2002-04251- 2); ISPAD-JDRF Research FellowshipSDRC (1P30DK 11607401); LPCH Auxiliaries National Science Foundation (2205084); Stanford HAI Stanford Maternal & Child Health Research Institute CTSA U (UL1TR003142); StanfordáREDCapáPlatformá(UL1 T001085)
1190-P: Elevated Serum IgA is Associated with Relatively Preserved Stool Microbiome at the Onset of Pediatric Type 1 Diabetes (T1D)
Authors: THAKKAR AMRUTA , HOFFMAN KRISTI L. , HAJJAR JOUD , CORMIER JUWAN , AHMED MAAZ , MINARD CHARLES G. , ISMAIL HEBA M. , PETROSINO JOSEPH , REDONDO MARIA J. 
Published: June 2024

Introduction & Objective: People with or at risk for T1D have decreased stool microbiome diversity. Secretory IgA modifies and is modified by the gut microbiota, but the role of serum IgA is less understood. Serum IgA is nonetheless elevated in 20% of children with T1D. We aimed to determine whether elevated serum IgA levels are associated with altered gut microbiome characteristics at the onset of pediatric T1D.
Methods: We prospectively enrolled children (2-18 years old) diagnosed with T1D within the past 6 months with age-adjusted serum IgA levels in the normal range (T1D-NL-IgA, n=18) or elevated (T1D-HI-IgA, n=14) and nondiabetic children, including siblings (NoDM, n=15). Using a single stool sample from each participant, we performed 16Sv4 rRNA gene sequencing and characterized the gut microbiome with respect to IgA status and other clinical measures. Microbiome alpha and beta diversity were tested via linear regression and Permutational Analysis of Variance (PERMANOVA), respectively, while differences in taxa were determined by Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC). All microbiome analyses were adjusted for age, race, and sex.
Results: The T1D-HI-IgA group, compared to T1D-NL-IgA, had significantly lower BMI percentile (25% vs 48%, p=0.042) and higher HbA1c (mean 13.2% vs 11.1%, p&lt;0.001) but similar glucose levels (p=0.41) at onset. Alpha diversity decreased with higher glucose (Observed OTUs: p=0.093; Inverse Simpson: p=0.007) but not with C-peptide. The T1D-NL-IgA group had the lowest bacterial richness (p=0.009 vs NoDM, p=0.048 vs T1D-HI-IgA) and greater differences in relative abundance of core taxa, including lower levels of Sutterella, Prevotella-9, and Akkermansia, and higher levels of Agathobacter, Lachnospira, and Parasutterella.
Conclusion: Our results suggest that elevated serum IgA at onset of pediatric T1D may mark a longer, slower preclinical stage, with a more preserved gut microbiome profile.

Disclosure
A. Thakkar: None. K.L. Hoffman: None. J. Hajjar: Research Support; Takeda Pharmaceutical Company Limited. Advisory Panel; Pharming. Speaker's Bureau; Pharming. Board Member; Immune Deficiency Foundation. Research Support; Immune Deficiency Foundation, Jeffrey Modell Foundation. J. Cormier: None. M. Ahmed: None. C.G. Minard: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. J. Petrosino: None. M.J. Redondo: None.

Funding
Texas Children's Hospital/Baylor College of Medicine Pediatric Diabetes and Endocrinology Research Center
1191-P: Glycemia Does Not Vary in Proximity to Self-Reported Menstrual Cycles in Adolescents with Type 1 Diabetes
Authors: MCDONOUGH RYAN , PRIEBE ANNE-MARIE , HILYARD TENNILLE , DILEEPAN KAVITHA , TSAI SARAH 
Published: June 2024

Introduction & Objectives: Menstruation can change the glycemia and insulin needs of individuals living with T1D. Hormonally-induced insulin resistance is thought to play a role in this process. This study evaluates if current treatment methods are associated with differences in CGM-recorded glycemia in relation to the timing of reported last menstrual periods (LMP).
Methods: Adolescent girls with T1D aged 10-18 years connected to a Midwestern Pediatric Diabetes Center Clarity account, were eligible for inclusion. A standard review of systems, which includes a reported LMP, is administered to all ambulatory patients across the organization. All patients reporting any LMP from 11/2018 - 8/2023 were included. CGM data was extracted from Dexcom Clarity and analyzed relative to the date of the LMP.
Results: During the study, 689 unique patients reported a total of 1892 menstrual cycles. Ambulatory Glucose Profile metrics were compared for the 7 days before and 7 days after the start of the self-reported LMP. There were no statistically significant differences in any of the CGM metrics (Table 1).
Conclusions: In this retrospective study, CGM metrics were not statistically or clinically different in the 7 days before to and the 7 days after a self-reported LMP. Prospective future studies are needed to evaluate the effects of advanced insulin delivery systems on glycemia in proximity to menstrual cycles.

Disclosure
R. McDonough: Speaker's Bureau; Provention Bio, Inc. A. Priebe: None. T. Hilyard: None. K. Dileepan: None. S. Tsai: Stock/Shareholder; Dexcom, Inc.
1192-P: Implementation-Effectiveness Trial of a Mindfulness-Based Intervention with Diabetes Education in Adolescents with Type 1 Diabetes
Authors: RAY LAUREN A. , PIKE JULIE M. , MACHUCA LUZ A. , ECKERT GEORGE J. , BRODERICK PATRICIA C. , HANNON TAMARA S. 
Published: June 2024

Diabetes control and self-efficacy are related, particularly in adolescents. Mindfulness-based interventions (MBI) are associated with improved mental health outcomes. Our objective was to evaluate acceptability and clinical outcomes of a MBI in adolescents with T1D. We performed a 2-arm implementation-effectiveness trial in adolescents 15-17y with T1D diagnosed for &lt;u&gt;&gt;&lt;/u&gt;6 mo. Participants received the evidence-based Learning to BREATHE MBI with diabetes education (MBI+DE) or DE only (DE). DE focused on topics for transitioning to adulthood. For each arm, 12 virtual group sessions were held weekly. Feasibility and acceptability were assessed by enrollment, attendance, and survey completion. Secondary outcomes included HbA1c at appointments and mental health questionnaires. Analyses included independent samples t-test and repeated measures. Sixty adolescents were recruited and 29 enrolled (MBI+DE=20, DE=19, 52% female). Pre (8.3&lt;u&gt;+&lt;/u&gt;0.4%) and post-HbA1c (8.3&lt;u&gt;+&lt;/u&gt;0.3%) were similar. Session attendance was 7.2&lt;u&gt;+&lt;/u&gt;3.3 for MBI+DE and 7.9&lt;u&gt;+&lt;/u&gt;3.1 for DE (p=0.57) and 62% completed both survey sets. All reported managing &lt;u&gt;&gt;&lt;/u&gt;1 area of life better after the study and 70% reported improved coping with stress. All MBI+DE participants reported practicing &lt;u&gt;&gt;&lt;/u&gt;1 MBI skill outside of group sessions. While similar at baseline, MBI+DE reported better coping with stress (3.9&lt;u&gt;+&lt;/u&gt;0.6; 6-point Likert scale) compared to DE (3.3&lt;u&gt;+&lt;/u&gt;0.5, p=0.03) post-intervention. DE demonstrated a trend for improved scores on the Problem Areas in Diabetes-Teen questionnaire (DE pre 76&lt;u&gt;+&lt;/u&gt;12, post 53&lt;u&gt;+&lt;/u&gt;8, p=0.06; MBI+DE pre 63&lt;u&gt;+&lt;/u&gt;7, post 66&lt;u&gt;+&lt;/u&gt;7, p=0.60). In adolescents with T1D, implementation of a MBI is acceptable and associated with improved coping skills. MBI with ongoing diabetes education may improve self-efficacy and coping with T1D. It is yet to be seen whether MBI results in long-term impact on diabetes outcomes.

Disclosure
L.A. Ray: None. J.M. Pike: None. L.A. Machuca: None. G.J. Eckert: None. P.C. Broderick: None. T.S. Hannon: Advisory Panel; Eli Lilly and Company.

Funding
Indiana Clinical and Translational Sciences Institute funded in part by National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (UL1TR002529)
1193-P: Patterns of Autoimmunity in Youth with New-Onset Diabetes Mellitus during the COVID Era
Authors: MONTGOMERY EMILY L. , WINTERGERST KUPPER A. , WATSON SARA 
Published: June 2024

Introduction: The incidence of diabetes mellitus increased globally during the COVID pandemic with changes in autoimmunity patterns reported in Europe. We sought to evaluate these patterns in our US-based patient population.
Methods: Retrospective chart review of patients 1-21 years of age diagnosed with type 1 diabetes at our institution. Patients diagnosed between 1.2017-2.2020 were categorized as pre-pandemic and those diagnosed between 3.2020-12.2022 as pandemic. Chi-square analysis was used to evaluate the difference in autoantibody patterns between these periods.
Results: During the pandemic, 385 patients were diagnosed with T1DM compared with 377 patients in the pre-pandemic period. Compared to the pre-pandemic period, the proportion of patients with positive for IA2A during the pandemic decreased from 72.5% to 63.9% (p &lt;0.001) with associated decrease in GAD+IA2+ from 40.3% to 34.2% (p&lt;0.001), increase in GAD+ only from 12.7% to 18.0% (p = 0.002) and increase in GAD+IAA+ from 4.2% to 6.6% (p=0.019). During the pandemic, the frequency of patients with autoimmune thyroiditis decreased from 17.8% to 13.9% (p=0.045) and the frequency of patients with positive celiac screen increased from 6.0% to 10.1% (p&lt;0.001).
Conclusion: Our study demonstrates a shift in autoimmunity pattern, in a US population that persisted through 2022, with a decrease in IA2 positivity and autoimmune thyroid disease at presentation. Further investigation to evaluate for drivers of this change is important to improve understanding of the risk of comorbidities, particularly in those diagnosed since the onset of the COVID pandemic.

Disclosure
E.L. Montgomery: None. K.A. Wintergerst: None. S. Watson: None.