bluuebunny/crossref_metadata_2025 huggingface dataset:
1088-P: Exploring Generative AI’s Clinical Potential in Type 1 Diabetes Management—An ADA Standards-Based Approach
Authors: YOUNG CLIPPER F. , WONG SHIRLEY
Published: June 2024

Objective: To compare clinical recommendations on type 1 diabetes management based on the ADA’s Standards of Medical Care - 2022 generated by two generative artificial intelligent (AI) platforms for internal consistency (vertically within a platform) and external consensus (horizontally between platforms and with clinicians’ clinical decisions).

Methods: A complex clinical case with type 1 diabetes was selected; the patient has a history of severe hypoglycemia and diabetic ketoacidosis (DKA). Before entering the case into each AI platform for analysis, the clinical note - chief complaint, subjective, and objective information - was edited and organized to enhance clarity and to standardize the language. The case was analyzed by two AI platforms three times; all AI responses were reviewed and compared to the clinician’s assessment and plan, thus taking a qualitative data analysis approach.

Results:

Conclusions: Although this initial step only included one case, both AI platforms could generate clinical recommendations with high internal consistency, especially in the effectiveness measures. For external consensus on the safety measures, ChatGPT emphasized the specific safety recommendations that aligned closer with the standards of care. Further analyses are warranted to include more cases, ensuring this approach can potentially augment clinician’s care practices in type 1 diabetes.

Disclosure

C.F. Young: Other Relationship; Abbott. S. Wong: None.
1096-P: The Diabetes On Track Model—Creating a Framework for Improving Diabetes in Rural Nebraska
Authors: EILAND LESLIE A. , MOHRING STEPHEN M. , KEEGAN SARAH , NYGAARD STEPHANIE , PULLYBLANK KRISTIN , DESOUZA CYRUS
Published: June 2024

Introduction & Objective: Outcomes for people with diabetes in rural areas are worsening, widening disparities between urban and rural populations. The objectives of Diabetes on Track are to improve outcomes for people at risk for or living with pre-diabetes and type 2 diabetes in rural Nebraska.

Methods: Investigators engaged health departments and primary care clinics in two rural communities. Community coalitions were developed with a focus on improving screening rates. Clinical interventions include a Project ECHO curriculum to disseminate evidence-based education via case-based learning, funding of RN health coach positions, and support for clinical pharmacy time. Individual provider dashboards were developed, along with a value-based incentive program tied to diabetes-related quality metrics (A1c monitoring and control; screening for dyslipidemia, nephropathy, and retinopathy). A patient pathway team aims to increase clinician awareness of community resources and improve referral workflows.

Results: Project ECHO sessions have been regularly attended with good participation. Clinics are increasing use of team-based care for people with diabetes. Over 8 months, the enhanced team approach generated 18 referrals to pharmacy, 89 to Diabetes Education, and 134 to Health Coaching. A prediabetes registry was created and thus far, 225 patients have been contacted about their risk. All diabetes-related quality metrics have improved, primarily at the site where clinicians were given visibility to the incentive program. One location has joined an ACO.

Conclusion: Improving diabetes at a community level requires a multi-pronged approach. Our model utilizes community interventions, healthcare team interventions, and a patient pathway to improve communication between health departments and local clinics. Understanding local relationships and developing trust takes time but is vital. The most impactful intervention to date has been the value-based incentive program.

Disclosure

L.A. Eiland: Advisory Panel; Provention Bio, Inc., Cecelia Health. S.M. Mohring: None. S. Keegan: Consultant; Tandem Diabetes Care, Inc. S. Nygaard: None. K. Pullyblank: None. C. Desouza: Advisory Panel; Novo Nordisk, Bayer Inc., Madrigal Pharmaceuticals, Inc. Other Relationship; ADA/ACC Diabetes by Heart Program. Advisory Panel; Asahi Kasei.

Funding

Private gift received through the University of Nebraska Foundation from the Diabetes Care Foundation.
1098-P: A Longitudinal Look at SGLT-2i/GLP-1RA Prescription Records in Evaluation of a Primary Care Quality Improvement Education Initiative
Authors: MAKIN VINNI , RAO PRATIBHA , MURRAY SUZANNE , DENNIS FRAMPTON BETHANY , LAZURE PATRICE , KAWCZAK STEVEN , PANTALONE KEVIN M.
Published: June 2024

Introduction & Objective: A longitudinal analysis was performed to evaluate a systems-based Quality Improvement Educational intervention (QIEi), designed to enhance disease management of T2D patients with/or at risk of CVD/CKD. This analysis aimed to assess if the QIEi increased SGLT-2i/GLP-1RA prescriptions for eligible patients.

Methods: The QIEi was deployed at 2 primary care sites from a USA integrated delivery system (IDS) and included baseline EHR data review to inform gaps; webinars on best practices; case-based group discussions; and team-designed process improvements and enhanced communication strategies. To assess impact, along with a practice assessment quantitative questionnaire, qualitative interviews and post-webinar quantitative assessments, EHR data were pulled and analyzed from the 2 implementation sites and IDS remaining sites at baseline and 6, 12, and 18 months.

Results: No clinically significant differences in prescription of SGLT-2i/GLP-1RA were observed post-intervention for T2D patients with/or at risk of CVD/CKD, and no differences observed between implementation and non-implementation sites (Table 1).

Conclusion: Persistent challenges in translating education into practice among HCPs needs to be identified and addressed to improve the quality of disease management for T2D patients with/or at risk of CVD/CKD.

Disclosure

V. Makin: Speaker's Bureau; Bayer Inc. P. Rao: None. S. Murray: None. B. Dennis Frampton: None. P. Lazure: None. S. Kawczak: None. K.M. Pantalone: Speaker's Bureau; AstraZeneca. Consultant; AstraZeneca. Board Member; Bayer Inc. Research Support; Bayer Inc. Speaker's Bureau; Corcept Therapeutics. Consultant; Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Research Support; Merck & Co., Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Twin Health. Consultant; Sanofi.

Funding

Eli Lilly and Company; Merck
1102-P: Quality Improvement Intervention to Improve Premeal Insulin Administration in Young Children with Type 1 Diabetes
Authors: HICKS KELLY A. , MACALUSO ERIN N.P. , KELLY SARAH R. , UYSAL SERIFE , DESALVO DANIEL
Published: June 2024

Introduction: Young children with T1D have unpredictable eating habits, which lead to post-meal insulin administration and resultant hyperglycemia. We designed a quality improvement (QI) project to promote pre-meal bolusing in young children (≤ 6 years old) with T1D.

Methods: A series of bundled Plan-Do-Study-Act (PDSA) cycles were implemented over a 1-yr period from Oct 2022-Sep 2023, including: a. Development of EMR-based parental questionnaire to assess pre-meal bolus behaviors b. Creation of a run chart in QlikView analytics platform to assess real-time progress at the population level c. Development of family-facing educational resources with strategies to enable consistent pre-meal bolusing d. Tailored education for pre-meal bolusing delivered by CDCES and RD in clinic and telemedicine encounters e. Efforts to expand CGM and automated insulin delivery system use in young children f. Psychology support for parents with fear of hypoglycemia and/or diabetes distress

Results: The rate of pre-bolusing increased by 36% over a 1-yr period from a baseline of 50% in Oct 2022 to 86% in Sep 2023 (Figure 1).

Conclusion: This QI intervention led to an increase in pre-meal bolusing in young children with T1D, which may have direct clinical benefit in optimizing glycemic outcomes (e.g., HbA1c and time-in-range). Figure 1: Control chart indicating rate of pre-meal bolusing in children ≤ 6 years

Disclosure

K.A. Hicks: None. E.N.P. Macaluso: None. S.R. Kelly: None. S. Uysal: None. D. DeSalvo: Advisory Panel; Insulet Corporation. Consultant; Dexcom, Inc.
1107-P: Reporting on the Full Clinical Implementation of the Digital Danish National PROMS Tool—Optimising Routine Diabetes Outpatient Care and Connecting Each Person with Diabetes Directly with the National IT-Infrastructure
Authors: EJSKJAER NIELS
Published: June 2024

Reporting on behalf of the VBHC-PRO-DIA Research Team.

Background: Our dedicated research team developed a national Danish digital Patient-Reported Outcome (PRO) diabetes tool to enable and advance multi-sectorial person-centered diabetes care. Now fully implemented at all 4 hospitals in our region and nationally in Denmark. 2018-2021 funded by the Danish Regions, North Denmark Region and Danish Health Data Authority.

Aim: To individualize routine diabetes care in daily practice by involving specific PwD perspectives, wishes and needs enabling targeted action plans.

Methods: Persons with diabetes (PwD) and healthcare professionals (HCP) were involved in all phases. A systematic participatory multi-stakeholder research design process with systematic involvement of +600 PwD and +40 HCP using interviews, workshops, clinical & qualitative research: 1) A minimal patient-important diabetes outcome domain set (VBHC structure). 2) A unified PRO diabetes “logic model” to use PRO to drive health value. 3) A national psychometric PRO Questionnaire & Decision-Algorithm built on nine detected domains (i.e.: treatment burden, selfcare ability, self-reported health). 4) A seamless one-click IT-tool for use of outcome data in routine diabetes care coupling the PwD and national infrastructure. 5) Datadriven implementation execution.

Results: This tool is highly accepted and shows benefits related to an active engagement of PWD focusing on person-centred individual diabetes care and adds value to the delivery of quality person-centered care.

Conclusion: We report on the full clinical national implementation of a digital scalable diabetes PROMS tool, connecting the person with diabetes, the healthcare provider and the national IT-infrastructure. Secures an individualized consultation and identifies uncovered needs and deploys action plans accordingly.

Disclosure

N. Ejskjaer: None.

Funding

Danish Regions - The North Denmark Region - Danish Health Data Authority
1108-P: Building Capacity for Diabetes Care via Endocrinology Telementoring
Authors: O'BRIEN KATELYN , SANFRATELLO NATALIE , DUNTON CATHERINE , GIULIANI ANTHONY , BRECHTELSBAUER ERIKA , STEENKAMP DEVIN W.
Published: June 2024

Introduction: An urban academic medical center initiated a project to enhance diabetes care by addressing limited in person endocrinology (endo) access. The objective was to assess the impact of a telementoring (TM) program, utilizing endo to support clinical pharmacists (CPs) managing diabetes in internal medicine (IM).

Methods: Jan-June 23, 3-6 CPs and 1 endo met virtually weekly for 1 hour to review cases that would have been otherwise referred for in person endo consult. Pre-and 3-month post A1c and BMI were collected. Endo recommendations and implementation barriers were documented in the EMR.

Results: Over 21 sessions, 41 cases were discussed. Mean baseline A1c was 9.2% and BMI was 30.3. Post-A1c or BMI was not available for 5 pts (lost to follow-up/deceased.) Mean post intervention A1c was 8.2% and BMI was 29.9. CPs universally found value in sessions and reported increased confidence in practicing diabetes care. 62 interventions were documented - most common related to med initiation or adjustment. The most common reasons for lack of implementation include pt deceased, missed follow-up, changes in insurance coverage, and frequent hospitalizations. Less than 10% of pts were subsequently referred to endo for management.

Conclusion: Building IM capacity through virtual TM support of CP driven diabetes care is feasible and results in improved 3-month glycemic outcomes and may help address limited endo access in a value based care model.

Disclosure

K. O'Brien: Advisory Panel; Bayer Inc. N. Sanfratello: None. C. Dunton: None. A. Giuliani: None. E. Brechtelsbauer: None. D.W. Steenkamp: Consultant; Abbott. Research Support; Novo Nordisk A/S, MannKind Corporation, Tandem Diabetes Care, Inc.

Funding

This activity is supported by an educational grant from Lilly (A-31212).
114-OR: Proteome-Wide Analysis of USP2 Substrates Revealed Its Role in Thermogenesis via Stabilization of EBF2
Authors: XU YUEJIE , PAN JIEMIN , HU CHENG
Published: June 2024

Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that ubiquitin-specific protease 2 (USP2), a member of the deubiquitinating enzyme family, plays regulatory roles in obesity progression. Expression of USP2 is down-regulated in the white adipose tissue of obese individuals and high-fat diet (HFD)-induced or genetically obese mice. When challenged with HFD, adipose-specific USP2 overexpression mice exhibited increased energy expenditure and thermogenic capacity, protecting mice against diet-induced obesity and the development of diabetes. In contrast, mice knocked down of USP2 expression or administered the USP2-specific inhibitor ML364 showed adverse trends regarding adipose accumulation and glucose metabolic disorders. Mechanistically, we demonstrate that, USP2 stimulate adipose thermogenesis by interacting with and deubiquitinating the transcription factor early B cell factor-2 (EBF2), which promotes thermogenic gene transcription through increasing the expression and activity of ERRα and PGC1α. Overall, our findings reveal for the first time an indispensable role of USP2 in thermogenesis and systemic homeostasis through EBF2 stabilization.

Disclosure

Y. Xu: None. J. Pan: None. C. Hu: None.
1140-P: Impact of Empagliflozin on Hyperfiltration in Youth with Type 2 Diabetes—Post Hoc Analysis of the DINAMO and DINAMO MONO Trials
Authors: BJORNSTAD PETTER , DANNE THOMAS , TAMBORLANE WILLIAM V. , KLINGENSMITH GEORGEANNA J. , SCHUELER ELKE , TARTAKOVSKY IGOR , MARQUARD JAN , ZEITLER PHILIP , WILLI STEVEN M. , LAFFEL LORI M.
Published: June 2024

Introduction & Objective: Hyperfiltration, common in youth with T2D, may increase risk for early diabetic kidney disease (DKD). The DINAMO trial showed empagliflozin (empa) vs placebo (pbo) provided durable, clinically relevant improvements in glycemic control in youth aged 10-17 years with T2D. This post hoc analysis examined changes in eGFR with empa vs pbo in the DINAMO & DINAMO MONO trials (the latter were drug naïve or not on active therapy).

Methods: We estimated eGFR using the Zappitelli combined creatinine and cystatin C equation, with hyperfiltration defined as 2 SDs above the mean for healthy youth per NHANES (>126.8 mL/min per 1.73 m2). After randomization, 116 participants received once daily empa 10 or 25 mg or pbo. We compared eGFRresponses to therapy from baseline to Week 26 stratified by hyper- and normofiltration (eGFR>126.8 and ≤126.8 mL/min per 1.73 m2, respectively), with empa dosing groups pooled.

Results: At baseline, there were 55 youth (47%) with hyperfiltration; both subgroups were of similar age and pubertal status. In the hyperfiltration subgroup at Week 26, mean eGFR had decreased substantially with empa vs pbo (Figure). In the normofiltration subgroup, mean eGFR changes between groups were similar.

Conclusion: Treatment with empa was associated with attenuated hyperfiltration in youth with T2D. The potential long-term effects of such changes on DKD risk are unclear.

Disclosure

P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. T. Danne: Speaker's Bureau; Abbott. Research Support; AstraZeneca. Consultant; Bayer Inc. Research Support; Boehringer-Ingelheim. Advisory Panel; Dexcom, Inc. Research Support; Lilly Diabetes. Advisory Panel; Roche Diabetes Care, Medtronic. Research Support; Novo Nordisk. Advisory Panel; Sanofi. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Medtronic. G.J. Klingensmith: None. E. Schueler: None. I. Tartakovsky: Employee; Boehringer-Ingelheim. J. Marquard: Employee; Boehringer-Ingelheim. P. Zeitler: Consultant; Boehringer-Ingelheim. Research Support; Eli Lilly and Company. Consultant; Eli Lilly and Company. Research Support; Janssen Pharmaceuticals, Inc. S.M. Willi: Advisory Panel; MannKind Corporation. Other Relationship; Medtronic. Advisory Panel; Boehringer-Ingelheim. Other Relationship; National Institute of Diabetes and Digestive and Kidney Diseases. L.M. Laffel: Consultant; Dexcom, Inc. Advisory Panel; Medscape, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Provention Bio, Inc., Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., MannKind Corporation.

Funding

Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance
1142-P: Fat Distribution in Youth-Onset Type 2 Diabetes
Authors: DOBBS TYLER , SHAH AMY S. , DUDLEY JONATHAN , TROUT ANDREW T. , JENKINS TODD M. , XANTHAKOS STAVRA , BROWNE LORNA , BAILEY ALEXANDER , BAUMGARTNER AMY , HINES ASHTON , RIEGLER ALLEN , RUSK SHENA , SCHAAF LISA R. , WITT KAITLYN , INGE THOMAS , HELMRATH MICHAEL , KELSEY MEGAN M. , NADEAU KRISTEN J.
Published: June 2024

Adult studies show that females generally have higher total body fat than males, with higher subcutaneous adipose tissue (SAT), yet less visceral adipose tissue (VAT), an independent risk factor for cardiovascular disease. Less is known about fat distribution in youth-onset type 2 diabetes (Y-T2D) and severe obesity (SO), specifically SAT, VAT, or the VAT/SAT ratio. Here we examine fat-specific depots by sex in participants with SO and Y-T2D enrolled in ST2OMP, a study comparing metabolic bariatric surgery (MBS) to medical treatment for Y-T2D. Abdominal MRI was performed at enrollment and volumetric analysis of SAT, VAT, and the VAT/SAT ratio was calculated. Total body fat was estimated by bioelectric impedance. Linear regression examined differences in fat distribution adjusting for specific covariates (Table). Participants (n=60) at baseline had a mean age of 16.5 yrs and BMI of 42.6 kg/m2. Females had significantly higher %body fat (51.2%) vs. males (42.1%), p <0.05. Females also exhibited lower VAT and VAT/SAT ratio compared to males, with no significant race/ethnicity differences in VAT, SAT, or VAT/SAT ratio. Youth prescribed a GLP-1 receptor agonist (RA) had lower VAT (p <0.05) and trended towards lower VAT/SAT (p = 0.07). Female youth with T2D and SO showed higher %body fat, similar SAT, but less VAT vs. males. GLP-1RA use was associated with lower VAT. Future outcomes from the ST2OMP study will examine if differences in fat distribution occur after MBS.

Disclosure

T. Dobbs: None. A.S. Shah: None. J. Dudley: None. A.T. Trout: Research Support; Siemens Healthcare Diagnostics, GE Healthcare, Perspectum Ltd. Consultant; GE Healthcare. T.M. Jenkins: None. S. Xanthakos: None. L. Browne: None. A. Bailey: None. A. Baumgartner: None. A. Hines: None. A. Riegler: None. S. Rusk: None. L.R. Schaaf: None. K. Witt: None. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. M. Helmrath: None. M.M. Kelsey: Other Relationship; Rhythm Pharmaceuticals, Inc., Lilly Diabetes. K.J. Nadeau: None.

Funding

National Institutes of Health (R01DK119450)
1144-P: Maternal Exercise Alters the Human Milk Metabolome—Associations with Infant Thermogenesis
Authors: ISGANAITIS ELVIRA M. , LU CHANG , DREYFUSS JONATHAN , KYERE-DAVIES GERTRUDE , SHORT KEVIN R. , FIELDS DAVID A. , RUDOLPH MICHAEL
Published: June 2024

Breastfeeding reduces childhood obesity risk, though the mechanisms remain unclear. We recently reported that maternal exercise significantly increases breastmilk levels of lipids and metabolites involved in brown adipocyte thermogenesis. It is unclear whether differences in these milk constituents may play a functional role in infant adipose tissue metabolism. Thus, we tested whether consumption of human milk after an acute bout of maternal exercise alters infant thermogenesis, a surrogate for brown adipose tissue function.

Exclusively breastfeeding mothers (n=31, 1-mo postpartum) completed a supervised exercise session (45 minutes, heart-rate reserve 65-75%) and, on a separate day, a control period of rest, each followed by an infant feeding session 1h afterwards. We analyzed human milk (metabolomics, lipidomics) before and after exercise. We compared infant anterior neck surface temperature (infrared thermography, IRT) following feeding of either “exercise milk” or “control milk”. We analyzed resting metabolic rate (RMR) and body composition (DXA) in all infants; a subset (n=10) also underwent fat-fraction MRI to assess sub-clavicular beige fat depot volume.

Infant temperature trended higher (+0.245°C, P=0.1) after consumption of “exercise milk” vs. “control milk”; higher delta temperature was associated with higher infant trunk fat free mass (P<0.05). Of 213 metabolites detected in breastmilk; 37 were nominally changed (P<0.05) and 3 significantly changed (FDR<0.05) by exercise. For 16 metabolites, the change in abundance with maternal exercise correlated with change in infant temperature after "exercise-" vs. "control-milk" consumption. Top-ranking positively correlated metabolites included signaling lipids, lactate, guanine, and spermine (P<0.05).

Our findings indicate that exercise-induced changes in human milk are associated with activation of infant metabolism via thermogenesis.

Disclosure

E.M. Isganaitis: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Insulet Corporation, MannKind Corporation. C. Lu: None. J. Dreyfuss: None. G. Kyere-Davies: None. K.R. Short: None. D.A. Fields: None. M. Rudolph: None.

Funding

Harold Hamm Pilot and Feasibility Grant; NIDDK P30 Pilot and Feasibility Grant
1147-P: Monogenic Obesity and Type 2 Diabetes Linked to Pathogenic DYRK1B Variants—A Comprehensive Study
Authors: JHA SUDHIR C. , KARN JYOTI P.L. , BHARTI BISHWA B. , KUMAR NAWEEN
Published: June 2024

Introduction: Dual-specificity tyrosine phosphorylation-regulated kinase 1B is implicated in metabolic processes, and its variants have been hypothesized to contribute significantly to obesity and T2D development. This study focuses on understanding the role of pathogenic, total loss-of-function variants in the DYRK1B gene in monogenic obesity and its association with Type 2 Diabetes (T2D).

Methods: A cohort of 240 individuals diagnosed with monogenic obesity and T2D was examined. Genetic sequencing was used to identify loss-of-function variants in the DYRK1B gene. Participants' metabolic profiles, including glucose and insulin levels, were monitored. Statistical analysis included logistic regression to determine the association between DYRK1B variants and disease phenotypes, and Kaplan-Meier curves were used to assess the onset of T2D in relation to obesity.

Results: Pathogenic DYRK1B variants were identified in 60% of the participants. Those with these variants presented earlier onset and higher severity of obesity and T2D compared to those without. The statistical analysis showed a significant correlation (p < 0.05) between the presence of these variants and early-onset obesity and T2D.

Conclusion: The study establishes a strong link between pathogenic, total loss-of-function variants in the DYRK1B gene and the development of monogenic obesity associated with T2D. These findings highlight the importance of genetic screening in individuals with early-onset obesity and T2D for targeted interventions. This research opens avenues for personalized treatment strategies and better management of these conditions based on genetic profiling.

Disclosure

S.C. Jha: None. J.P.L. Karn: None. B.B. Bharti: None. N. Kumar: None.
1156-P: Depression in Adolescents with Type 2 Diabetes (T2D) Attending a Multidisciplinary Tertiary Care (MTC) Clinic
Authors: TALACHUTLA SAHITYA G. , GAWEY HEIDI , GUTIERREZ-COLINA ANA , PERZOW SARAH E.D. , KELSEY MEGAN M. , SHOMAKER LAUREN B.
Published: June 2024

T2D incidence has risen ~5% per year in adolescents over the past decade. Comorbidities are common, requiring MTC that addresses medication management and lifestyle change. Clinical guidelines recommend depression monitoring, but depression in relation to health indices (e.g., HbA1c, lipids) in adolescents with T2D attending MTC is not well characterized. We aimed to evaluate depression and in-clinic psychology contact (PC) as it relates to health indices in youth with T2D presenting to MTC. Retrospective chart review of youths 12-18y with T2D was conducted for MTC visits at a pediatric hospital from 2016-21. Depression was assessed with the 20-item Center for Epidemiologic Studies-Depression Scale (CES-D). PCs were determined by charted encounters. Health indices were extracted from initial clinic visit. Fisher’s exact/Kruskal Wallis tests assessed associations of depression with PC and patient health indices. N=126 adolescents (M age±SD 15±2y) with T2D (onset age 13±3y). Majority (73%) were screened for depression in the first 2 MTC visits. Of those, 48% reported at least mildly elevated symptoms (CES-D>=16); 27% had moderately elevated symptoms (CES-D>=20). 93% (n=117) of all patients saw a clinic psychologist in the first 2 MTC visits; PC was more likely for youths with CES-D>=16 (X2=6.97, p<.01). Youths with CES-D>=20 had higher total cholesterol (212±45 vs 176±47mg/dL, p<.01) and LDL (131±43 vs 90±34 mg/dL, p<.01) than those with no-to-mild symptoms. HbA1c (9±3%) and triglycerides (253±191 mg/dL) were elevated in all patients, regardless of depression. Overall, depression screening with prompt PC is feasible in MTC for adolescents with T2D. Nearly half of youth screened had elevated depression, and youth with moderate symptoms demonstrated elevated LDL and cholesterol levels. Future work is needed to delineate the progression of depression with comorbidities, and to evaluate if early psychology contact increases likelihood of positive health outcomes.

Disclosure

S.G. Talachutla: None. H. Gawey: None. A. Gutierrez-Colina: None. S.E.D. Perzow: None. M.M. Kelsey: Other Relationship; Rhythm Pharmaceuticals, Inc., Lilly Diabetes. L.B. Shomaker: None.
1158-P: Racial Disparities in Youth with Diabetes and the COVID-19 Pandemic
Authors: MUZUMDAR UMA L. , MARCH CHRISTINE , MKPARU NKEIRUKA , LIBMAN INGRID
Published: June 2024

Racial disparities in youth with diabetes have been described with higher hemoglobin A1c (HbA1c) and lower technology use in minoritized groups. Limited data are available on the effect of the pandemic.

We assessed disparities at onset and 1 year follow-up in White and Black youth diagnosed with type 1 (T1D) and type 2 (T2D) diabetes in 2019, prior to the pandemic and 2020, 1st year of the pandemic. Of 465 subjects (49% male, 85% White), 83% were diagnosed with T1D and 17% with T2D.

At 1 year follow-up, T1D Black youth had higher HbA1c than Whites (8.9±2.5 vs 7.4±1.4, p=0.004 (onset in 2019) and 8.3±2.6 vs 7.6±1.6, p=0.1 (onset in 2020)). T2D Black youth had higher HbA1c than Whites; 9.1±2.4 vs 6.4±1.4, p=0.11 and 9.1±2.9 vs 7.7±1.5, p=0.06 for those diagnosed in 2019 and 2020 respectively, not significant likely due to small numbers. Use of continuous glucose monitors was lower in Blacks vs Whites (33.3 vs 81.9%, p=<0.001) with onset in 2019, improved in those with onset in 2020 (66 vs 77%, p=0.03).

In summary, there was a doubling in the number of youths diagnosed with T2D in 2020 compared to 2019 with Blacks presenting with higher HbA1c, more often in DKA. Higher HbA1c was seen in Blacks at follow-up irrespective of DM type or year of onset. Further research should focus on evaluating interventions before and after clinical onset of diabetes.

Disclosure

U.L. Muzumdar: None. C. March: None. N. Mkparu: None. I. Libman: None.
1161-P: Are There Sex-Differences in Response to Metabolic/Bariatric Surgery among Adolescents with Severe Obesity?
Authors: JANG SUBIN , DAHLGREN JOVANNA , JENKINS TODD M. , INGE THOMAS , RYDER JUSTIN R.
Published: June 2024

Bariatric surgery is safe and effective for adolescents, but sex-differences are difficult to examine owing to female predominance in individual studies. We pooled data from four high-quality studies to examine sex-differences among adolescent bariatric surgery. Data from three prospective observational studies and one randomized trial in the United States (Teen-LABS, FABS5+) and Sweden (AMOS, AMOS2), were harmonized. Descriptive statistics explored changes in standard body mass index (BMI) categories over time. We evaluated sex differences in % change in BMI using linear mixed effects models. 389 participants (278 females; 111 males; aged 16.9±1.5 years; 76.6% Non-Hispanic White) were used for analysis. Baseline BMI was 50.5 kg/m2 for females and 53.8 kg/m2 for males with 79.7% having gastric bypass, 16.7% sleeve gastrectomy, and 3.6% gastric banding. Severe obesity was ubiquitous among participants pre-operatively (M: 100%, F: 99.6%). At 24 months, 40%, 35%, 15%, and 6% of males, 29%, 36%, 21%, and 10% of females were in severe obesity, obesity, overweight, and normal weight categories, respectively. Mean BMI change for females and males, respectively was -22.5% and -25.5% at 6 months, -31.59% and -34.15% at 12 months, and -29.68% and -32.73% at 24 months. A greater BMI reduction was observed among males at 6 months (-2.99%, 95%CI: -5.16, -0.81%, p=0.01), 12 months (-2.56%, 95%CI: -4.52, -0.60, p=0.01), and 24 months (-3.05%, 95%CI: -6.09, -0.01, p=0.05). After adjusting for age, race/ethnicity, and types of procedure, a greater BMI reduction among males at 6 months (-1.95%, 95%CI: -3.77, -0.12, p=0.04), 12 months (-2.10%, 95%CI: -3.89, -0.31, p=0.02), and 24 months (-2.45%, 95%CI: -5.34, 0.43, p=0.10) was still observed. While weight loss following bariatric surgery is significant among both sexes up to 2 years, males consistently exhibit somewhat greater BMI reduction. The clinical relevance and mechanisms driving sex-differences warrant further exploration.

Disclosure

S. Jang: None. J. Dahlgren: None. T.M. Jenkins: None. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None.

Funding

Funding for Teen-LABS was provided by the National Institutes of Health (NIH) (U01DK072493 / UM1 DK072493 to T.H.I.) (UM1 DK095710 to C.X., T.M.J.) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH (8UL1TR000077). Support also came from National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, (UL1TR000114).
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 -< 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 (+ 2.4) years, T1D duration 5.4 years (+ 4.2), HbA1c 7.9% (+ 1.3). One-third of youth met executive dysfunction criteria (T>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<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 + 1.5 months and 80% (historical) and 61% (Pilot 4T) at 36 + 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<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