bluuebunny/crossref_metadata_2025_split huggingface dataset:
1165-P: Untangling the Interactions of Glycemic Control and Obesity on Hypothalamic Gliosis in Youth with Type 1 Diabetes
Authors: HUANG ALYSSA , MELHORN SUSAN J. , EITEL KELSEY B. , PIHOKER CATHERINE , SCHUR ELLEN 
Published: June 2024

Introduction and Objective: Adolescents and young adults (AYA) with T1D experience high rates of disordered eating behavior (DEB), and obesity, which are linked to worse health outcomes including glycemic control. Inflammatory changes in the brain such as gliosis specifically in the mediobasal hypothalamus (MBH) -a critical area for weight regulation- may contribute. Adults with T2D have greater MBH gliosis compared to those with impaired glucose tolerance or normoglycemia, independent of adiposity. We investigated the presence of MBH gliosis in AYA with T1D and assessed its association with adiposity and glycemic control.
Methods: We recruited females aged 15-25 years; 24 with T1D and 5 healthy controls. AYA with T1D had stable insulin regimens and had diabetes duration for at least 1 year. Those with history of serious chronic conditions, eating disorder, extreme fluctuations in weight or glycemic control were excluded. Participants completed fasting labs, DEB surveys, DEXA scan and multi-echo brain MRI. T2 relaxation time (a measure for gliosis) was quantified in the MBH and control regions: amygdala (AMY) and putamen (PUT). Linear regression tested if T2 relaxation time in brain regions of interest were associated with body mass index (BMI) and HbA1c.
Results: For those with T1D, diabetes duration was 8.9±2.8 y and mean HbA1c was 7.9 ±1.7% (range 5.7 to 11.8%). 10 were lean and 14 had overweight or obesity based on BMI. There was a positive trend between MBH T2 relaxation time and BMI but not for other brain regions (MBH p=0.12; R = 0.28; AMY p=0.26, R=0.22; PUT p=0.30, R=0.2). There was no association between HbA1c and T2 relaxation in all brain regions (MBH p=0.88, R=0.3; AMY p=0.79, R= 0.05; PUT p=0.93, R=0.01).
Conclusion: We observed a trend that suggests that BMI but not HbA1c may be associated with MBH gliosis in AYA with T1D. Although glycemic control is associated with MBH gliosis in adults with T2D or insulin resistance, this relationship may not be present in AYA with T1D.

Disclosure
A. Huang: None. S.J. Melhorn: None. K.B. Eitel: None. C. Pihoker: None. E. Schur: Consultant; Amgen Inc.

Funding
UW Diabetes Research Center Pilot and Feasibility Award (P30DK017047-45S2)
1170-P: Comparative Measurement Utility of Diabetes Distress (DD) Surveys in Adolescents and Young Adults (AYA) with Type 1 Diabetes (T1D)
Authors: WENTZELL KATHERINE , ALAMARIE SELMA A. , HERNDON CHRISTOPHER , TINSLEY LIANE J. , LAFFEL LORI M. , HOOD KOREY K. 
Published: June 2024

Introduction: The AYA developmental period is marked by higher A1c values and higher levels of DD. To better understand how to best measure DD in AYAs, we compared 3 diabetes-related emotional distress scales.
Methods: In a multi-site project, we collected sociodemographic, clinical, and DD measures in a cross-sectional sample of 14-25 year olds with T1D ≥1 year and eligibility A1c 7-13%. DD measures included the 2 most widely used, PAID-Peds and DDS, and our new measure, PAID-EA (Table). We assessed internal consistency, reliability, and construct validity. Pearson correlations, t-tests, and ANOVAs determined the strength and direction of relationships.
Results: In 191 participants, mean (±SD) age was 19.8±3.4, T1D duration 11.4±5.4, and A1c 8.0±1.2%; 98% used CGM, 86% used an insulin pump. In this sample, Cronbach alpha was acceptable for all measures, showing internal consistency. Evidence of construct validity was observed as measures were all correlated. Females reported more DD than males on all measures. DD did not differ by health insurance status. Young adults (19-25) reported more DD compared with teens (14-18) on all measures, but the PAID-EA and DDS were the only scales positively correlated with A1c in 19-25 age group.
Conclusion: PAID-Peds, PAID-EA, and DDS performed well in AYAs. The PAID-EA and DDS were more closely tied to A1c in young adults, and thus may be preferable.

Disclosure
K. Wentzell: None. S.A. Alamarie: None. C. Herndon: None. L.J. Tinsley: None. 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. K.K. Hood: Consultant; Cecelia Health, Sanofi.

Funding
NIH (R01DK129479); Mary K. Iacocca Foundation
1172-P: Evaluating Factors that Predict Time Spent in Automated Mode (AM) among Youth with Type 1 Diabetes Using AID
Authors: GRUNDMAN JODY , LONGENDYKE RACHEL L. , PERKINS AMANDA G. , MONAGHAN MAUREEN , STREISAND RANDI , MAJIDI SHIDEH 
Published: June 2024

Introduction: Demographic and medical factors influencing AID AM use were evaluated to better understand inequities in glycemic outcomes among youth with T1D.
Methods: Retrospective chart review was conducted for 74 youth with T1D who started AID between 12/1/2022 to 5/31/2023 to examine time spent in AM 0-3 and 3-6 months after AID initiation. Mixed effects models assessed age, T1D duration, sex, race/ethnicity, insurance, AID system and input, and CGM metrics’ impact on time spent in AM. X2 and Mann Whitney U tests assessed for differences between youth with optimal (&lt;u&gt;&gt;&lt;/u&gt;90%) and suboptimal (&lt;90%) time spent in AM.
Results: Demographic and glycemic characteristics are described in Table 1. Race/ethnicity differed significantly among optimal and suboptimal AID use with NHB youth more likely to have suboptimal use (3mo p&lt;.05, 6mo&lt;0.001). Youth with optimal AID use had better glycemic outcomes at 3 and 6 months versus suboptimal use. Mixed effects models demonstrated that AID system type (p&lt;.05) was predictive of optimal AM use at 3 months. Younger age at pump start, longer duration of T1D, more boluses/day, and higher % CGM wear time (all p’s &lt;.05) were associated with higher AID use at 6 months.
Conclusions: Youth with optimal AID use had significantly better glycemic outcomes. Efforts to address individual level AID use and barriers can help to promote optimal AM use and improve health outcomes for all youth living with T1D.

Disclosure
J. Grundman: Research Support; Dexcom, Inc. R.L. Longendyke: None. A.G. Perkins: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc. M. Monaghan: Employee; National Institute of Diabetes and Digestive and Kidney Diseases. R. Streisand: None. S. Majidi: Other Relationship; Sanofi.
118-OR: The Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to That of Lean Controls
Authors: WANG YAN , YAN SHIJUN , BANICKI MATTHEW , COCHRAN MARY , PORTILLO CLAUDIA , GUERRERO GABRIEL , PAN YONG , COWDIN SAMANTHA , PATIL CHRISTOPHER , REBO JUSTIN , HUGHES ROBERT , MONTGOMERY RUSTY , MORGEN ERIC , FORTNEY KRISTEN , RUBIN PAUL 
Published: June 2024

Introduction & Objective: Incretin receptor agonists have emerged as leading treatments for obesity. Despite the efficacy of these drugs, they can negatively impact body composition, raising interest in complementary mechanisms. In a Phase 1b trial, our oral apelin receptor agonist azelaprag preserved muscle mass, quality, and protein synthesis during bed rest and shifted the plasma proteome into a state associated with endurance exercise, including higher basal metabolic rate and VO2 max. Accordingly, we tested whether azelaprag could improve body composition and muscle function in mice on incretin agonist therapy.
Methods: High fat diet-induced obese (DIO) mice were treated for 20 days with incretin agonists, with or without azelaprag. Food and water intake, serum glucose and protein levels, body composition (via EchoMRI), and grid hang latency were measured.
Results: DIO mice on tirzepatide (10 nmol/kg) lost 16% of body weight, while mice on tirzepatide+azelaprag (1.1 g/L) lost 39%, bringing body weight in range of lean controls. Combined treatment also improved body composition: DIO/tirzepatide mice had lean mass 60% of body weight, vs. 69% for DIO/tirzepatide+azelaprag and 70% for lean controls. Grid hang assays showed that azelaprag fully restored muscle function to that of lean controls (latency, 79 sec): DIO/tirzepatide, 38 sec; DIO/tirzepatide+azelaprag, 86 sec. Similar results were obtained with semaglutide.
Conclusion: Addition of azelaprag to incretin regimens increased weight loss while restoring body composition and muscle function relative to monotherapy. In the clinic, combination therapy has the potential to amplify healthy weight loss, enabling next-generation oral incretin drugs to achieve efficacy comparable to current injectables with improved tolerability.

Disclosure
Y. Wang: None. S. Yan: None. M. Banicki: None. M. Cochran: None. C. Portillo: None. G. Guerrero: None. Y. Pan: None. S. Cowdin: None. C. Patil: None. J. Rebo: None. R. Hughes: None. R. Montgomery: None. E. Morgen: None. K. Fortney: None. P. Rubin: None.
12-PUB: Tirzepatide—Efficacy, Safety, and Satisfaction in Real World Type 2 Diabetes Application in Japan
Authors: KANEKO SHIZUKA , ASAI YUKI , NAKAZAKI AYA , ITO SAYA , HIROBATA TOMONAO 
Published: June 2024

To analyze the efficacy and safety of Tirzepatide (Tir) in improving blood glucose control in clinical practice. People with type 2 diabetes who received Tir for 8 months from April 2023, were retrospectively evaluated for changes in HbA1c and given a satisfaction survey. Of the 94 people (49 males, age 63±15 years, BMI 25.3±6.7, starting HbA1c 8.1±1.7 %, 25 people on insulin), 2 were on Tir 10 mg, 3 on 7.5 mg, and the rest on ≤5 mg. HbA1c decreased on average 1.7±1.7 % and 8 were weaned from insulin therapy. Eight had no change in HbA1c or a worsening of around 0.55% on average due to oral medications or insulin dose reductions. Ten ceased Tir therapy, 3 of which achieved effective target HbA1c and were weaned at their request, 1 had large weight loss, 1 experienced hypoglycemia due to combined use with insulin and preferred to discontinue Tir rather than reduce insulin dosage, 5 experienced gastrointestinal symptoms, and 1 changed to a GLP1 formulation due to infrequent hospital visits. In one case, sleep apnea improved, and one person with Alzheimer's disease and uncontrolled food intake achieved a healthy level of food intake. One person with Prader-Willi syndrome could not reach target HbA1c due to dietary restriction limitations caused by possible insufficient Tir dosage. In the survey, 80% were satisfied, 50% would recommend the treatment to others due to superior overall results and weight loss, and 50 % stipulated unwillingness in recommending it to others, although satisfied, due to uncertainty over the effectiveness in others. Two percent were dissatisfied. Eighty percent of respondents indicated continued treatment. In comparison to their previous therapies, 90% felt healthier and more active, that Tir was a better fit and didn't place a burden on their daily lives, and that it was successful in controlling body weight. Further observation is needed.

Disclosure
S. Kaneko: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Speaker's Bureau; Novartis AG, Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical, Bayer Inc., Boehringer-Ingelheim. Y. Asai: Speaker's Bureau; Kowa Company, Ltd. A. Nakazaki: None. S. Ito: None. T. Hirobata: Speaker's Bureau; Kowa Company, Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Novartis AG, Otsuka Pharmaceutical, Boehringer-Ingelheim.

Funding
The Cookie Testing Study Group
1204-P: Challenges to Optimal Outcome during Automated Insulin Delivery (AID) Use in High Risk Youth
Authors: MCCONAUGHEY BRANTLEE , CHALEW STUART 
Published: June 2024

Introduction: Youth with type 1 diabetes (T1D) often do not achieve A1c target. This is especially problematic among Non-Hispanic Black (NHB) patients who may have less access to advanced technologies. To gain insight into ways to mitigate the disparity in glycemic outcome for high risk patients, we conducted a field trial of AID use among NHB youth with suboptimal A1c.
Methods: Self-identified NHB youth with T1D, aged 10-17, A1c 8-10%, ≥2 clinic visits in past year, no DKA for 6 mon, naive to AID, willing parent, access to video conferencing were invited to participate. Participants (pts) were instructed in use of Medtronic 670G Advanced Hybrid Closed Loop pump, by a CDCES nurse. The same nurse maintained at least once a week contact/support with the family for the first 4 wks. Thereafter, pts could elect to continue AID, plus have 1-on-1 enhanced availability of nurse support as needed/desired via video conference, phone or in person for another 5 mon, in addition to clinic follow up at 3 and 6 mon. The same nurse would initiate contact at least once a month if no contact had been made by the family.
Results: A total of 8 pts initially enrolled. One pt dropped out in the first wk. Remaining pts successfully initiated AID and agreed to continue beyond the first mon. One pt was discontinued after 3 mon due to inability to utilize AID safely. Three pts achieved lower A1c, 2 having A1c&lt;8. While 4 pts had higher A1c compared to pre-AID. Overall group A1c and MBG during AID were similar to baseline. Factors potentially contributing to lack of improvement were reluctance to initiate/seek nurse contact, missing meal boluses, difficulty keeping system in automated mode.
Conclusions: Most pts preferred AID to prior insulin delivery mode and safely used it. However, access to AID and increased availability of staff support were not sufficient to improve overall glycemic control for this group. Innovations to increase pt support and facilitate AID use appear necessary to optimize glycemic outcome for high risk patients.

Disclosure
B. McConaughey: None. S. Chalew: None.
1210-P: Maternal Diets Enriched in Olive Oil Prevent Altered Regulation of mTOR Pathways in the Decidua of the Prepubertal Offspring of Diabetic Rats
Authors: GATTI CINTIA R. , SCHIBERT FLORENCIA J. , LEONARDI MARÍA L. , HIGA ROMINA , JAWERBAUM ALICIA 
Published: June 2024

Introduction & Objective: Maternal diabetes can program offspring´s diseases. mTOR pathway is crucial in decidualization, needed for properly early embryo development. In a rat model of pregestational diabetes, the female offspring showed reduced decidual levels of microRNA-21 (miR21), a microRNA involved in decidualization, an alteration prevented by a maternal diet enriched in olive oil. Here, we aim to evaluate targets of miR21 related to mTOR pathway regulation in the decidualized uteri of prepubertal offspring of diabetic rats fed or not with an olive oil-enriched diet.
Methods: A mild pregestational diabetic rat model was induced in F0 females by neonatal administration of streptozotocin (90 mg/kg sc). Control and diabetic females, mated with healthy males, received or not a 6% olive oil-enriched diet from day 1 of pregnancy until parturition. Female offspring (F1) were evaluated on postnatal day 30, after induction of decidualization (PMSG 50 UI- hCG 50 UI). MiR-21 targets PTEN and FOXO1, mTOR pathway negative regulators, were evaluated by RT-qPCR and mTOR pathway activity was evaluated by Western Blot.
Results: The offspring of diabetic rats showed increased PTEN and FOXO1 gene expression in the decidualized uteri (1.54 and 1.68 fold-change respectively, p&lt;0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet. They also showed altered activity of mTOR pathway: reduced phosphorylated-rpS6/total rpS6 ratio (-75%) and phosphorylated-4EBP1/total 4EBP1 ratio (-56%) (p&lt;0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet.
Conclusions: In the decidualized uteri of diabetic rat offspring, increased expression of miR21 target genes that negatively regulate mTOR activity and reduced mTOR activity suggest diabetes-induced programming of dysregulation of a signaling pathway relevant for decidualization, that can be prevented by a maternal olive oil-enriched diet.

Disclosure
C.R. Gatti: None. F.J. Schibert: None. M.L. Leonardi: None. R. Higa: None. A. Jawerbaum: None.

Funding
FONCYT (PICT 2020a -0933)
1218-P: A Critique of Defective Insulin Secretion and Insulin Sensitivity as a Precision Approach to Gestational Diabetes
Authors: JONES DANIELLE , KUSINSKI LAURA C. , MEEK CLAIRE L. 
Published: June 2024

Introduction: Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency, both) and demonstrated associations with clinical outcomes. We assessed if this approach is analytically robust, reproducible in a different population and useful diagnostically, prognostically or therapeutically in clinical practice.
Methods: 1308 pregnant women with &gt;1 risk factor having an oral glucose tolerance test were recruited. Specimens were collected for analysis of glucose (standard and enhanced procedures), HbA1c and insulin. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA-2S&lt;25th centile of normal glucose tolerance (NGT) population); insulin-insufficient GDM (HOMA-2B &lt;25th centile); both or neither. We assessed associations with pregnancy outcomes using logistic regression.
Results: Using optimal specimen handling, 1027/1308 (78.5%) women had NGT, 135/1308 (10.3%) had insulin-resistant GDM, 73/1308 (5.6%) had insulin-insufficient GDM and 2/1308 (0.2%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71/1308 (5.4%) had GDM with HOMA-2S and HOMA-2B both &gt;25th centile (GDM-neither). This novel subgroup appeared insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinemia suggesting an isolated postprandial defect in insulin sensitivity, not captured by HOMA-2B or HOMA-2S. Women within most GDM subgroups had comparable pregnancy outcomes to normoglycaemic women. Similar findings were evident using different indices and standard specimen handling techniques.
Conclusions: Precision categorisation of GDM using HOMA-2S and HOMA-2B does not provide useful diagnostic, prognostic or therapeutic information, but distinguished a novel subgroup of GDM, characterised by an isolated postprandial defect in insulin sensitivity.

Disclosure
D. Jones: None. L.C. Kusinski: None. C.L. Meek: Research Support; Dexcom, Inc.

Funding
OPHELIA study was funded by the EFSD- Sanofi innovative outcomes project (2017; OPHELIA pilot study) and the NIHR Cambridge BRC. CLM is supported by Diabetes UK through an intermediate clinical fellowship (17/0005712; ISRCTN number 90795724) and the EFSD-Novo Nordisk Foundation Future Leader’s Award (NNF19SA058974).
1226-P: Inflammation Biomarkers Do Not Mediate Improvement in Markers of Insulin Resistance Seen in Postpartum Obese and Overweight Women Who Are Breastfeeding
Authors: OLIVEIRA JULIA M. , FERRARO ALEXANDRE A. , DUALIB PATRICIA , ALMEIDA-PITITTO BIANCA 
Published: June 2024

Introduction: Studies suggest that breastfeeding (BF) decreases the risk of T2DM in Gestational Diabetes Mellitus (GDM) women. The mechanisms by which this improvement occurs are poorly understood. Our objective was to analyze the association of BF with markers of insulin resistance (MIR) and the potential mediation effect of subclinical inflammation (SI) in this association, in women with overweight/obesity and GDM.
Methods: This prospective study enrolled a convenience sample of 99 pregnant women followed from the 1st trimester up until 2-6 months postpartum. Blood was drawn at postpartum. A latent variable of SI was inferred indirectly through a mathematical model from the observable variables: adiponectin, branched chain amino acids, E-selectin, copeptin, zonulin and lipopolysaccharide (LPS). Linear regression models showed the association of BF on MIR, adjusted for covariables identified by the software Daggity. Mediation analyses were performed to determine the total, direct and the indirect effect (via SI) of BF on MIR.
Results: Women who predominantly breastfed (BF group = 44) had lower levels of triglycerides (TG), fasting glucose and insulin, TG/HDL ratio, TyG index, and HOMA-IR. LPS levels were lower in the BF group [6.8 (4.2-10.6) vs 9.2 (6.9-11.5)ng/mL, p=0.048] while other variables were similar among groups. In linear regression models an inverse association was observed between BF and fasting glucose [-6,60(-11.06 to -2.14), p=0.004), HOMA-IR [-0.26(-0.49 to -0.03), p=0.026] and TyG index [-004(-0.06 to -0.01), p=0.003] adjusted for GDM, parity, pre-gestational BMI, scholarity, weight gain during pregnancy and mode of delivery. Mediation analysis showed that SI did not mediate the results seen on the linear regression models.
Conclusion: BF is associated with an improvement in MIR in postpartum obese/overweight women, regardless of GDM. SI did not mediate the association between BF and improvement in MIR.

Disclosure
J.M. Oliveira: None. A.A. Ferraro: None. P. Dualib: None. B. Almeida-Pititto: None.
1234-P: Early Prediction of Gestational Diabetes Based on Novel Biomarkers and Risk Factors in Early and Midpregnancy—A Longitudinal Study
Authors: YANG JIAXI , SACKS DAVID B. , TSAI MICHAEL Y. , CHEN JINBO , ZHANG CUILIN 
Published: June 2024

Objectives: We aimed to improve early GDM prediction using a comprehensive biomarker panel in early and mid-pregnancy, considering clinical accessibility.
Methods: In a US study of 2802 multi-racial/ethnic pregnant individuals, we assessed 91 cardiometabolic biomarkers at gestational weeks 10-14 (random blood) and 15-26 (fasting) among 107 GDM cases and 214 controls. Biomarkers significantly associated with GDM were selected for prediction and categorized for clinical accessibility: Group I (routine clinical tests like HbA1c, hs-CRP, lipids), Group II (less routinely assessed biomarkers like IGF axis markers, adipokines), Group III (specialty lab-required targeted metabolomics like amino acids (AAs) and phospholipid fatty acids (FAs)). We developed a comprehensive full model incorporating these biomarkers alongside conventional predictors (age, BMI, plasma glucose) and alternative models based on clinical accessibility. Model performance was evaluated by AUC, proportion of cases followed (PCF, %), and proportion needed to follow (PNF, %).
Results: At 10-14 GW, the full model had the highest discriminative accuracy, AUC of 0.842. Similarly, the full model at 15-26 GW had the highest accuracy, AUC of 0.829. The addition of novel biomarkers improved clinical applications as demonstrated by PCFs and PNFs. For instance, at 10-14 GW, following women with a GDM risk above 80% as estimated by our models would identify 69.5% of GDM cases in the full model vs. 49.1% in the conventional model. To identify 90% of GDM cases, the proportion of women needed to follow based on the estimated risks would be 46.1% in the full model vs. 71.1% in the conventional model.
Conclusion: A selected panel of biomarkers using early-pregnancy random plasma samples can be as predictive as those using mid-pregnancy fasting samples. HbA1c, key IGF axis markers and adipokines, and selected phospholipid FAs and AAs effectively predict GDM risk, offering meaningful clinical utility.

Disclosure
J. Yang: None. D.B. Sacks: Other Relationship; Sebia, Trinity. M.Y. Tsai: None. J. Chen: None. C. Zhang: None.

Funding
Dean's Office, Yong Loo Lin School of Medicine, National University of Singapore; The Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and American Recovery and Reinvestment Act funding: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z