bluuebunny/crossref_metadata_2025_split huggingface dataset:
1097-P: Association between Adipokines and Glycemia in Children under Age 8—The PROGRESS Cohort of Mexico
Authors: BEYH YARA S. , WU HAOTIAN , VENKAT NARAYAN K.M. , STAIMEZ LISA R. , RAMAKRISHNAN USHA , BHASIN MANOJ K. , CRUZ TOLENTINO DOLORES MARI , ESTRADA-GUTIERREZ GUADALUPE , YITSHAK SADE MAAYAN , WRIGHT ROBERT O. , TELLEZ-ROJO MARTHA M. , BACCARELLI ANDREA 
Published: June 2023

Background: The increased incidence of type 2 diabetes is closely linked to obesity, in which an accumulation of adipocytes leads to the dysregulated production of adipokines. In adults, several adipokines contribute to the development of glycemic dysregulation, however, the role of adipokines on childhood glycemia is poorly understood. We examine the longitudinal association between adipokines and glycemia using multiple timepoint data from children in Mexico City.
Methods: Children from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort (948 children, 52% male) were followed longitudinally after birth. Leptin, adiponectin, glucose, and HbA1c were measured at 4, 6, and 8 years, and fasting insulin at 8 years. Adiponectin to leptin ratio (ALR) and HOMA2 (B/IR/S) indices were computed. Longitudinal association between adipokines and each of glucose and HbA1c was examined by linear mixed models. Association between adipokines and insulin and the HOMAs at age 8 was examined by multivariable linear regression. All models were adjusted for maternal and child covariates.
Results: Between ages 4 and 8 years, average levels of leptin dropped from 15.7 to 13.7 ug/mL; adiponectin increased from 3.1 to 10.8 ng/mL; and ALR dropped from 9.1 to 3.1 ug/ng. Longitudinally, across timepoints 4, 6, and 8 years after birth, there was no association between adipokines and glycemia. However, the cross-sectional analysis at age 8 years found an association between leptin and insulin (1.03, 95% CI: 1.00, 1.07), HOMA2-B (1.02, 95% CI: 1.00, 1.04), HOMA2-IR (1.03, 95% CI: 1.00, 1.07), and HOMA2-S (0.97, 95% CI: 0.94, 0.99). Similar associations were observed in males and females.
Conclusion: In this prepubertal cohort, leptin was associated with insulin and with HOMA indices at age 8. Further investigation is needed to understand the role of adipokines in the development of T2DM in children and the risk factors that may alter adipokine metabolism.

Disclosure
Y.S.Beyh: None. R.O.Wright: None. M.M.Tellez-rojo: None. A.Baccarelli: None. H.Wu: None. K.Narayan: None. L.R.Staimez: None. U.Ramakrishnan: None. M.K.Bhasin: None. M.Tolentino dolores: None. G.Estrada-gutierrez: None. M.Yitshak sade: None.

Funding
National Institute of Environmental Health Sciences (R01ES032242, R01ES021357, R01ES013744, P30ES009089)
1099-P: Plasma Amino Acid Profiles in Childhood Predict 10-Year Risk of Insulin Resistance in Adulthood—The BCAMS Study
Authors: GAO SHAN , LI MING , GROUP BCAMS 
Published: June 2023

Objective Insulin resistance (IR) is the critical step in the development of type 2 diabetes. Recent cross-sectional studies in children demonstrate plasma amino acids such as branched-chain and aromatic amino acids are associated with IR, however, information is scant regarding whether these associations in childhood persist over time and predict diabetes risk in young adults. We aimed to examine whether circulating amino acids in childhood predict 10-year risk of IR in early adulthood.
Research design and Methods: This was a 10-year longitudinal study from childhood to early adulthood. A total of 961 subjects aged 6-18 years at baseline participated in the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS). Serum insulin was determined by in-house ELISA with no cross-reaction with proinsulin, and plasma amino acids were profiled using targeted LC-MS/MS. IR was determined by the homeostatic model assessment of insulin resistance (HOMA-IR).
Results: At baseline, after adjusting for age, gender, tanner stage, diet score, exercise, residence and BMI, 17 amino acids were closely correlated with HOMA-IR and nine with impaired fasting glucose (IFG) in childhood (p &lt; 0.05 for all). Among them, Isoleucine showed the strongest association with IR (OR=2.04, 95% CI 1.65-2.54, P&lt;0.001), and alanine was the strongest predictor of IFG (OR =1.52, 95%CI 1.22-1.91, P&lt;0.001). Prospectively, after adjusting for the covariates at baseline, four amino acids have a significant predictive effect on the risk of IR at 10-years follow-up, of which alanine was the strongest predictor [OR=1.38, 95% CI (1.02, 1.85), P=0.035].
Conclusion: Our findings suggest the changes in amino acid metabolism not only link IR in childhood, but also persist into adulthood and may heighten type 2 diabetes risk later in life.

Disclosure
S.Gao: None. M.Li: None. Bcams group: n/a.

Funding
National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-016); Capital's Funds for Health Improvement and Research (2020-2Z-40117); Key Program of Beijing Municipal Science &Technology Commission (D111100000611001, D111100000611002)
1102-P: Joint Effect of GLP-1R and Exposure to Gestational Diabetes on Glucose Regulation in Adolescents—The EPOCH Study
Authors: HARRALL KYLIE K. , GLUECK DEBORAH H. , SAUDER KATHERINE A. , CREE-GREEN MELANIE , DABELEA DANA 
Published: June 2023

Exposure to gestational diabetes (GDM) and polymorphisms of the glucagon-like-peptide-1 receptor gene (GLP-1R) are both associated with type 2 diabetes risk. In adults, GLP-1R mutations were associated with altered first phase insulin secretion and glucose levels during an oral glucose tolerance test (OGTT). We explored a potential joint association between GLP-1R and GDM exposure on glucose regulation in youth. Exploring Perinatal Outcomes among Children (EPOCH) participants with (N = 86) and without (N = 189) GDM exposure had 2-hour 75g OGTT at ~17 years. DNA was genotyped by microarray. Plink 2.0 was used to extract genotyped and imputed GLP-1R polymorphisms. Glucose and insulin measured at 0, 30 and 120 minutes were used to calculate areas under the curve (AUC), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulinogenic index (IGI), and disposition index (DI). Linear models tested the interaction of GLP-1R rs1042044 homozygosity of the minor allele and GDM on each outcome. Homozygotes exposed to GDM had higher baseline, 30, 120 minute and AUC for glucose (p &lt; 0.0001), and lower insulin AUC (p = 0.046) than others (Figure 1), but not significantly different HOMA-IR, IGI and DI. Our data indicates a joint effect of GDM exposure and GLP-1R on glucose levels in youth, potentially due to reduced first phase insulin secretion. Further studies are needed to replicate this finding.

Disclosure
K.K.Harrall: None. D.H.Glueck: None. K.A.Sauder: None. M.Cree-green: Consultant; Pollie Inc, Research Support; Amino Corp LLC. D.Dabelea: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068001)
1103-P: Prediabetes and Associated Characteristics among Asian/Pacific Islander Adolescents with Obesity
Authors: CHU CLARENCE , RODRIGUEZ LUIS A. , CHANDRA MALINI , GREENSPAN LOUISE , BACONG ADRIAN M. , LO JOAN C. 
Published: June 2023

Background: There are limited data regarding modifiable lifestyle behaviors and prediabetes among US Asian/Pacific Islander (API) children. This study characterizes the association of obesogenic behaviors and weight with prediabetes among API adolescents with obesity receiving pediatric care.
Methods: We used retrospective data from 3,233 API adolescents aged 13-17 years in a US healthcare system who had well child visits in 2016-2019, provided well-check information on health behaviors, had BMI ≥95th percentile, and HbA1c level (within 1 year). Age, sex, self-reported daily obesogenic behaviors (eating &lt;5 servings of fruits/vegetables, drinking ≥12 oz juice/soda, exercising for &lt;60 minutes, &gt;2 hours screen time), obesity level (Class I,2,3) and neighborhood deprivation index (NDI) were examined. Prediabetes was defined as HbA1c 5.7-6.4%; those with HbA1c ≥6.5% or diabetes diagnosis were excluded. Multivariable logistic regression was used to examine the association of these factors and prediabetes.
Results: Among 3,233 API adolescents (mean age 14.6 ± 1.4 y; 63.8% male) with obesity, 22.4% had prediabetes (84.4% had HbA1c 5.7-5.9%). Prediabetes did not differ by age or sex but increased with obesity level (20.1%, 25.2%, 33.2% for Class 1, 2, 3 obesity, respectively). In unadjusted analyses, low exercise was marginally associated with prediabetes (p=0.07) but not diet or screen time. In fully adjusted multivariable analyses, obesity severity (OR 1.98 [95% CI 1.47-2.64] for class 3, OR 1.34 [1.10-1.63] for class 2 vs 1), and low exercise (OR 1.20 [1.01-1.44]) were associated with increased odds of prediabetes, whereas other modifiable behaviors were not.
Conclusion: About 1 in 5 API adolescents with obesity had prediabetes, associated with obesity severity and low exercise. These findings support efforts that address obesity and promote physical activity in API children to reduce the risk of diabetes. Further studies should examine potential differences by ethnic group.

Disclosure
C.Chu: None. L.A.Rodriguez: None. M.Chandra: None. L.Greenspan: None. A.M.Bacong: None. J.C.Lo: None.

Funding
Kaiser Permanente Northern California
1104-P: South Asian vs. White Adolescents Have Lower Insulin Sensitivity and Higher Insulin AUC
Authors: HITT TALIA A. , STEFANOVSKI DARKO , MALINA SARA , WANG CYNTHIA X.D. , ZEMEL BABETTE S. , KELLY ANDREA , MAGGE SHEELA N. 
Published: June 2023

Background: T2D occurs at higher rates in South Asian (SA) adults, even at non-overweight/obese BMI. OGTT metrics were compared in SA vs White (W) adolescents to identify early contributors to increased T2D risk.
Methods: Healthy SA and W adolescents, ages 12-21y, with BMI ≥80%ile (or ≥23kg/m2 if ≥18y) underwent 10-sample 180-min OGTT to determine incremental insulin AUC (iAUC), Oral Minimal Model insulin sensitivity (Si), and disposition index (DI: Si x insulin iAUC at 180min). Ancestry differences in OGTT outcomes were compared using linear regression adjusted for age, sex, and BMI.
Results: For n=21, age [median (IQR) W: 20.1y (16.1, 21.3), SA: 21.0 (20.3, 21.6)], sex [W: 6F, SA: 4F], and BMI [W: 25.2kg/m2 (24.7, 31.4), SA: 24.6 (24.1, 27.9)] were not different for SA vs W. Fasting glucose [β=7.1, p=0.01; SA: 98.0mg/dL (92.0, 102.5), W: 89.0mg/dL (87.0, 93.5)], fasting insulin [β=7.0, p=0.005], insulin iAUC at 30min [β=1192, p=0.02], and log-transformed insulin iAUC at 180min [β=0.98, p=0.002] were higher, and log-transformed Si [β=-1.07, p=0.008] lower in SA than W. HbA1c, OGTT 1h and 2h glucose, and DI did not differ.
Conclusions: Higher OGTT insulin in overweight SA adolescents contrast with reduced insulin found in SA adults and suggests reduced Si and insulin hyper-secretion are precursors to β-cell failure and T2D in SA adults. Understanding T2D mechanistic differences by ancestry may lead to improved T2D treatments.

Disclosure
T.A.Hitt: None. D.Stefanovski: None. S.Malina: None. C.X.D.Wang: None. B.S.Zemel: None. A.Kelly: None. S.N.Magge: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK115648); National Institutes of Health (UL1TR001878, UL1TR001079)
1105-P: Development and Implementation of a Multidisciplinary Clinic Focused on Youth-Onset Type 2 Diabetes
Authors: SCHAAF LISA R. , CRAIL JENNIFER , XANTHAKOS STAVRA , SIZEMORE JENNIFER , CRIMMINS NANCY A. , HELMRATH MICHAEL , LEY SANITA , MORWESSEL NANCY , RIEGLER ALLEN , TARIQ FATIMA , SHAH AMY S. 
Published: June 2023

Diabetes self-management education and lifestyle interventions are the cornerstone of type 2 diabetes (T2D) care; however, the higher risk of comorbidities, including depression, among youth with T2D requires a comprehensive care model. Traditionally sub-specialty care relies on a referral model placing the burden on the patient. In response, we developed a pediatric T2D multidisciplinary clinic (MDC) - a single physical location where patients have access to various sub-specialists. The goals of the MDC are to provide access to lifestyle modifications, identify patients who need access to sub-specialty care through screening labs, and improve health care access.
We conducted a retrospective chart review of youth seen in the T2D MDC clinic at Cincinnati Children's Hospital from 1/2020 - 12/2021. We evaluated the frequency that youth met with each specialist and completion rates of annual screening labs.
The cohort consisted of 227 youth with T2D (mean age 17.6 years, mean BMI 40.9%, 64% female, 50% Black or African American, 65% public insurance). All patients met with a diabetes provider and 81.2% met with a registered dietitian/certified diabetes education specialist. Gastroenterology met with 55.8% of the patients who had elevated liver enzymes, exercise physiology met with 51.6% of patients, social work met with 44.1% of patients, clinical psychology met with 27.3% of patients, and bariatric surgery met with 9.7% of patients. Percent completion of annual labs were: 98.2% for HbA1c, 84.6% for urine microalbumin, 83.7% for lipids, 89.9% for liver function, and 59.5% for retinopathy.
The majority of patients received diabetes and nutrition education and annual screening labs. Exercise counseling and sub-specialty care remain below 60% in part because these services are not available at every MDC clinic. Our goals are to increase access to subspecialty care within the MDC's and consider additional care delivery methods to provide comprehensive care to youth with T2D.

Disclosure
L.R.Schaaf: None. F.Tariq: None. A.S.Shah: None. J.Crail: None. S.Xanthakos: None. J.Sizemore: None. N.A.Crimmins: None. M.Helmrath: None. S.Ley: None. N.Morwessel: None. A.Riegler: None.
1107-P: Insulin Sensitivity Changes from Adolescence to Young Adulthood
Authors: BRAXTON MORGAN , JAGER JUSTIN , AYERS STEPHANIE , OLSON MICAH , SHAIBI GABRIEL Q. 
Published: June 2023

Background: Latino youth are disproportionately impacted by type 2 diabetes (T2D) and youth onset T2D is more aggressive and resistant to conventional treatment. Early prevention efforts are warranted for high-risk pediatric populations, but little is known about the long-term effects of such interventions. The purpose of this study was to examine health trajectories following a diabetes prevention program for Latino adolescents with obesity who are now young adults.
Methods: Participants (N=61) completed a 3-month lifestyle intervention as adolescents (Mage = 15.4) and were re-contacted ~5 years post-intervention (Mage = 20.7 years). Measures included BMI and the Matsuda Index to estimate insulin sensitivity. Latent profile analysis was used to examine heterogeneity in changes in insulin sensitivity over time.
Results: Participants exhibited significant reductions in BMI post-intervention (from 34.8±4.7 to 34.1±4.7, p &lt;.001); however, BMI increased at 5-year follow up (40.5±8.4, p &lt;.001). Similarly, insulin sensitivity increased by 23.5% post-intervention (from 1.7±1.0 to 2.1±1.0, p &lt;.001) but returned to baseline levels at 5-years (1.8±1.4). Latent profile analysis identified two distinct trajectories in insulin sensitivity. Profile 1 was characterized by lower baseline insulin sensitivity (1.4 [1.2, 1.7]) followed by a 36% increase post-intervention (1.9 [1.6, 2.2]) that remained above baseline at 5 years (1.7 [1.3, 2.1]). Profile 2 exhibited a 31% increase from baseline insulin sensitivity (2.9 [1.6, 4.2]) after the intervention (3.8 [2.8, 4.8]) that fell below baseline at 5 years (2.7 [0.6-4.8]) Female sex significantly differentiated the trajectories and was associated with profile 1.
Discussion: Despite improvements in diabetes-related health immediately following the intervention, weight gain and decreased insulin sensitivity persisted into young adulthood. The unique profiles suggest that there may be specific factors such as sex that can differentiate health trajectories over time.

Disclosure
M.Braxton: None. J.Jager: None. S.Ayers: None. M.Olson: Advisory Panel; Rhythm Pharmaceuticals, Inc. G.Q.Shaibi: None.

Funding
National Institute on Minority Health and Health Disparities (U54MD002316)
1119-P: Improved Glycemic Control with Less Effort during Real-World MiniMed 780G Advanced Hybrid Closed-Loop (AHCL) System Use by Children with T1D
Authors: MCVEAN JENNIFER , ARRIETA ARCELIA , CORDERO TONI L. , CASTAÑEDA JAVIER , COHEN OHAD 
Published: June 2023

Objective: To evaluate real-world glycemic outcomes and insulin delivery based on TIR (70-180mg/dL) before and after MiniMed™ 780G system use by children with T1D.
Methods: MiniMed™ 780G system data from 2,516 users aged ≤15 years (from Europe, the Middle East and Africa) who provided assent, were uploaded between Aug 2020 and Jun 2022. For users with ≥10 days of sensor glucose (SG) data, glycemic outcomes (e.g., SG, time in SG ranges and glucose management indicator [GMI]), insulin delivered, and use of the 100mg/dL* glucose target and 2hrs active insulin time (recommended settings) were summarized and stratified by baseline TIR quartiles. Results: After AHCL initiation, overall glycemic control (GMI) improved and TIR increased in all TIR quartiles, with increased system-initiated insulin (auto basal and auto correction) delivery and fewer user-initiated boluses (Figure). Greater recommended settings use was associated with a higher TIR (4th quartile) and less recommended settings use was associated with a lower TIR (1st quartile).
Conclusion: Children with T1D using the MiniMed™ 780G system had improved glycemic control evidenced by increased TIR with less effort (i.e., fewer user-initiated boluses). Glycemic control was improved across the spectrum of users and use of recommended settings enhanced outcomes.

Disclosure
J.Mcvean: Employee; Medtronic. A.Arrieta: Employee; Medtronic. T.L.Cordero: Employee; Medtronic. J.Castañeda: Employee; Medtronic. O.Cohen: Employee; Medtronic.
1120-P: Higher Real-World Time in Range Demonstrated in Children Using Recommended MiniMed 780G (AHCL) Settings
Authors: MCVEAN JENNIFER , ARRIETA ARCELIA , CORDERO TONI L. , CASTRO MATIAS , CASTAÑEDA JAVIER , COHEN OHAD 
Published: June 2023

Objective: The present study evaluated real-world pediatric glycemia during use of MiniMed™ 780G recommended settings (100 mg/dL* glucose target [GT] and 2hrs active insulin time [AIT]).
Methods: Overall mean TIR, after AHCL initiation, in the pediatric pivotal trial (ages 7-17 years) was 70.3% (N=160).1 For participants using recommended settings &gt;95% of the time, mean TIR was 73.4% (N=19). In this abstract, we present real-world glycemic outcomes in children (≤15 years) from multiple continents using a range of GT and AIT settings, versus the recommended GT and AIT settings. Assented real-world users with ≥10 days of sensor glucose (SG) data from EMEA (N=3,211 in Europe, the Middle East, and Africa) and Latin America (N=332) uploaded system data between Aug 2020-Sep 2022. Outcomes included the mean of SG, glucose management indicator and percentage of time spent below, within and above target (70-180 mg/dL) range.
Results: Real-world outcomes from children in EMEA and Latin America using overall AHCL settings met consensus goals (Figure)2 and TIR increased further when recommended settings were used.
Conclusion: Findings in a population of children from around the world with T1D who used MiniMed™ 780G AHCL at recommended settings (versus a range of settings) had the highest time in range, without compromising time below range.

Disclosure
J.Mcvean: Employee; Medtronic. A.Arrieta: Employee; Medtronic. T.L.Cordero: Employee; Medtronic. M.Castro: Employee; Medtronic. J.Castañeda: Employee; Medtronic. O.Cohen: Employee; Medtronic.
1128-P: Changes in Gut Bacteriome Composition on Low-Carbohydrate Diet in Children with Type 1 Diabetes
Authors: NEUMAN VIT , HLINÁKOVÁ LUCIE , PLACHY LUKAS , PETRUZELKOVA LENKA , OBERMANNOVA BARBORA , PRUHOVA STEPANKA , KOLOUSKOVA STANISLAVA , HAVLIK JAROSLAV , SUMNIK ZDENEK , CINEK ONDREJ 
Published: June 2023

Objectives: Low-carbohydrate diet (LCD) is a controversial but popular dietary choice for many children and adolescents with type 1 diabetes (CwD). In a cross-over trial with LCD (clinicaltrials.gov NCT05078658), we assessed whether even a short period of tightly controlled LCD is able to change the gut bacteriome in CwD.
Methods: Twenty CwD (aged 15.1±3.0 years) were recruited into an intervention trial with a 5-week period of LCD (95±3 g carbs daily) followed by 5 weeks of regular carbohydrate diet (RCD) (193±18 g carbs daily) with the order randomized. The diets did not differ in energy intake (8360 vs. 8392 kJ, P=0.08). The fecal samples were collected regularly before, after and throughout the interventions (median number of samples collected per subject was 12, IQR 10-15). The fecal bacteriome was assessed using massively parallel sequencing of the variable regions V3-V4 of 16S rDNA. Mixed effects regression models were built where responses were principal components of the bacteriome community, alpha diversity indices and individual taxa. The predictors were the type of the diet, time since start of the diet and randomized order of the diets.
Results: We observed shifts in the bacteriome community composition on the LCD which were apparent at all taxonomic levels (P for various principal components ranging from 5×10-4 to 0.015); their magnitude was however moderate. Of individual taxa, Bifidobacterium sp. and its higher taxonomic categories were negatively associated with LCD; the overall effects observed on the community composition were however broader than could be explained by changes in this single taxon. The alpha diversity decreased with time regardless of the intervention sequence, but did not associate with LCD.
Conclusions: Even a short period of LCD is associated with subtle yet significant changes in the stool bacteriome community composition mainly in the Bifidobacterium sp. The observed changes may help us understand the possible effects of LCD on T1D.

Disclosure
V.Neuman: None. O.Cinek: None. L.Hlináková: None. L.Plachy: None. L.Petruzelkova: None. B.Obermannova: None. S.Pruhova: None. S.Kolouskova: None. J.Havlik: None. Z.Sumnik: None.

Funding
Czech Ministry of Health (AZVNU21-01-00085)