bluuebunny/crossref_metadata_2025 huggingface dataset:
1280-P: Improving Type 1 Diabetes (T1D) Prediction by Incorporating Growth Features into Landmark Models
Authors: LI ZHIGUO , ANAND VIBHA , DUNNE JESSICA L. , FROHNERT BRIGITTE I. , HAGOPIAN WILLIAM , HYOTY HEIKKI , MAZIARZ MARLENA , ZIEGLER ANETTE-GABRIELE , TOPPARI JORMA ,   T1DI STUDY
Published: June 2020

We explored the association between growth features and T1D development using landmark analysis at different ages. Analysis included individuals from 2 birth cohort studies: DAISY and BABYDIAB (n=2,664; 129 progressed to T1D). Using height and weight measured over time, percentiles for age were calculated. Missing values were imputed using LMS parameters of CDC growth charts. Rates of change of percentiles were computed over the prior year. Twelve ages (1-12 years) were used for landmark analysis with Random Survival Forest to predict probability of T1D onset in the 1- to 19-year follow up windows. The baseline model used HLA risk group, sex, T1D family history and breastfeeding history. The full model added growth features: height and weight percentiles at age and change in percentiles. Performance was measured using C-index and feature importance was ranked. Incorporating growth features significantly improved prediction accuracy of T1D onset for 95% of combinations of landmark ages and prediction window sizes (Table 1, not all ages and windows shown). The order of features from most to least predictive is: HLA group, rates of height and weight changes, height and weight percentiles, family history, breastfeeding and sex. This analysis demonstrates that using growth features can significantly improve prediction of T1D.

Table 1: C-Index with and without inclusion of growth features for landmark age of 3 years.

Disclosure

Z. Li: None. V. Anand: None. J.L. Dunne: None. B.I. Frohnert: None. W. Hagopian: Consultant; Self; Novo Nordisk Inc. H. Hyoty: None. M. Maziarz: None. A. Ziegler: None. J. Toppari: None.

Funding

JDRF (1-IND-2019-717-I-X, 1-SRA-2019-722-I-X, 1-SRA-2019-720-I-X, 1-SRA-2019-721-I-X, 1-SRA-2019-719-I-X, 1-SRA-2019-723-I-X)
1283-P: Multicenter Assessment of the Pancreas in Type 1 Diabetes (MAP-T1D)
Authors: VIROSTKO JOHN , WILLIAMS JONATHAN M. , HILMES MELISSA A. , DU LIPING , KANG HAKMOOK , RUSSELL WILLIAM E. , TRIOLO TAYLOR M. , PHILIPSON LOUIS H. , SIMS EMILY K. , EVANS-MOLINA CARMELLA , THOMAS HELEN E. , KAY THOMAS , GREELEY SIRI ATMA W. , STECK ANDREA , POWERS ALVIN C. , MOORE DANIEL J.
Published: June 2020

Individuals both at risk for and newly diagnosed with type 1 diabetes (T1D) have a reduced pancreas volume as assessed by MRI. Furthermore, multiparametric quantitative MRI techniques have detected focal alterations in the T1D pancreas. However, performing quantitative MRI techniques in multi-site trials is challenging due to differences in MRI hardware and software. To determine if quantitative MRI measurements in T1D can be performed at different institutions, 5 academic centers (see author affiliation) have established the Multicenter Assessment of the Pancreas in T1D (MAP-T1D) group to develop harmonized MRI acquisition and image processing protocols. We established and implemented an MRI protocol for pancreas imaging on both Siemens and Philips MRI platforms at 5 imaging centers, consisting of T1- and T2-weighted anatomical images, diffusion-weighted MRI, magnetization transfer MRI, and longitudinal relaxation (T1) mapping. Imaging phantoms assessing volume, diffusion, magnetization transfer ratio, and T1 were created and imaged at each institution to test the reproducibility of multiparametric MRI. Measurement of phantom volume yielded an average error of 1.5% from the true volume. The apparent diffusion coefficient, magnetization transfer ratio, and T1 phantoms had coefficients of variation of 6.0%, 10.0%, and 9.5%, respectively, between sites. To assess the reproducibility of human MRI scanning, we recruited 5 healthy subjects to travel to 4 sites for imaging using the standardized MRI protocol. Pancreas volume measured at multiple sites had an average coefficient of variation between scans of 8.3% with a maximum difference of 17% (n = 9 MRIs). This study demonstrates the feasibility of quantitative pancreas MRI across multiple sites. Standardization of pancreas MRI acquisition and processing will accelerate integration of pancreas volume and other quantitative MRI measurements in future multi-center clinical trials of T1D.

Disclosure

J. Virostko: None. J.M. Williams: None. M.A. Hilmes: None. L. Du: None. H. Kang: None. W.E. Russell: None. T.M. Triolo: None. L.H. Philipson: None. E.K. Sims: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb. H.E. Thomas: None. T. Kay: None. S.W. Greeley: None. A. Steck: None. A.C. Powers: None. D.J. Moore: None.

Funding

JDRF (3-SRA-2019-759-M-B, 3-SRA-2015-102-M-B)
1286-P: Identification of Atypical Pediatric Diabetes Using Electronic Medical Records (EMR)
Authors: ASTUDILLO MARCELA , TOSUR MUSTAFA , SILLER ALEJANDRO F. , BALASUBRAMANYAM ASHOK , REDONDO MARIA J.
Published: June 2020

We aimed to identify cases of rare or atypical pediatric diabetes who may be candidates for studies to understand their etiology and pathogenesis. We tested two strategies in a large pediatric hospital in Southwestern USA. STRATEGY 1: We designed a questionnaire that would allow a health-care provider to rule out typical diabetes types by manual EMR review. This questionnaire was first applied to the EMR of 50 youth (0-21 years old [y/o]) consecutively seen in the diabetes outpatient clinic, then modified to address problems identified, and tested in a second iteration, and on 50 additional cases (n=100). STRATEGY 2: In collaboration with local EMR analysts, we built three queries to generate periodic, automated reports of possible pediatric atypical diabetes cases: unknown type, type 2 diabetes (T2D) diagnosed <10 y/o, and autoantibody-negative type 1 diabetes (T1D). Diabetes type (i.e., unknown, T1D or T2D) was determined by the treating pediatric endocrinologist, through a customized flowchart embedded in the EMR. STRATEGY 1: We found 6 cases (6%) of atypical diabetes (mean age at diagnosis 11 y/o [SD 2.64], 16.6% male, 33% non-Hispanic White [NHW] and 66.6% Hispanic [Hisp]). STRATEGY 2: Unknown diabetes type: 67 cases (15, out of 6676 total diabetes cases), with mean age at diagnosis 12.6 y/o (SD 3.3), 32.8% male, 23.8% NHW, 47.6% Hisp, 25.4% African-American (AA), 3.2% other. Out of 1142 children with T2D, 64 (6.6%) cases were diagnosed <10 y/o, with mean age at diagnosis 8.6 y/o (SD 1.6), 20.3% male, 4.7% NHW, 65.6% Hisp, 28.1% AA, 1.6% other. Out of 680 cases of new onset T1D, 38 (5.6%) were negative for islet autoantibodies (IAA, GAD, IA-2), with mean age at diagnosis 11.3 y/o (SD3.8); 57.9% male, 50% NHW, 19.4% Hisp, 22.3% AA, 8.3% other. In sum, we designed and tested two strategies that use EMR to identify possible atypical pediatric diabetes cases for further studies that may shed light on the heterogeneity of pediatric diabetes, possibly opening new opportunities for diagnosis, treatment and prevention.

Disclosure

M. Astudillo: None. M. Tosur: None. A.F. Siller: None. A. Balasubramanyam: None. M.J. Redondo: None.
1294-P: Clinically Significant Hypoglycemia Is Rare in Youth with T1D during Partial Clinical Remission
Authors: ADDALA ANANTA , GU ANGELA , ZAHARIEVA DESSI , PRAHALAD PRIYA , BUCKINGHAM BRUCE A. , SCHEINKER DAVID , MAAHS DAVID M.
Published: June 2020

Lower CGM glucose is typical after the diagnosis of T1D and the initiation of insulin treatment. Although ADA guidelines now state that glycemic targets can be lower during partial clinical remission (PCR), little guidance is offered on the optimal targets. We describe CGM glucose <70 mg/dL for youth wearing CGM by PCR status. We reviewed 201 visits from 67 records; 55 visits in PCR as defined by insulin dose adjusted A1C value <9 [(HbA1c at visit)*(4*units/kg/day)]. CGM data were collected 7 days before and after each visit. In multivariate regression, controlling for age, sex, and T1D duration, proportion of time spent <70 mg/dL was calculated in a 24-hour period and at nighttime (midnight to 6am). Our cohort is 40% female, aged 9.4±4.7 years, with 92±11% wear time, and T1D duration of 126±105 days. Time spent between 54-70 mg/dL was statistically higher at nighttime for those in PCR and the time spent <54 mg/dL was minimal for both (3.4±9.3 mins/24h, Table). There were no episodes of severe hypoglycemia. Clinically significant hypoglycemia (<54 mg/dl) is rare. Furthermore, youth in PCR have time <70 mg/dL similar to youth without T1D. A threshold alarm of 65 mg/dl may reduce hypoglycemia related alarms by 50% without increasing risk of severe hypoglycemia and warrants further study. These data support a trial of lower alarm thresholds for youth in PCR who wear CGM to avoid overtreatment of clinically insignificant lows.

Disclosure

A. Addala: None. A. Gu: None. D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. P. Prahalad: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. D. Scheinker: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.
1300-P: Empowering Youth with Diabetes (DM): Characteristics and Initial Outcomes of a Novel Diabetes Transition Program (DTP)
Authors: LIBMAN INGRID , KRALL JODI T. , FISCHL ANDREA F. , FINNEY JESSICA , DIAZ ANA M. , SIMINERIO LINDA M. , CHARRON-PROCHOWNIK DENISE , BECKER DOROTHY J.
Published: June 2020

Adolescents and young adults (AYA) with DM have increased risk of poor outcomes. The DTP was created to equip AYA with knowledge, support, and skills to foster successful lifelong DM self-management. This 1-year (4 visits) program pairs clinical care with peer-group discussions led by a multidisciplinary team focused on informed decision making of issues relevant to AYA with DM. The purpose of this study was to characterize the population referred to DTP and evaluate concerns, program adherence and outcomes. Medical records were reviewed and surveys administered. To date 153 AYA were referred (51% females, 99% T1DM, age at 1st visit 18.8±1.4 yrs, age at onset 9.7±4.7 yrs, HbA1c 9±2%). In ranking concerns of 5 complications (retinopathy, neuropathy, reproductive health complications, nephropathy and hypertension) at the 1st DTP visit, 60% of males and 57% of females who completed the survey rated retinopathy as their number 1 or 2 concern. Reproductive health and hypertension were listed as their least concern by 43% of males and 42% of females respectively. In terms of program adherence, the majority (60%, n=92) completed DTP on schedule (1 year). Of these, 42% transferred to adult care, 52% continued care at the institution and 6% were lost to follow up. Of those who did not complete DTP over 1 year (40%), 25% transferred to adult care before DTP completion, 60% are completing DTP in more than 1 year, and 15% were lost to follow up. Those who transferred to adult care (irrespective of program completion time), versus those who did not, had lower HbA1c at all DTP visits (e.g., 1st visit: 8.1 ± 1.4% vs. 9.4 ± 1.7%, p=0.01). In terms of outcomes for those that completed the program, no differences were found in HbA1c from the 1st to 4th visit.

In conclusion, AYA referred to DTP appear to be a high-risk population based on their HbA1c and suboptimal program adherence. This highlights the need for methods (e.g., telehealth) to continue to engage this population and ongoing self-management support.

Disclosure

I. Libman: Consultant; Self; Novo Nordisk A/S. J.T. Krall: Research Support; Self; Becton, Dickinson and Company. A.F. Fischl: None. J. Finney: None. A.M. Diaz: None. L.M. Siminerio: Research Support; Self; Becton, Dickinson and Company. D. Charron-Prochownik: None. D.J. Becker: None.

Funding

David Paul Diabetes Transition Care Research Initiative Fund
1301-P: Factors Predicting Diabetes Distress over 18 Months in Teens with Type 1 Diabetes (T1D)
Authors: MCGILL DAYNA E. , VOLKENING LISA K. , COMMISSARIAT PERSIS V. , WASSERMAN RACHEL M. , ANDERSON BARBARA , LAFFEL LORI M.
Published: June 2020

Background: Teens with T1D are burdened by physical, social, and emotional challenges that can lead to diabetes distress, impacting self-care and health outcomes. We assessed diabetes distress and associated factors in teens with T1D over 18 months.

Methods: At baseline, 6, 12, and 18 months, teens (N=301), ages 13-17 years, completed the Problem Areas in Diabetes Survey - Pediatric version (PAID-Peds), a validated 20-item survey measuring diabetes distress over the past month. Higher scores (range 0-100) indicate more distress; ≥41 = high distress. Mixed linear models assessed factors associated with changing diabetes distress over time.

Results: At baseline, teens (49% male, 78% white) were 15.0±1.3 (M±SD) years old with T1D duration 6.5±3.7 years; 84% were from 2-parent families. Youth checked BG 4.5±1.9 x/day; 59% were pump-treated; A1c was 8.5±1.1%. At baseline, 45% of teens endorsed high diabetes distress and females were disproportionately affected (54% vs. 36% of males, p<.01). In follow-up, 75% of teens with high baseline distress and 24% of teens with low baseline distress endorsed high distress at ≥50% of follow-up time points. High baseline distress strongly predicted subsequent distress (OR 9.6 [95% CI: 5.6, 16.5], p<.0001). Female sex and increasing A1c predicted increasing distress. In teens with high baseline distress, decreasing BG monitoring predicted increasing distress. In those without high baseline distress, only increasing A1c predicted increasing distress. Factors such as zBMI, race, family structure, household income, parental education, pump use, or use of continuous glucose monitors did not predict distress over time.

Discussion: A substantial proportion of teens with T1D experience high diabetes distress. Rising A1c is a major factor associated with worsening diabetes distress over time. Interventions targeting teens with diabetes distress and/or increasing A1c may positively impact self-care and simultaneously help to manage distress and improve A1c.

Disclosure

D.E. McGill: None. L.K. Volkening: None. P.V. Commissariat: None. R.M. Wasserman: None. B. Anderson: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding

National Institutes of Health (R01DK095273, K12DK094721, P30DK036836), JDRF (2-SRA-2014-253-M-B)
1302-P: Shared Decision Making in Type 1 Diabetes (T1D) Care: Insights from the CoYoT1 to California (CTC) Study
Authors: FLORES GARCIA JAQUELIN J. , PYATAK ELIZABETH , REID MARK W. , FOGEL JENNIFER L. , DIAZ JESUS , RAYMOND JENNIFER
Published: June 2020

Introduction: CTC is a 15-month intervention study evaluating a patient-centered, home telehealth care model for young adults (YA) ages 16-25 with T1D. The patient-centered CoYoT1 Care arm includes a shared decision-making tool completed by providers (n=3) and patients (n=47) prior to each visit. The present analysis examines how patients and providers collaborated to shape initial visit agendas. Methods: Six potential topics were each rated on a 1-5 scale, where higher values indicate greater importance. Patient and provider ratings within each topic were compared using paired t-tests. Next, ratings were compared between visits where a topic was discussed or not discussed using independent t-tests; patient and provider data were evaluated separately.

Results: Blood sugar ranges and supply/medication issues were discussed most frequently. Providers assigned higher overall importance to emotional well-being than their patients (p=0.005), but this topic was only discussed when patients assigned higher importance (p=0.001). Also, despite higher provider ratings, blood sugar ranges were only discussed when patients assigned higher importance (p=0.003). Discussion: Consistent with the CoYoT1 Care model, patients and providers collaborated to shape visit agendas, slightly favoring the patient perspective. Topics discussed were those assigned higher importance by patients and providers.

Disclosure

J.J. Flores Garcia: None. E. Pyatak: None. M.W. Reid: None. J.L. Fogel: None. J. Diaz: None. J. Raymond: None.
1304-P: Glycemic Trends in a Hockey Camp for Youth with Type 1 Diabetes (T1D)
Authors: RIDDELL MICHAEL , LI ZHAOMIAN , GAL ROBIN L. , MAZZUOCCOLO ANNA , GREENE ELLIS , CALHOUN PETER , BEAULIEU LINDSEY C. , CLEMENTS MARK A. , SHERR JENNIFER , PATTON SUSANA R. , BECK ROY
Published: June 2020

Understanding glucodynamics in youth with T1D during a variety of physical activities (PA) may help guide management customized to type of activity. The present study profiled PA, heart rate (HR) and glycemia in youth participating in 5-day hockey camp. Youth attending the Dskate hockey camp, which includes daily hockey drills (D), a tournament (T), mixed martial arts (MMA) and off-ice activities (O), were invited to participate. Data were collected from wrist-based HR (Garmin vívosmart® 3) and Dexcom G5. Thirty-one youth (age 13±2 yrs; 94% on CSII and all using CGM; BMI percentile 69±21%; insulin dose 42±18U/d; HbA1c 7.7±0.8%; duration of T1D 6±3yrs) participated in this observational study. During the day camp, time in range (70-180mg/dL) was 57±15% (mean±SD), time >180mg/dL was 41±16%, and the median time <70mg/dL was 1.7% (IQR: 1.0-3.6%). Mean glucose levels during the activity fell from onset in D (from 183±79 to 170±74 mg/dL) and MMA (201±77 to 194±67 mg/dL), but rose in T (174±53 to 188±50 mg/dL) and O (172±63 to 178±60 mg/dL). HR was similar across activities (110±12 bpm). In a cohort of motivated youth attending a hockey camp, glucose levels tend to drop during practice and MMA but tend to rise in tournaments and in off-ice activities. Future studies will use similar wearable technologies to examine glucodynamics in a larger observational study of a more diverse sample of youth living with T1D.

Disclosure

M. Riddell: Advisory Panel; Self; Zucara Therapeutics Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Z. Li: None. R.L. Gal: None. A. Mazzuoccolo: None. E. Greene: None. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. L.C. Beaulieu: None. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Cecelia Health. Consultant; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi, T1D Exchange. S.R. Patton: None. R. Beck: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1307-P: Do Youth Want Psychosocial Screenings in Diabetes Clinic? Profiles of Acceptability
Authors: WONG JESSIE J. , HANES SARAH , LANNING MONICA S. , TANENBAUM MOLLY L. , NARANJO DIANA , HOOD KOREY K.
Published: June 2020

Background: Psychosocial screening is recommended and increasingly common, but little is known about youths’ perspectives on screenings.

Methods: One hundred and twenty-four adolescents (57.7% female) ages 12-21 years (M=16.2±2.3) completed routine, clinic-integrated screenings. K-means clustering derived profiles and ANOVA assessed correlates profiles.

Results: Four distinct profiles emerged (Table 1). Profiles varied by depression (F=3.54, p=0.017), diabetes distress (F=3.27, p=0.036), and A1c values (F=4.03, p=0.009). Majority (72.6%) placed high importance on diabetes teams awareness about their emotions and reported no difficulties/discomfort (Embracers). Those uncomfortable with screening (Avoiders) were most depressed and had lowest A1C. Youth who endorsed difficulties with tablet and placed low importance about team awareness about their emotions (Skeptics) had relatively high depression but least diabetes distress. A small fourth group (Strugglers; n=3) must be interpreted with caution due to size. No differences were found for age, gender, diabetes duration/type, race/ethnicity, self-rated global health, or anxiety.

Conclusions: Most youth responded favorably to in-clinic psychosocial screenings. Those less satisfied may have increased mental health risk and may benefit from technical support and an emphasized rationale for screenings.

Disclosure

J.J. Wong: None. S. Hanes: None. M.S. Lanning: None. M.L. Tanenbaum: None. D. Naranjo: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ.
1315-P: Application of Multiplex ECL Assay in Mass Screening for Presymptomatic Type 1 Diabetes
Authors: JIA XIAOFAN , HE LING , MIAO DONGMEI , WAUGH KATHLEEN , FROHNERT BRIGITTE I. , STECK ANDREA , REWERS MARIAN , YU LIPING , GENO RASMUSSEN CRISTY R.
Published: June 2020

Islet autoantibody (IAb) assays for a general population screening should ideally be high-troughput, low-cost, and offer high-sensitivity and high positive predictive value in a low-risk population. The Autoimmunity Screening for Kids (ASK) study has compared the performance of the ’gold standard’ radiobinding assays (RBAs) and a multiplex electrochemiluminesence assay (ECL) in a large unselected pediatric population. Single IAb by RBA but negative by ECL have been previously shown to be low-affinity and of low predictive value for progression to clinical diabetes. From 2017-2019, ASK screened for IAbs 23,400 Colorado children ages 1-17 y. A high-throughput multiplex ECL assay combining IAbs to insulin, GAD and IA-2 in one single well was used in parallel with standard non-multiplex RBAs. At the initial screening with RBA, 3.0% (697/23400) of children were positive for at least one IAb, including 0.4% (98/23400) for multiple IAbs and 2.6% (599/23400) for a single IAb. Among children with ≥2 IAbs, ECL assay results were 89.8% congruent with RBA. In contrast, only 21.5% (129/599 p<0.0001) of children with single IAb by RBA were ECL positive (i.e., high-affinity). During a median follow-up of 0.5 y (range 0.1-2.5 y), 90% (98/109) of children with a single IAb by both RBA and ECL remained persistently positive and 9.2% of those progressed to ≥2 IAbs. In contrast, 74% (242/328, p=0.0003) of children with a single IAb by RBA but ECL negative remained persistently positive; only 1.8% (p=0.001) of those converted to ≥2 IAbs (half became ECL positive). ASK results suggest that applying the ECL assay as the confirmation test may help to remove nearly 80% of subjects with single IAb from further follow-up and monitoring, with little loss of sensitivity. Alternatively, the multiplex ECL could be used as the primary screening tool to leverage its high throughput and low cost, compared to RBAs.

Disclosure

X. Jia: None. L. He: None. D. Miao: None. K. Waugh: None. B.I. Frohnert: None. A. Steck: None. M. Rewers: None. L. Yu: None. C.R. Geno Rasmussen: None.
1316-P: Celiac Disease in Youth with Type 1 Diabetes: Association with Age at Diabetes Diagnosis
Authors: ALVING ERIN , CARLIN KRISTEN , LEE DALE , ROBERTS ALISSA J. , DICKERSON JANE , GORBOUNOVA IRINA , LAW HELENE
Published: June 2020

Background: Children with type 1 diabetes mellitus (T1D) are at increased risk for celiac disease (CD) (4-6% prevalence) and ADA clinical practice guidelines recommend screening all children with T1D for CD annually. A prior study suggests that diagnosis with T1D under age nine years correlates with increased risk for CD.

Aim: Assess the risk of CD by patient age at T1D diagnosis.

Methods: We collected data, including TTG IgA serology and ICD9 codes for T1D and CD from the electronic medical records of patients diagnosed at a single pediatric hospital with T1D between January 1, 2009 and July 31 2017. An unadjusted Cox proportional hazards model was used to assess the risk of celiac disease in patients in two groups: those diagnosed with T1D <9 years of age and those diagnosed with T1D> 9 years of age. Subjects were censored at either: diagnosis with CD, last CD screen if lost-to-follow-up, or December 29, 2017. We determined CD diagnosis by ICD9 code.

Results: In the study period, 2263 patients were diagnosed with T1D with mean (SD) age at diagnosis 10.3 years (4.4). CD was diagnosed in 111 (5%). Mean age of T1D diagnosis for those who also developed CD was 8.6 years (4.5) and for those without CD was 10.3 years (4.3). In patients diagnosed with T1D <9 years 57 (6.7%) developed CD vs. 54 (4.7%) in >9 years. Within one year after T1D diagnosis 58 patients had been diagnosed with CD and the relative risk of CD in patients ≤ 9 years was 1.52 compared to patients > 9 years at T1DM diagnosis (95% CI 0.91, 2.54, p=0.111). Within 2 years of T1D diagnosis, 78 had been diagnosed with CD and the relative risk in patients ≤ 9 years was 1.83 vs. patients > 9 years at T1D diagnosis (95% CI 1.17, 2.86, p=0.008).

Conclusion: Patients <9 years at time of T1DM diagnosis have increased risk of CD within 2 years of initial T1D diagnosis compared to patients >9 years at T1D diagnosis.

Disclosure

E. Alving: None. K. Carlin: None. D. Lee: None. A.J. Roberts: None. J. Dickerson: None. I. Gorbounova: None. H. Law: None.

Funding

Seattle Children’s Hospital
1317-P: Improving Access and Communication through Telehealth for Pediatric Type 1 Diabetes
Authors: RASBACH LISA E. , FREEMARK MICHAEL , PURRINGTON VIRGINIA , GRIFFIS MONA , ANNAS ANGELA , PAGE LAURA C. , HALL RACHEL , BENJAMIN ROBERT
Published: June 2020

Telehealth may positively impact diabetes self-management by increasing contact between patients and providers.

Our diabetes team developed a telehealth intervention to provide insulin adjustments and establish diabetes goals. Eligible youth had T1D, Medicaid insurance, and A1c 9-12%. Participants set goals at quarterly visits. Monthly, participants communicated glucose data with the healthcare team through EMR portal or via phone calls. Youth >10 years completed Diabetes Distress Scale (scores 1-6; higher=greater distress) and Diabetes Empowerment Scale (scores 1-5; higher=greater self-efficacy) at baseline, 6 mo, and 12 mo, while caregivers completed Diabetes Distress Scale for Parents (scores 1-5; higher=greater distress). Satisfaction surveys done at 3 and 12 mo (scores 1-5; higher=greater satisfaction). Baseline and 3 mo data presented. Youth (N=32, 56% male, 53% AA), aged 5-22 (12.4±3.9), with T1D for 5.1±3.5 years had baseline mean A1c 10.7±1.5%; 19% CSII and 34% CGM. At baseline, participants endorsed low levels of diabetes distress (mean score 1.9±0.9 youth and 2.1±0.6 parents). Youth endorsed high diabetes self-efficacy at baseline (mean score 4.2±0.6). There was no difference between mean A1c at baseline and 3 months (10.7% to 10.9%, N=26). Baseline A1c did not correlate with age, T1D duration, diabetes distress or empowerment for youth but correlated negatively with parental frustration [“I am the only one who takes responsibility for helping my teen manage diabetes” (r=-0.458; p=0.048) and “my teen ignores my suggestions about diabetes” (r=-0.842; p<0.009)]. Participants reported high satisfaction with the intervention (mean score 4.3±0.49).

Correlation between A1c and parental frustration suggests need to improve communication between T1D teens and caretakers and enhance mental health support. Although A1c did not decline short term, families reported high satisfaction. Further research needs to assess the long-term impact of telehealth interventions.

Disclosure

L.E. Rasbach: None. M. Freemark: None. V. Purrington: None. M. Griffis: None. A. Annas: None. L.C. Page: None. R. Hall: None. R. Benjamin: None.

Funding

Duke University School of Medicine (3993054)
132-OR: Peripheral Serotonin Regulates Dietary Fat Absorption and Intestinal Chylomicron Production
Authors: RAKA FITORE , ADELI KHOSROW
Published: June 2020

Introduction: Diabetic dyslipidemia is a key feature of insulin resistance and is characterized by overproduction of chylomicron particles by the intestine. Chylomicron output can be regulated by hormones secreted from the intestine. Enterochromaffin cells are specialized enteroendocrine cells that secrete serotonin (5-HT). Gut-derived 5-HT is emerging as a regulator of systemic energy homeostasis by regulating adipose and liver lipid metabolism. Currently, the role of 5-HT on intestinal fat absorption and chylomicron production remains unknown. We hypothesize that 5-HT regulates postprandial intestinal fat absorption and chylomicron production.

Methods/Results: Syrian golden hamsters underwent jugular cannulation surgery. The next day, hamsters received an oral fat load (200μl olive oil) followed by intravenous infusion of Triton WR-1339 to prevent lipoprotein clearance. Blood samples were collected prior to and up to 6 hours post fat load. Triglyceride-rich lipoproteins (TRL) which includes chylomicrons were isolated from plasma by density gradient ultracentrifugation and triglyceride (TG) content in this fraction was measured using an enzyme based colorimetric assay. Intravenous administration of 5-HT (1mg/kg) 5 minutes prior to oral fat load increased the rate of plasma TG and TRL-TG accumulation while higher doses of 5-HT (5 and 10mg/kg) produced a transient decrease in plasma TG and TRL-TG accumulation. Treatment with 5-HT4 receptor agonist, Bimu-8 (1mg/kg), increased plasma TG and TRL-TG accumulation. Endogenous 5-HT depletion by para-chloro-phenylalanine (PCPA), an inhibitor of 5-HT synthesis, reduced the rate of TG and TRL-TG accumulation compared to vehicle controls. Furthermore, enhancing 5-HT action by inhibiting 5-HT reuptake with fluoxetine increased the rate of TG and TRL-TG accumulation.

Our results demonstrate that 5-HT is a key regulator of postprandial lipoprotein metabolism and could have important implications for diabetic dyslipidemia.

Disclosure

F. Raka: None. K. Adeli: None.

Funding

Canadian Institutes of Health Research (967131)
1320-P: Building Trust between Researchers and African American and Latino Families of Children with T1D to Enhance Recruitment, Retention, and the Relevance of Research
Authors: BUTLER ASHLEY , HILLIARD MARISA E. , FEGAN-BOHM KELLY , HENDRIX KRISTEN , KARAVITI LEFKOTHEA
Published: June 2020

Background: African American and Latino children with type 1 diabetes (T1D) have persistent disparities in diabetes outcomes. Diabetes outcomes can be significantly improved through behavior change interventions. However, existing behavioral family interventions for T1D have almost exclusively been implemented and evaluated among samples comprised of primarily non-Latino white families because of obstacles to building trust in studies. Challenges to building trust include relatively low percentages of youth with T1D compared to non-Latino whites, and aspects of the academic environment. Identifying and implementing strategies to build trust with minority communities will improve representation in behavioral intervention research.

Methods: We describe methods used to improve recruitment and retention in an ongoing pilot randomized control trial for parents of 60 African American and Latino children. Our community-engaged approach included consultation with culturally-informed communications experts, partnering with community resources (e.g., Health Department and Cooperative Extension Program), and engaging a family advisory board to advise on study branding, recruitment methods, and intervention components. We developed and implemented community information sessions about the study and a “T1D Research and Education Day Event” to launch recruitment. We conducted in-person recruitment visits within a diabetes care center.

Results: Six parents joined the advisory board. Six families attended the informational events. To date, 51 families have consented to participate in the study: 89% of the 8 eligible families in attendance enrolled at the launch event, and 66% of 67 approached in clinic enrolled (68% overall enrollment rate).

Conclusions: Innovative methods for building trust with African American and Latino families have increased engagement compared to previous T1D behavioral research.

Disclosure

A. Butler: None. M.E. Hilliard: None. K. Fegan-Bohm: None. K. Hendrix: None. L. Karaviti: None.

Funding

National Institutes of Health (1DP3DK113236)
1324-P: GLP-1 Hypersecretion in Gestational Diabetes
Authors: FRITSCHE LOUISE , HENI MARTIN , ECKSTEIN SABINE S. , WINZENRIED MAREN J. , HUMMEL JULIA , BIRKENFELD ANDREAS L. , PREISSL HUBERT , HAERING HANS-ULRICH , PETER ANDREAS , FRITSCHE ANDREAS , WAGNER ROBERT
Published: June 2020

Background and Aims: Incretins are crucial for an adequate insulin secretion in response to ingestions of nutrients. In patients with diabetes, prediabetes or a specific genetic background, this incretin effect is blunted. Data on incretin secretion and action during pregnancy are scarce. Here we investigated the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes.

Methods: Pregnant women from the ongoing PREG study underwent 5-point OGTT with 75 g glucose. We measured plasma glucose, insulin and C-peptide at all time points and total GLP-1 at minute 0, 30 and 120. Indices of insulin secretion and GLP-1 increase were calculated from the difference at min 0 and 30. We used linear regression to analyze the relation of GLP-1 and glucose with insulin secretion.

Results: We examined 163 women during gestational week 26.8 (±2.0 SD), GDM was present in 30 (18.4%) women. Insulin secretion was significantly lower in women with GDM (p=0.04, adjusted for BMI, age, week of gestation, insulin sensitivity). GLP-1 levels increased after glucose intake with a peak at 30 min. GLP-1 levels at minute 30 and AUCGLP-1 was significantly higher in women with GDM (by ∼20%, both p=0.03, adjusted for age, BMI and week of gestation). The GLP-1 increase was associated with insulin secretion only in GDM, but not in women with normal glucose tolerance. This association remained significant even after adjustment for increase of glucose and basal insulin levels (GDM group: p<0.001, non GDM: p=0.69).

Conclusion: Women with GDM had lower insulin secretion despite increased GLP-1 levels during OGTT. The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. In addition to incretin resistance, this phenomenon suggests a dysfunction of glucose stimulated insulin secretion.

Disclosure

L. Fritsche: None. M. Heni: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S. S.S. Eckstein: None. M.J. Winzenried: None. J. Hummel: None. A.L. Birkenfeld: None. H. Preissl: None. H. Haering: None. A. Peter: None. A. Fritsche: None. R. Wagner: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company.

Funding

German Federal Ministry of Education and Research (01GI0925)
1326-P: Maternal HbA1c in Pregnancy Is Associated with Higher Placental DNA Methylation at CTNNA3
Authors: JUVINAO-QUINTERO DIANA L. , CARDENAS ANDRES , BOUCHARD LUIGI , PERRON PATRICE , HIVERT MARIE-FRANCE
Published: June 2020

Adverse perinatal outcomes have been associated with exposure to maternal hyperglycemia during pregnancy, which can be assessed by glycated hemoglobin A1c (HbA1c) levels. Prior analyses in the Gen3G cohort revealed that maternal HbA1c measured at the 2nd rather than at the 1st trimester, was strongly associated with differences in DNA methylation in fetal tissues. Thus, in this study, we seek to identify novel epigenetic mechanisms of placental response to prolonged exposure to maternal hyperglycemia by conducting an Epigenome-Wide Association Study (EWAS) of maternal HbA1c measured at 2nd trimester and DNAm of full-term placentas in 448 mother-child pairs of the Gen3G cohort. We tested associations at 791,131 CpG sites, adjusting for age, gestational age, week at HbA1c measurement, gravidity, smoking, pre-pregnancy BMI, sex, and the first ten principal components from ReFACTor to account for cell-type admixture. We also examined consistency in the direction of associations between maternal 2nd trimester HbA1c, and 1st trimester HbA1c for top CpGs detected in EWAS at p<10-7. We further investigated causality of CpGs with the smallest p-value in the EWAS using Mendelian Randomization (MR). In EWAS, we observed with Bonferroni significance (p<6.3x10-8) the association between maternal HbA1c (per %-unit) and higher placenta DNAm at cg23886783 mapping to the SLC20A1 gene (effect=0.9%, 95% CI= 0.5% to 1.2%, p=6.1x10-8). No other CpG was observed with Bonferroni or FDR significance in the EWAS. In addition, we found consistency in the direction of associations between HbA1c measured at 1st trimester and placental DNAm for the top six CpGs with the smallest p-value discovered in the EWAS of 2nd trimester HbA1c. Among these top six CpGs, we found nominal evidence that maternal HbA1c was causally associated with higher DNAm at cg11963170 in CTNNA3 (MR effect=25.1% per 1 %-unit, 95% CI= 3.1% to 47%, p=0.04). Our findings help to reveal placental adaptations to long-term maternal hyperglycemia.

Disclosure

D.L. Juvinao-Quintero: None. A. Cardenas: None. L. Bouchard: None. P. Perron: None. M. Hivert: None.

Funding

American Diabetes Association (1-15-ACE-26 to M-F.H.)
1328-P: Infant Mesenchymal Stem Cell Insulin Sensitivity Is Associated with Maternal Plasma-Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study
Authors: CHAVES ALEC B. , JOHNSON JONATHAN A. , ZHENG DONGHAI , DABELEA DANA , HOUMARD JOSEPH A. , BOYLE KRISTEN E.
Published: June 2020

Introduction: Maternal obesity is associated with greater neonatal adiposity and increased offspring risk for type 2 diabetes (T2D) later in life. We have previously reported that mesenchymal stem cells (MSCs) isolated from umbilical cord tissue maintain similar metabolic phenotype to the infant, particularly when differentiated to adipocytes or myocytes. A well-established driver in the pathogenesis of T2D is skeletal muscle insulin resistance. Therefore, we hypothesized that MSCs from infants born to mothers with obesity would display insulin resistance when differentiated to myocytes.

Objectives: The objective was to determine the effect of maternal obesity on offspring MSC insulin sensitivity (Si).

Methods: MSCs were isolated from umbilical cord tissue from offspring born to either normal weight (BMI 21.1 ± 0.9, n = 9) or obese (BMI 32.9 ± 2.1, n = 10) mothers enrolled in the Healthy Start pre-birth cohort study in Colorado. Following differentiation into skeletal muscle myocytes, MSCs were serum starved and incubated with 14C-glucose, in the presence or absence of insulin. The rate of insulin-mediated 14C-glucose incorporation into glycogen, was used as an index of offspring Si.

Results: Offspring Si did not correlate with maternal BMI (r = 0.26), nor was BMI different between groups when median-stratified by offspring Si. However, maternal free fatty acid levels positively correlated with offspring Si (r = 0.63, p < 0.05) and were significantly elevated in the high Si group (low Si vs. high Si; 332.1 ± 30.9 vs. 483.3 ± 48.7 uEq/L, p < 0.05).

Conclusions: Offspring Si was not related to the BMI of the mother. Moreover, offspring Si was higher in cells from infants born to mothers with higher free fatty acids during pregnancy. Considering the role of insulin in somatic growth pathways, this phenomenon may serve to increase available nutrient storage capacity during early development.

Disclosure

A.B. Chaves: None. J.A. Johnson: None. D. Zheng: None. D. Dabelea: None. J.A. Houmard: None. K.E. Boyle: None.

Funding

American Heart Association (14PRE18230008); Nutrition Obesity Research Center (P30DK048520); National Institutes of Health (R01DK076648); Colorado National Center for Advancing Translational Sciences (UL1TR001082)
133-OR: Dyrk1b Is a Nutrient-Sensing Protein That Triggers De Novo Lipogenesis by Activating mTORC2 Complex: Implication for the Treatment of Type 2 Diabetes
Authors: BHAT NEHA
Published: June 2020

The mechanisms underlying enhanced insulin-induced de novo lipogenesis (DNL) in an insulin resistant liver are not understood. Genetic studies in subjects with inherited metabolic syndrome, a cluster of phenotypes that includes dyslipidemia, glucose intolerance, central obesity and insulin resistance led to the identification of perfectly segregating mutations in the Dyrk1b gene. This work also revealed previously unknown function of Dyrk1b in glucose and lipid metabolism. In this study, we introduce Dyrk1b as the missing link between enhanced HGP and increased DNL. The liver specific Dyrk1b knockdown protected against hepatic steatosis, hyperlipidemia and diet induced insulin resistance, while AAV mediated Dyrk1b elevation enhanced DNL causing hepatic steatosis, hyperlipidemia and augmented hepatic Glucose Production (HGP), features characteristic of diabetic dyslipidemia. A comprehensive analysis revealed that Dyrk1b facilitates DNL by binding and activating the mTORC2 complex in a kinase independent fashion. Mechanistically, Dyrk1b displaces mTORC2 inhibitor Fkbp12 from the complex and induces auto-phosphorylation of the mTOR protein. Accordingly, the knockout of mTORC2 function, rescued hepatic steatosis, inflammation, and hyperlipidemia. The global relevance of this disease pathway is illustrated by increased hepatic Dyrk1b levels in mice and humans with hepatic steatosis. Altogether, our findings reveal Dyrk1b as a nutrient sensing protein that triggers DNL and hepatic insulin resistance and is an attractive therapeutic target for type 2 diabetes.

Disclosure

N. Bhat: None.

Funding

National Institutes of Health (RHL135767A, P30DK034989)
1333-P: The Adipokine Fatty Acid Binding Protein 4 Promotes Glucose Production in Gestational Diabetes Mellitus
Authors: MADAH RAGAD , RONEN IDIT RON , RATHAUS MORAN , ZEMET RONI , TOVI SHALI AMAZAKI , TIROSH AMIR
Published: June 2020

Gestational diabetes mellitus (GDM) is characterized by maternal hyperglycemia and insulin resistance that develops during pregnancy. Altered secretion of adipokines that modulate insulin action during pregnancy has been implicated in GDM pathogenesis. FABP4 is an adipokine with an important role in promoting insulin resistance in various animal models. In humans, FABP4 was suggested to regulate systemic metabolism. Although elevated levels of circulating FABP4 were demonstrated in GDM, its differential contribution to GDM pathophysiology is unclear. In this study, we aimed to determine the tissue source of elevated circulating FABP4 levels and to assess FABP4 differential contribution in promoting hepatic glucose production in GDM. We included 71 pregnant women defined as normal glucose tolerant (NGT) and 31 diagnosed with GDM. Maternal level of FABP4 before delivery was measured using ELISA. FABP4 circulating levels were increased in GDM compared to NGT (14.1 IQR: 11.5-21.4 ng/ml vs.10.3 IQR: 6.6-12.4 ng/ml, respectively, p=0.0014), with a rapid post-partum decline in FABP4 levels observed in both groups. Using biopsies of placenta, sub-cutaneous (sWAT) and visceral (vWAT) adipose tissues, we observed that FABP4 is secreted from these tissues during pregnancy. FABP4 secretion from vWAT of GDM women was ? 2 fold higher than that of NGT women. Depletion of FABP4 from vWAT conditioned media of NGT or GDM women using monoclonal antibodies, significantly suppressed glucose production in primary hepatocytes by ? 20% and ? 36%, respectively (p<0.05). Taken together, our data highlight the importance of FABP4 in the pathophysiology of enhanced hepatic glucose production in GDM.

Disclosure

R. Madah: None. I. Ron Ronen: None. M. Rathaus: None. R. Zemet: None. S. Amazaki Tovi: None. A. Tirosh: Advisory Panel; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; DreaMed Diabetes. Research Support; Self; Medtronic.

Funding

Israeli Diabetes Association
1336-P: Trimethylamine N-Oxide Inhibits the Formation of Neutrophil Extracellular Traps to Regulate Placental Development in Gestational Diabetes Mellitus
Authors: LIN XIAOJING , HE XIAOLING , XIAO XIAOQIU
Published: June 2020

Objective: Trimethylamine N-oxide (TMAO) is associated with risk of gestational diabetes mellitus (GDM), and TMAO levels in peripheral/cord blood of GDM mothers increased. Diabetes primes neutrophils to produce neutrophil extracellular traps (NETs), but it has not been reported in GDM. We determined the relationship between NETs and GDM, and explored potential role of TMAO.

Methods: Maternal peripheral blood was collected during OGTT tests, and cord blood and placenta were collected during delivery. Plasma concentrations of cell-free double-stranded DNA (dsDNA) were compared between GDM and control mothers and association analysis was performed. Expression of myeloperoxidase (MPO) in placental tissues of GDM and control mothers was examined. Neutrophils from the blood of healthy donors were used to observe effects of TMAO on NETs formation. The effect of TMAO on human placental extravillous trophoblast cell line HTR-8/Svneo was examined.

Results: Compared with controls, plasma concentrations of dsDNA in peripheral blood and cord blood were significantly increased in GDM mothers. Association analysis found that concentrations of dsDNA in peripheral and cord blood plasma were positively correlated with BMI and blood glucose levels, but not blood pressure. In addition, the placental thickness was positively correlated with dsDNA levels in cord blood plasma. MPO expression in the placental tissues of GDM mothers was also significantly higher than that of control mothers. TMAO-treated neutrophils could resist the formation of NETs stimulated by PMA or LPS, and TMAO promotes the proliferation, migration, invasion and angiogenesis of the cells.

Conclusion: The formation of NETs was increased in GDM, and was positively correlated with BMI and blood glucose. TMAO could inhibit NETs formation and promote invasion and angiogenesis of human placental trophoblast cells, which may be involved in the development of the placenta.

Disclosure

X. Lin: None. X. He: None. X. Xiao: None.