bluuebunny/crossref_metadata_2025_split huggingface dataset:
87-OR: Vitreous Retinol Binding Protein 3 Is Increased in Patients without Advanced Diabetic Retinopathy in Type 1 and Type 2 Diabetes
Authors: FICKWEILER WARD , PARK HYUNSEOK , PARK KYOUNGMIN , BOUMENNA TAHANI , GAUTHIER JOHN , WU I-HSIEN , CAVALLERANO JERRY D. , AIELLO LLOYD P. , SUN JENNIFER , KING GEORGE L. 
Published: June 2021

Retinol Binding Protein 3 (RBP3), a retinol transport protein secreted mainly by photoreceptors, may inhibit progression of diabetic retinopathy (DR) by decreasing glucose uptake and inflammation in the retina. In people with type 1 diabetes with duration of ≥50yrs (Joslin Medalist Study), &gt;40% of Medalists exhibited no to mild non-proliferative diabetic retinopathy (NPDR) and increased expression of RBP3 compared to those with severe DR. We examined 213 vitreous samples from a larger population of Medalists and patients with type 1 and type 2 diabetes with shorter diabetes duration (mean±SD 26.5±12.7 years) from the Joslin Beetham Eye Institute to determine whether vitreous RBP3 levels are correlated with DR severity and progression in a broad population with diabetes. RBP3 was increased in vitreous from people with no diabetes compared to subjects with type 1 and type 2 diabetes (p&lt;0.0001). Type of diabetes (type 1 vs. type 2, p=0.44) and A1c (p=0.68) were not associated with RBP3. In patients with both type 1 and 2 diabetes, vitreous RBP3 levels gradually decreased from the highest concentration in no to mild NPDR (15.7 nM) to the lowest concentrations in advanced DR (moderate-severe: 8.2 nM, p=0.01 vs. no-mild NPDR; active proliferative DR: 8.4 nM, p=0.0003 vs. no-mild NPDR; quiescent proliferative DR: 3.5 nM, p&lt;0.0001 vs. no-mild NPDR). RBP3 was higher in moderate-severe NPDR compared to quiescent PDR (p=0.03). RBP3 concentrations in surgical samples from living donors were lower than those from post-mortem Medalists (p&lt;0.01), but were associated with DR severity in both groups (p=0.03 and p&lt;0.0001, respectively). Increased RBP3 concentrations were associated with reduced risk of PDR development over time (n=34, p&lt;0.001). These findings indicate that elevated vitreous RBP3 is associated with decreased DR severity and decreased risk of PDR development, supporting the postulate that RBP3 is a protective factor and therapeutic target for the progression of DR.

Disclosure
W. Fickweiler: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc. H. Park: None. K. Park: None. T. Boumenna: None. J. Gauthier: None. I. Wu: None. J. D. Cavallerano: None. L. P. Aiello: Consultant; Self; KalVista Pharmaceuticals, Novo Nordisk, Regeneron Pharmaceuticals Inc., Stock/Shareholder; Self; KalVista Pharmaceuticals. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma.

Funding
National Eye Institute (R01EY026080-01); National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK094333-01); JDRF (17-2013-310); Beatson Foundation; Dianne Nunnally Hoppes Fund
871-P: Integrating the PHQ-A Depression Screening Tool within the Electronic Health Record Increases Detection of Depression Symptoms
Authors: GETTINGS JULIE , PATIL OONA , VAJRAVELU MARY ELLEN , HAWKES COLIN P. , TUTTLE ALAN , BUZBY MARIANNE , CREAN STEPHANIE , DEVER MAUREEN B. , MULLIGAN LIAM , WILLI STEVEN M. 
Published: June 2021

Depression symptoms are common for youth with diabetes and may negatively affect quality of life and health outcomes. In our large, urban, pediatric diabetes clinic, depression screening with a condensed, verbally-administered measure, the Patient Health Questionnaire-2 (PHQ-2), had a positivity rate of only 2%, which is far below anticipated rates. We developed a quality improvement project to increase the sensitivity of depression screening for youth with diabetes. The primary test of change was electronically administering the Patient Health Questionnaire for Adolescents (PHQ-A), a 13-question survey validated for use in pediatrics. Youths ≥ 12 years of age were asked to privately complete the PHQ-A on a laptop at a diabetes visit annually. Responses populated within the electronic health record, and medical providers were trained to respond to positive screens with the support of a social worker or psychologist. A run chart was used to assess screen-positivity rate over time; ≥6 points above the baseline was considered a significant change. During the study period (August 2018—February 2020), 740 PHQ-A screens were completed by 618 patients. The majority of patients (n = 489; 79%) had type 1 diabetes, 50% were female, and the median age (IQR) at screening was 16.2 (14.0-18.0) years. On average, 38.9 screens/month were completed (range: 16-70), and 6.8 screens/month were positive (range: 0-16). Of all completed screens, 129 (17.4%) were positive. The positivity rate was greater than baseline for all 7 quarters evaluated after implementation of PHQ-A. Of the positive screens, 55 (43%) were positive due only to SI or SA history. Using a standardized and easily administered approach, the detection of depression symptoms increased to a range comparable to previous reports. The number of completed screens per month was manageable, allowing us to promptly address depression symptoms within our interdisciplinary clinic workflow.

Disclosure
J. Gettings: None. S. M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Medtronic, Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. O. Patil: None. M. Vajravelu: None. C. P. Hawkes: None. A. Tuttle: None. M. Buzby: None. S. Crean: None. M. B. Dever: None. L. Mulligan: None.
889-P: Prescriber Perceptions of the Implementation of Liraglutide into Pediatric Type 2 Diabetes Care
Authors: HITT TALIA A. , DIAZ SANDRA VAZQUEZ , SANCHEZ-KLEINBERG YESENIA , SHEA JUDY A. , KATZ LORRAINE E. , VAJRAVELU MARY ELLEN 
Published: June 2021

Background: In 2019, nearly two decades after metformin approval, liraglutide became the third medication approved by the U.S. FDA for pediatric type 2 diabetes (T2D). However, successful uptake of liraglutide in practice depends on prescribers’ perceptions of acceptability and appropriateness of use in this population.
Objective: We explored pediatric diabetes prescribers’ perceptions on ordering liraglutide, including facilitators and barriers, for youth with T2D at a single, large academic center.
Methods: We conducted semi-structured interviews with diabetes attending physicians (A), fellow physicians (F), and nurse practitioners (NP) supplemented with a patient vignette, chart-stimulated recall (CSR), and review of a clinical practice guideline (CPG). Interviews were audio-recorded, transcribed, and analyzed using modified grounded theory by three coders with constant comparison techniques.
Results: Nineteen physicians (15 A, 4 F) and 6 NPs with a median experience of 7 years (1.5- 40) participated. Themes identified included 1) primary drivers of use: desire to promote weight loss/maintenance or to avoid/reduce insulin use; 2) acceptance by patients and families: highest for those with familiarity with the medication class and interest in weight benefits; and 3) primary barriers to prescribing: patients’ dislike of injections or prescriber hesitancy due to lack of experience with the drug, concerns about adherence, or issues with insurance coverage. Although most responders recommended liraglutide when presented with a patient vignette, they recalled prescribing barriers in actual practice during CSR. The CPG was endorsed as a facilitator to prescribing, but additional dissemination and use strategies were recommended.
Conclusions: Although liraglutide adds to the toolbox for pediatric T2D, our findings highlight the challenges of introducing new therapeutics and provide insights that may guide implementation efforts in pediatric diabetes clinics.

Disclosure
T. A. Hitt: None. S. Vazquez diaz: None. Y. Sanchez-kleinberg: None. J. A. Shea: None. L. E. Katz: None. M. Vajravelu: None.

Funding
National Institutes of Health (5T32DK063688-17, K23DK125719-01); University of Pennsylvania
9-LB: Effects of Hyperglycemia-Induced Stress in a Human Cardiomyocyte Cell Line
Authors: WAGHELA HIRAL , THAKUR VIKRAM , CHATTOPADHYAY MUNMUN 
Published: June 2021

The prevalence of diabetes in America has continued to increase over the past years, affecting 10.5% of the US population. Cardiomyopathy is one of the major complications of long-term diabetes. Diabetic cardiomyopathy is characterized by an increase in the thickness and rigidity of the heart wall resulting in contractile dysfunction that can ultimately result in heart failure. Hyperglycemia has been also associated with an increase in the production of reactive oxygen species and inflammatory mediators. In the current study, we investigated the role of hyperglycemic exposure to cardiomyocyte in altering the epigenetic markers such as histone deacetylases (HDACs) and inflammatory mediators (such as TLR4 and RAGE) in the progression of cardiomyocyte remodeling and hypertrophy. Cardiac damage was assessed by analyzing the expression of cardiac structural proteins such as Troponin I&T and Connexin43 (Cx43). AC16 cardiomyocyte cell line derived from adult ventricular heart tissue was subjected to high glucose conditions (25 mM) for 24 hours and stress mediated markers were assessed by Western Blot and immunocytochemistry. The statistical significance of the difference between groups was determined by ANOVA (systat 13 software, SPSS Inc., Chicago, IL, USA), using Bonferroni correction for the multiple post hoc analyses for each control and hyperglycemic conditions. An increase in class I HDAC expression (HDAC2) was observed, with no changes seen in the expression of class II HDACs (HDAC 4 and 6). A downregulation of CXCR4 was observed, suggestive of its role as a cardioprotective agent. Increased levels of oxidative stress markers such as RAGE and TLR4 were seen, along with increased expression of markers of cardiac injury such as Cx43 and Troponin I&T. These findings suggest that epigenetic mechanisms and oxidative stress-mediated inflammatory markers can alter the functionality of cardiomyocytes exposed to high glucose conditions.

Disclosure
H. Waghela: None. V. Thakur: None. M. Chattopadhyay: None.

Funding
Texas Tech University Health Sciences Center El Paso (183381SEED)
9-OR: Personalized Diets by Prediction of Glycemic Responses Improve Glycemic Control in Subjects with Newly Diagnosed T2D
Authors: REIN MICHAL S. , BEN-YACOV ORLY , GODNEVA ANASTASIA , SHILO SMADAR , ZELBER-SAGI SHIRA , ELINAV ERAN , SEGAL ERAN 
Published: June 2021

Dietary modifications are crucial for the management of newly-diagnosed type-2 diabetes (T2D) and prevention of its health complications, but many patients fail to achieve clinical goals with diet alone. We previously developed a machine-learning algorithm for predicting personalized postprandial glucose responses (PPGR) to meals using clinical and gut microbiome features, and showed that dietary interventions based on this algorithm successfully lowered PPGRs in adults with prediabetes. Here, we sought to evaluate the clinical efficacy of our algorithm-based diet in subjects with newly-diagnosed T2D. We performed a short-term randomized controlled crossover trial and compared the effects of an algorithm-based personalized postprandial-targeting (PPT) diet, to those of a commonly used Mediterranean (MED) diet on glucose levels in 23 subjects with newly-diagnosed T2D. Average PPGR, glucose fluctuations, daily time of glucose levels &gt;140 mg/dl and fructosamine levels decreased significantly more during the PPT intervention compared to the MED intervention. We further evaluated the long-term clinical effects of the PPT diet in 16 of the participants by an additional 6-month PPT intervention, and found significant improvements in multiple clinical parameters, including HbA1c (mean±SD, -0.39±0.48%, p&lt;0.001), fasting glucose (-16.4±24.2 mg/dl, p=0.02), fasting insulin (-2.3±4.0 MCU/ml, p=0.04), triglycerides (-49±46 mg/dl, p&lt;0.001), body weight (-3±3.5 kg, p=0.005), body fat% (-2.5±3%, p=0.005) and waist circumference (-4.7±3.7 cm, p=0.001). Importantly, 61% of the participants exhibited diabetes remission at the end of the intervention, as measured by HbA1c. Finally, some of the improvements in clinical outcomes were accompanied by significant alterations to the gut microbiome composition. These findings may be valuable for the design of future studies in larger cohorts and may have implications for dietary advice in clinical practice.

Disclosure
M. S. Rein: None. O. Ben-yacov: None. A. Godneva: None. S. Shilo: None. S. Zelber-sagi: None. E. Elinav: Consultant; Self; BiomX, DayTwo. E. Segal: Consultant; Self; DayTwo.
901-P: COVID-19 and Type 2 Diabetes: Children Spared from Severe Disease Course
Authors: CYMBALUK ANNA , ASTUDILLO MARCELA , DESALVO DANIEL , BACHA FIDA , MCKAY SIRIPOOM , REDONDO MARIA J. 
Published: June 2021

Diabetes and hyperglycemia are risk factors for severe COVID-19 course and/or death in adult patients. While most cases in children remain mild, studies in pediatric T2D are limited.
Our study aim was to describe the clinical characteristics of COVID-19 course in youth with T2D. We conducted a retrospective review of electronic medical records of patients with T2D and positive SARS-CoV-2 PCR testing performed at Texas Children’s Hospital between 3/1/2020 and 10/31/2020. Demographics, diabetes treatment regimen, metrics of glycemic control, and variables of COVID-19 course were recorded and analyzed.
We identified 14 youth with active T2D and positive SARS-CoV-2 testing. All individuals had established diabetes; none were concurrently diagnosed with new onset T2D and SARS-CoV-2. Of them, 43% [n=6] were African-American, 57% [n=8] Hispanic, and none were Non-Hispanic Whites. All individuals had public medical insurance and were obese, with mean BMI Z score =+2.22 [SD =0.48]. Median last hemoglobin A1C within 3 months prior to testing positive for SARS-CoV-2 was 13.2% [IQR= 2.50%], with 27% [n=3] patients’ last A1C above the limit of detection [&gt;14.0%] and 91% [n=10] above the American Diabetes Association Standards of Care goal of 7.0%. Twelve (85.7%) children were on insulin and 36% [n=5] on Metformin. Admission was required in 42.8% [n=6] children, 1 prior and 2 after having SARS-CoV-2 detected, and 3 at the time of SARS-CoV-2 detection for diabetic ketoacidosis [DKA]. Mean pH for those admitted for DKA [n=3] was 7.12 [SD = 0.09]. Median length of all admissions was 1.5 days [IQR = 1.23 days]. One patient required brief supplemental oxygen for comfort, but no patients had documented hypoxia. No patients required intubation and no patients expired.
In sum, T2D in youth did not appear to be a risk factor for severe SARS-CoV-2 related illness. However, prevalence of DKA was higher than expected, suggesting that COVID-19 may adversely affect diabetes course; this will require further investigation.

Disclosure
A. Cymbaluk: None. M. Astudillo: None. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. F. Bacha: None. S. Mckay: None. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc.
923-P: Tolerability and Time-Action Profile of Technosphere Insulin in Pediatric Subjects
Authors: JONES MARISA C. , HALLER MICHAEL J. , NG SAVANNAH E. , BHAVSAR SUNIL , KAISERMAN KEVIN B. , KRUEGER JOHN A. 
Published: June 2021

Introduction: Technosphere Insulin (TI) is an inhaled ultra-rapid-acting dry powder prandial insulin. Reported are the results of the first study of TI in pediatric patients.
Methods: PK/PD and safety of TI was evaluated in a single-arm, 4-week study in 30, 8-17 years old subjects with T1DM on a stable MDI regimen, meeting pre-defined pulmonary function testing criteria. On day 1, subjects received an individualized single prandial dose of TI (4-16 U, in 4U increments) based on their usual meal-time dose and meal content. Serum insulin and blood glucose were measured -30 to 250 minutes relative to dosing. Over the next 4 weeks, each subject’s dose of TI was titrated, targeting a 120-150 minute post-prandial glucose level of 110-180 mg/dL. Safety and tolerability were assessed over the course of the study. Severe hypoglycemia was defined as an event associated with coma, loss of consciousness, or seizure.
Results: Mean age of subjects was 12.7 years (60% Female; 83.3% White). Serum insulin rapidly increased post-dose and returned to baseline by 120 minutes. Mean serum insulin Cmax was 77.3 µU/ml, 119.15 µU/ml, 101.29 µU/ml and 104.86 µU/ml for doses of 4, 8, 12 and 16U respectively. Tmax occurred at 10.5, 13.9, 14.6, and 20.0 minutes post-dose for 4, 8, 12 and 16U respectively. Glucose lowering during 30-60 minutes post-dose was consistent with the PK profile. Over 4 weeks of study, 23 subjects (76.7%) reported 41 TEAEs. One subject had an SAE of diabetic ketoacidosis that was considered possibly related to TI. The most common AEs were hypoglycemia (none severe) and cough. No subjects had a clinically relevant decline in pulmonary function.
Conclusion: Inhaled TI demonstrated an ultra-rapid time-action profile similar to that observed in adults. These data suggest TI can be safely administered to children and adolescents ages 8-17 with T1DM.

Disclosure
M. C. Jones: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; MannKind Corporation. M. J. Haller: Board Member; Self; SAB Biotherapeutics, Inc., Consultant; Self; MannKind Corporation, Other Relationship; Self; Janssen Pharmaceuticals, Inc., Sanofi. S. E. Ng: Employee; Self; MannKind Corporation. S. Bhavsar: Employee; Self; MannKind Corporation. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. J. A. Krueger: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; Eli Lilly and Company.

Funding
MannKind Corporation
926-P: HbA1c Monitoring among Adolescents and Young Adults with Type 1 Diabetes: Impact of Diabetes Care Provider Type
Authors: WISK LAUREN E. , LANDRUM MARY BETH , FU CHRISTINA , CHIEN ALYNA 
Published: June 2021

Adolescents and young adults with type 1 diabetes (T1D) are at-risk of not receiving the recommended levels of annual HbA1c testing, but extent to which this occurs and the degree to which this may due to not accessing care or changes in physicians is poorly understood. This is an observational study of 9,916 unique 13-26 year olds with T1D who were continuously insured by a large US health insurer for 12 months or more during 2012-2016. We evaluate the frequency at which this population does not receive twice yearly HbA1c tests and the degree to which such rates are associated with age, not accessing care at all, and types of physicians of delivering diabetes care descriptively and using multivariable regression. The percent of those with T1D not receiving twice yearly HbA1c tests rose from 17% to 40% between the ages of 13 to 26 (peaked at 45% at age 24). The percent not making any diabetes visit within a year rose from 12% to 17% between those same ages. Pediatric endocrinologists and general pediatricians were the dominant providers at age 13 (62% and 26%, respectively), while adult endocrinologists and adult primary care physicians were the dominant providers at age 26 (48% and 44%, respectively). The age at which care transfers from pediatric to adult physicians appears to be at age 18 for primary care and at age 19 for endocrinologists. Receiving the twice yearly HbA1c tests was associated with endocrinologists after adjusting for sex, age, rurality, and neighborhood poverty. HbA1c monitoring declines substantially as adolescents grow into adults and appears to be related to not accessing healthcare despite being insured and also be due to transferring from pediatric to adult primary care physicians and endocrinologists.

Disclosure
L. E. Wisk: None. M. Landrum: None. C. Fu: None. A. Chien: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K01DK116932 to L.E.W.); Agency for Healthcare Research and Quality (U19HS024072 to A.C.)
933-P: Impact of Sleep and Activity on Glycemic Control and Quality of Life in Haitian Youth with Type 1 Diabetes
Authors: BABINSKI MELANIE , DUPERVAL REGINA , VON OETTINGEN JULIA E. , ALTENOR KETLY 
Published: June 2021

Background: Sleep and exercise affect overall health. In youth with type 1 diabetes (T1DM), physical activity and adequate sleep reportedly improve glycemic control. Data from low-income countries is lacking.
Objective: To describe sleep and activity in Haitian youth with T1DM and examine their impact on glycemic control, health-related quality of life (HRQL) and Life Satisfaction (LS).
Methods: Single-center cross-sectional study in Haiti, including youth diagnosed with T1DM between 0-25 years old. Wristbands tracked activity and sleep for 10 days. Diabetes Quality of Life in Youth (DQoLY) questionnaire was used to evaluate HRQL and LS. Point-of-care hemoglobin A1c (A1C) values (max. measure 14%) were recorded. Linear regression was used to assess sleep and activity as predictors of A1C, HRQL and LS.
Results: We included 66 participants (59% female, mean age 17.8±4.8 years, mean diabetes duration 3.7±3.4 years, mean BMI Z-score -0.86±1.1). Mean HRQL was 63/100 and mean LS 65/100. Mean A1C was 11.3%, and 22 patients (34%) had A1C &gt;14%. Mean daily step count was 9448±8431 and mean sleep duration 7h31±1h17. Higher A1C was predicted by younger age (p=0.005) and lower BMI Z-score (p=0.0016), but not sex or diabetes duration. Better HRQL was predicted by younger age (p=0.029), and marginally by male sex (p=0.07). None predicted LS. Sleep duration and step count did not predict either outcome. When excluding patients with A1C&gt;14% (to eliminate a possible ceiling effect), shorter sleep duration was a significant predictor of higher A1C (p=0.03) in uni- and multivariate models adjusted for age, sex, BMI and diabetes duration.
Conclusions: Youth with T1DM in Haiti have poor glycemic control, and low HRQL and LS. Their average sleep duration and daily activity is similar to reported values in peers. While activity level did not affect A1C, HRQL or LS, shorter sleep duration predicted higher A1C in youth with A1C&lt;14%. Prospective studies with larger sample sizes are needed to validate our findings.

Disclosure
M. Babinski: None. R. Duperval: None. J. E. Von oettingen: None. K. Altenor: None.