bluuebunny/crossref_metadata_2025_split huggingface dataset:
591-P: Feasibility of Implementing Point-of-Care Diabetic Retinopathy Screening into the Workflow at a Pediatric Diabetes Clinic
Authors: WOLF RISA M. , THOMAS CHRYSTAL G. , ALVIN LIU T. Y. , CHANNA ROOMASA 
Published: June 2019

Background: The prevalence of diabetic retinopathy (DR) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) is 5.6% and 9.1%, respectively. The ADA recommends yearly screening for DR. Only two-thirds of youth with diabetes receive their annual dilated eye exam. In order to save time off from school/work for our patients and their families, we implemented point of care (POC) diabetic retinopathy screening in our pediatric diabetes clinic. We studied the impact on workflow, imaging time, and operator experience.
Methods: As part of a larger prospective longitudinal study, we measured the implementation of DR screening and its impact on workflow, imaging time, and analyzed the camera operator learning curve.
Results: We screened 39 youth with diabetes, average age 11.46y (range 6-17y). 35 (89%) had T1D, 4 (11%) had T2D. Patients were imaged without pharmacological dilation after their multidisciplinary diabetes team visit, or during a break between providers. Imaging was performed by a technician with no prior background in ocular imaging. Average imaging time was 7min14sec (SD 2.55, range 3.5-16.66). Analysis of technician operator learning curve showed average imaging time of 7min45sec for first 20 cases, compared to 6min44sec for second 19 cases. Images of readible quality were obtained with 1 attempt in 75%, and with 2 or more attempts in 25% of patients. All patients were able to be imaged.
Conclusions: The use of a non-mydriatic fundus camera for diabetic eye screening in pediatrics is feasible, even in young children. It takes very little time, and requires minimal operator training. The overall rates of DR are low in children, and POC DR screening improves adherence to ophthalmic screening guidelines, and saves time off from school/work for diabetes youth and their families.

Disclosure
R.M. Wolf: None. C.G. Thomas: None. T. Liu: None. R. Channa: None.

Funding
Johns Hopkins Children's Center
594-P: Homocysteine as a Predictor for Diabetic Retinopathy Risk and Management
Authors: TAWFIK AMANY M. , MOHAMED RIYAZ , ALHUSBAN SUHIB , CHU SUNG MIN , KHALIL ABRAHAM Q. , BARTOLLI MANUELA , AL-SHABRAWEY MOHAMED 
Published: June 2019

Diabetic retinopathy (DR) is one of the most significant microvascular complications of diabetes mellitus (DM) and is the most common cause of blindness in people under the age of 65. The ability to accurately predict patient susceptibility and prognostic implications of the disease is essential to its optimal management. Unfortunately, the current screening process for DR restricts the population that can be evaluated and the disease goes undetected until irreversible damage occurs. Therefore, a reliable and inexpensive screening process for DR would greatly increase the number of patients that can be evaluated and identify individuals in the early stages of DR in need of further assessment and treatment. Our previous work has shown that elevated blood homocysteine (Hcy) levels disrupted blood retinal barrier integrity, induced retinal ischemia and neovascularization, activated endoplasmic reticulum and oxidative stress pathways and induced epigenetic modifications in the retina. The current study aimed to evaluate Hcy as a biomarker in DR screening. Hcy levels were measured by ELISA and immunolocalization methods in serum, vitreous and retina of diabetic patients as well as in serum and retina of different animal models of DM representing type 1 diabetes (T1DM) (STZ mice, Akita mice and STZ rats) and db/db mice which exhibit features of human type 2 diabetes (T2DM). Our results revealed increased Hcy levels and immunostaining in serum, vitreous and retina of diabetic patients and experimental animals’ models of diabetes. Moreover, optical coherence tomography (OCT) and fluorescein angiography (FA) were used to evaluate the retinal changes in mice eyes after Hcy-intravitreal injection into the eyes of normal wild type (WT) and diabetic (STZ) mice. Hcy-induced changes in mice retina which were aggravated under diabetic conditions.
In conclusion, our data reported Hcy as a strong candidate for use as a biomarker in DR screening. Furthermore, targeting Hcy clearance could be a future therapeutic target for DR.

Disclosure
A.M. Tawfik: None. R. Mohamed: None. S. Alhusban: None. S.M. Chu: None. A.Q. Khalil: None. M. Bartolli: None. M. Al-Shabrawey: None.

Funding
American Heart Association (16SDG30700016)
595-P: Progression of Retinopathy in Adolescents with Type 1 Diabetes
Authors: VELAYUTHAM VALLIMAYIL , LIEW GERALD , JANUSZEWSKI ANDRZEJ S. , CHO YOON HI , BENITEZ-AGUIRRE PAUL Z. , CRAIG MARIA E. , JENKINS ALICIA , DONAGHUE KIM C. 
Published: June 2019

Aim: Current guidelines recommend screening for retinopathy from 11 years in youth with type 1 diabetes (T1D) and 2-5 years T1D duration. We examined the longitudinal progression and regression of retinopathy in adolescents seen at our Diabetes Complications assessment service (DCAS) clinic.
Methods: We analyzed digitized retinal photographs taken from 2000-2018 (n=814) in youth with &gt;3 assessments. Retinopathy was graded using the modified Airlie house classification. Generalized estimating equations were used to explore the association between progression/regression and covariates (HbA1c, gender, and diabetes duration).
Results: Mean age at baseline was 13.3+2.6 years, mean T1D duration 6.1+&gt;3.4 years and mean follow- up 7.4 years. Retinopathy was present in 18.7% (n=152) at baseline assessment; with progression in 32.6% (n=266), regression in 7% (n=57) and persistence in 60.3% (n=491). Of those with progression, 185/266 (22.7%) had one step and 81 (9.9%) had &gt; 2 step progression. Factors associated with retinopathy progression were HbA1c and T1D duration and for regression T1D duration (Table 1). Neither height nor SBP was significant for other outcomes.
Conclusion: In adolescents with T1D, retinopathy persistence or progression was greater than of regression. Follow-up of into adulthood will inform the development of appropriate retinopathy screening schedules.

Disclosure
V. Velayutham: None. G. Liew: None. A.S. Januszewski: None. Y. Cho: None. P.Z. Benitez-Aguirre: None. M.E. Craig: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. K.C. Donaghue: None.
599-P: Diabetic Retinopathy (DR) Screening Performance of General Ophthalmologists, Retina Specialists, and Artificial Intelligence (AI): Analysis from a Pivotal Multicenter Prospective Clinical Trial
Authors: IPP ELI , SHAH VIRAL N. , BODE BRUCE W. , SADDA SRINIVAS R. 
Published: June 2019

A prospective study (NCT03112005) evaluated DR screening using the EyeArt AI eye screening system and dilated ophthalmoscopy by board-certified ophthalmologists against the ETDRS clinical reference standard (CRS) of adjudicated expert grading of 4-wide field stereoscopic fundus photographs. A total of 497 subjects with diabetes from 10 U.S. clinical centers underwent undilated 2-field fundus photography for analysis by the EyeArt system, dilated ophthalmoscopy, and dilated 4-wide field stereo fundus photography for the CRS. Performance (Table) of dilated ophthalmoscopy against CRS for identifying referable DR [moderate non-proliferative or higher on the International Clinical Diabetic Retinopathy severity scale or clinically significant macular edema] indicates significant variability across retina specialists and general ophthalmologists. In a previous study, this AI system has been shown to achieve sensitivity 89.0% [95% CI: 87.7-90.2%] and specificity 91.6% [95% CI: 91.0-92.2%] against 7-field ETDRS reference standard. We await the results of the EyeArt system in this multicenter study to verify its ability to provide a more consistent performance for detection of referable DR to facilitate DR screening in primary care and endocrinology clinics.

Disclosure
E. Ipp: Research Support; Self; Eyenuk Inc., Novartis Pharmaceuticals Corporation. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. S.R. Sadda: Consultant; Self; Carl Zeiss Meditec, Centervue, Heidelberg Engineering, Optos. Other Relationship; Self; Nidek. Other Relationship; Spouse/Partner; Topcon.

Funding
Eyenuk Inc.
603-P: Circulating Inflammatory Cells and Inflammasome Activation in Diabetics with Diabetic Retinopathy (DR)
Authors: DUPONT MARIANA D. , LONGHINI ANA LEDA , SREEJIT GOPALKRISHNA , PRASAD RAM , NAGAREDDY PRABHAKARA , GRANT MARIA B. 
Published: June 2019

Increasing evidence points to inflammation as a key component in diabetes-associated retinal perturbations, however, the underlying molecular mechanisms are not yet fully understood. The aims of this study were to characterize peripheral blood mononuclear cells (PBMC) in diabetics with and without DR and to elucidate the biologic role of NLRP3 inflammasome in these cells. PBMC from 33 diabetics (T1D n=9 and T2D n=24) and 18 controls were assessed by flow cytometry. To examine the inflammasome activation, monocytes and neutrophils were treated with the TLR-2 agonist, peptidoglycan (PGN) (10µg/ml) for 3 hours followed by stimulation with a potassium ionophore, nigericin. NLRP3, IL-1β, Caspase-1, IL-18 levels were assessed. Neutrophil counts were significantly higher (1.6 folds, p&lt;0.0002) in diabetics with proliferative diabetic retinopathy (PDR)(45.88%) compared with nondiabetics (28.21%). Increased classical monocytes (88.66%, p&lt;0.0580) were observed in subjects with DR compared to controls (77.66%). Diabetics demonstrated decreased lymphocytes (43.36%, p&lt;0.0007) compared with nondiabetics (58.77%). Lymphocytes were most reduced in T2D with PDR (38.88%) compared to non-DR subjects (43.21%). Expression analysis of inflammasome genes in response to PGN treatment showed a significant increase in monocytes and neutrophil IL-β mRNA expression in diabetic and controls, but no difference whether DR was present or not. Neutrophil IL-β was increased in diabetics at baseline compared to controls. This study demonstrates that increased neutrophils and classical monocytes and reduced lymphocytes are associated with DR. In vitro inflammasome activation studies could not distinguish differences in the level of activation between neutrophils and monocytes obtained from complication-free diabetics and diabetic with DR suggesting the need for repeated measurements of their activation status if these parameters are being used as biomarkers of DR progression.

Disclosure
M.D. DuPont: None. A. Longhini: None. G. Sreejit: None. R. Prasad: None. P. Nagareddy: None. M.B. Grant: None.

Funding
National Institutes of Health (EY028037)
606-P: Point-of-Care Retinal Photography Is Effective in Identifying Diabetic Retinopathy in Patients Not Routinely Followed by Ophthalmology in the Intermountain West
Authors: WAHL MATTHEW , HAYNES ANN , LITCHMAN MICHELLE L. , FAGERLIN ANGELA , DELANEY REBECCA K. , NEUBERGER JULIE , ADJEI-POKU GLADYS S. , SERRATO MARISOL , HARTNETT MARY ELIZABETH , FISHER SIMON 
Published: June 2019

Early detection and treatment of diabetic retinopathy (DR) can reduce blindness risk by &gt;90%. Due to limitations in access to specialized eye care, the majority of people with diabetes (PWD) are not screened routinely. This project aims to determine if implementation of a point-of-care retinal screening program for PWD not routinely followed by ophthalmology would be effective in detecting DR in the Intermountain West region of the U.S. PWD who had not had a dilated eye exam within the last year underwent fundus photography during a regularly scheduled diabetes visit at the University of Utah Diabetes and Endocrinology Center. Non-mydriatic retinal images were classified by a vitreoretinal specialist as to DR severity based on the International Clinical Diabetic Retinopathy and Macular Edema Severity Scale. Abnormal findings were present in 49% of 116 patients imaged: Mild-moderate non-proliferative diabetic retinopathy (NPDR) in 16%, moderate-severe NPDR in 13%, proliferative retinopathy in 4% and hypertensive retinopathy in 13%. Point-of-care retinal imaging effectively identified DR and other retinal conditions in the Intermountain West. The finding of serious eye conditions in PWD not routinely followed by ophthalmologists supports the importance of improving ease of access for eye screening in diabetes care.

Disclosure
M. Wahl: None. A. Haynes: None. M.L. Litchman: None. A. Fagerlin: None. R.K. Delaney: None. J. Neuberger: None. G.S. Adjei-Poku: None. M. Serrato: None. M. Hartnett: None. S. Fisher: None.
614-P: Optimal Control of Glucose and Lipid Profiles Is Critical to the Effective “Neo-Islet” Therapy of Insulin Dependent Pet Dogs
Authors: GOOCH ANNA , CHOWDHURY SABIHA S. , WESTENFELDER CHRISTOF 
Published: June 2019

We demonstrated that ip administration of “Neo-Islets” (NIs; co-aggregation of allogeneic, culture-expanded Islet cells (ICs) with Adipose derived Stem Cells (ASCs)), resulted in their omental engraftment in immune-competent, diabetic NOD mice. This achieved durable euglyciemia without immunosuppression, and with physiologic delivery of insulin and other islet hormones (SCTM 2017;6:1631). We are conducting an FDA guided pilot study (INAD 012-1248) of this technology in spontaneously T1DM pet dogs (see abstract this session). ICs and ASCs are known to be subject to gluco- and lipotoxicity. We undertook this study to determine whether the Hypertriglyceridemic (HTG) and/or DM milieu has an adverse effect (lipotoxic and/or glucotoxic) on dog ASCs and ICs and NIs.
Accordingly, serum was collected from HTG, DM dogs enrolled in INAD 012-776 before and after control of HTG and glucose levels, and from non-DM HTG dogs. These sera were added separately (10%) to DMEM at either 5mM or 17mM glucose for dog ASC and IC cultures. Growth rates and gene expression profiles were assessed.
Serum from DM (glucose 123-742 mg/dL) dogs with untreated HTG (range 656-1248 mg/dL; normal 20-248 mg/dL) killed ICs at either 5 or 17 mM glucose, and failed to support the expansion of ASCs in 17mM glucose. For ASCs grown in 17mM glucose expression of IL-6 and IGF-1 were downregulated. In contrast, sera from DM dogs with controlled HTG (range 146-656 mg/dL), and serum from HTG (range 742-1114 mg/dL), non-DM dogs supported the growth of both cell types in either medium with no changes in gene expression. In agreement with these in vitro results, an uncontrolled NI-treated study dog failed to respond to therapy, while HTG and glucose-controlled dogs have shown up to 50% reduced need for insulin 12 months post therapy.
Conclusion: These data demonstrate the need for optimal glucose and lipid control to prevent destruction of the NI cells when treating DM.

Disclosure
A. Gooch: Board Member; Self; SymbioCellTech. S.S. Chowdhury: Employee; Self; SymbioCellTech. C. Westenfelder: Consultant; Self; SymbioCellTech.
615-P: A Novel Lipid-Lowering Drug Pemafibrate Enhances Effects of Statins in Serum Lipids in Japanese Patients with Type 2 Diabetes
Authors: KUSUNOKI MASATAKA , NATSUME YUKIE , OSHIDA YOSHIHARU , MIYATA TETSURO 
Published: June 2019

Many patients with type 2 diabetes mellitus have dyslipidemia, often both hypercholesterolemia and hypertriglyceridemia. Conventionally, statins in combination with fibrates have been relatively contraindicated in patients with abnormal renal function and are carefully administered in those with normal renal function. In this study, pemafibrate (PFB), a new fibrate, was additionally administered to type 2 diabetic patients with both hypercholesterolemia and hypertriglyceridemia who were already receiving statins, to evaluate the efficacy and safety of the coadministration.
Fourteen patients receiving pitavastatin (1, 2, or 4 mg/day) or rosuvastatin (2.5 or 5 mg/day) for 6 months were additionally administered PFB (0.1 mg, twice daily) for 1 month. Eleven patients receiving lipid-lowering drugs other than statins also additionally received PFB for 1 month. Blood samples were collected before and after the administration of PFB to measure the serum levels of biochemical parameters.
In patients who received PFB in addition to statins, significant improvement was seen in the following lipid parameters: total cholesterol (195 ± 44 deceasing to 177 ± 37 mg/dL, P &lt; 0.05), HDL cholesterol (54 ± 16 to 58 ± 16 mg/dL, P &lt; 0.05), the LDL cholesterol/HDL cholesterol ratio (2.08 ± 0.45 to 1.76 ± 0.57, P&lt;0.05), and triglyceride (246 ± 150 to 137 ± 47 mg/dL, P &lt; 0.05). The drug did not affect hepatic function. In patients who received PFB in addition to lipid-lowering drugs other than statins, only significant decrease of the serum triglyceride was noted. Additional administration of PFB had no effect on body weight, BMI or serum creatinine kinase (CK).
PFB administered with statins yielded a marked improvement of blood lipid profile than PFB administered with lipid-lowering drugs other than statins. No effects were noted on the hepatic function parameters or serum CK. The results suggest the efficacy and safety of PFB in combination with statins.

Disclosure
M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Natsume: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Oshida: None. T. Miyata: Research Support; Self; Bayer AG, Daiichi Sankyo Company, Limited.
62-LB: Quantifying Insulin-Mediated and Noninsulin Mediated Glucose Disposal during Exercise in Patients with Type 1 Diabetes
Authors: NGUYEN THANH-TIN P. , JACOBS PETER G. , CASTLE JESSICA R. , WILSON LEAH M. , BRANIGAN DEBORAH , GABO VIRGINIA , SENF BRIAN , GUILLOT FLORIAN H. , YOUSSEF JOSEPH EL 
Published: June 2019

Introduction: Glycemic control during exercise is challenging for people with type 1 diabetes. Better quantification of insulin dynamics at different exercise intensities and across insulin loading conditions is necessary for accurate insulin dosing during exercise.
Methods: Twenty seven participants with type 1 diabetes were evaluated during 3 separate 10-hour fasting aerobic exercise studies with low, medium, and high levels of insulin infusion (100%, 150%, and 300% of basal rate) across two exercise arms: moderate (40-45% of VO2 max), and intense (60-65% of VO2 max) exercise. Glucose levels were clamped during a 3-hour run-in period, followed by 45 minutes of exercise on a treadmill. 6,6-2H2-dideuterated glucose was infused to match endogenous glucose production during the entire trial. Glucose tracer data were fitted to a two-compartment ODE model, solved via Bayesian inference. We intend to quantify insulin and non-insulin mediated disposal of glucose by observing the rate of disposal (Rd) across different rates of insulin infusion in each exercise arm.
Results: Area under the curve (AUC) of Rd during 45 minutes of moderate exercise increased by 0.084 mmol/L for every percent increase in baseline insulin infusion rate (95% CI=0.064-0.104, p&lt;0.001). AUC during intense exercise increased by 0.109 mmol/L (95% CI= 0.079-0.139, p&lt;0.001). Mixed-effects model analysis showed no difference between exercise arms.
Conclusion: Results indicate Rd is substantial during exercise but that the difference in glucose uptake during aerobic exercise at 40-45% VO2 max may be comparable with 60-65% VO2 max.

Disclosure
T.P. Nguyen: None. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. L.M. Wilson: None. D. Branigan: None. V. Gabo: None. B. Senf: None. F.H. Guillot: None. J. El Youssef: None.

Funding
National Institutes of Health
623-P: Impaired Nrf2 Function Corresponds with Delayed Wound Healing in Diabetes
Authors: KUHN JOSEPH , DAVID JOSHUA A. , VILLARREAL PONCE ALVARO P. , ABDOU SALMA , SULTAN DARREN , KWONG JENNIFER , RABBANI PIUL S. , CERADINI DANIEL 
Published: June 2019

Imbalance in the production of reactive oxygen species predisposes diabetic patients to delayed wound healing, but treatments that directly address this imbalance are lacking. Nrf2 and its natural inhibitor, Keap1, maintain redox homeostasis. However, the exact contribution Nrf2 makes to healing is unclear. Here we demonstrate that Nrf2 loss of function in discreet layers of the epidermis corresponds with substantial oxidative stress burdens and a concomitant delay in healing human tissue. Compared to nondiabetic human epidermal keratinocytes (NHEKs), diabetic human epidermal keratinocytes (DHEKs) exhibit a pro-inflammatory cytokine profile and decreased transcription of downstream antioxidant genes. Silencing Keap1 in DHEKs led to restoration of a cytokine profile conducive to healing (5-fold increase in TGF-b, p=0.0251, and 2-fold reduction in TNFa, p=0.019), a recovery in the expression of antioxidant genes, normalization of oxidative stress loads, and improvement in keratinocyte proliferation compared to siNS-DHEKs. Keap-1 silenced DHEKs recover the ability to migrate in scratch assays with significant improvement over siNS-DHEKs as early as 2 hours post-injury (1255 vs. 1560 mm2, p=0.014). In surgical specimens of wounded nondiabetic skin, Keap1 levels decrease, intranuclear Nrf2 increases, resulting in increased antioxidant gene expression to maintain redox homeostasis. However, in the wounds of diabetic patients, Keap1 remains elevated with a corresponding decrease in active Nrf2. In particular, the basal epidermis of wounded diabetic skin demonstrates a 77% decrease (p=&lt;0.0001) in the expression of Nrf2. We present evidence that human diabetic epidermal Nrf2 dysfunction likely coincides with that of wounded tissue and results in reduced antioxidant gene expression, a rise in reactive oxygen species, and impaired re-epithelization. Exploiting the Nrf2 pathway may show great potential as a therapeutic strategy to minimize pathologic wound burden in the diabetic population.

Disclosure
J. Kuhn: None. J.A. David: None. A.P. Villarreal Ponce: None. S. Abdou: None. D. Sultan: None. J. Kwong: None. P.S. Rabbani: None. D. Ceradini: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-16-ACE-08 to D.C.)