bluuebunny/crossref_metadata_2025_split huggingface dataset:
568-P: ATF4 Regulates the Inflammatory Responses via the Modulation of NLRP3 Inflammasome in Diabetic Retinopathy
Authors: LI TING , HE XUEMIN , PENG RONGDONG , GAO RONG , SHI GUOJUN , CHEN YANMING 
Published: June 2020

Aims: Previously we reported that ATF4-mediated endoplasmic reticulum (ER) stress led to endothelial inflammation and retinal vascular leakage under diabetic condition. In this study, we aimed to investigate if ATF4 regulated the inflammatory responses through modulating NLRP3 inflammasome activation in diabetic retinopathy.
Methods: Streptozotocin (STZ) was applied to induced diabetes in mice. Mice were sacrificed at day 15 and day 30 after onset of diabetes, and retinas were collected for analyses. To mimic the diabetic condition in vitro, human retinal microvascular endothelial cells (HRMECs) were exposed to palmitate (50 μM), accompanied with adenoviruses overexpressing human ATF4 or shRNA of ATF4.
Results: ATF4 level was closely correlated with the activation of NLRP3 inflammasome in STZ-diabetic retinas and palmitate-treated HRMECs, followed by increases of inflammatory factors (ICAM-1, VCAM-1 and TNF-α) and loss of endothelial junction proteins (ZO-1, occludin-1 and VE-cadherin). Moreover, diabetes-induced ATF4 and NRLP3 were colocalized in the ganglion cell layer, inner plexiform layer and outer plexiform layer. Overexpression of ATF4 augmented the palmitate-elicited activation of NLRP3 inflammasome, whereas knocking-down of ATF4 abolished the activation. By analyzing the promoter region of NLRP3 gene, three potential binding sites of ATF4 were identified: -1418bp∼-1406bp, -1332bp∼-1320bp, -65∼-53bp. Overexpression of ATF4 potentiated the palmitate-induced nuclear translocation of ATF4, followed by enhanced activation of NLRP3 inflammasome. In addition, treatment with ISRIB, an inhibitor of ER stress, significantly abolished the palmitate-induced elF2α phosphorylation but not NLRP3 activation when ATF4 is overexpressed.
Conclusion: We have demonstrated that ATF4 is a directly regulator of NLRP3 inflammasome, independent of ER stress response, thus providing a novel insight into the pathogenesis of ATF4-elicited diabetic retinopathy.

Disclosure
T. Li: None. X. He: None. R. Peng: None. R. Gao: None. G. Shi: None. Y. Chen: None.

Funding
Research and Development Plans in Key Areas of Guangdong Province (2019B020227003); National Natural Science Foundation of China (81770826); National Key Research and Development Program of China (2017YFA0105803)
606-P: Artificial Neuronal Network Model for Three-Month Prognosis in Diabetic Foot Syndrome
Authors: PORADZKA ANNA A. , CZUPRYNIAK LESZEK 
Published: June 2020

Background: To make a reliable prognosis on wound healing in patients with diabetic foot syndrome (DFS) is extremely difficult. We used the artificial neuronal network (ANN) to identify the most significant variables which affect DFS healing process. We also aimed at providing data for designing a digital application which would help practitioners to predict the course of DFS.
Methods: We enrolled 213 DFS patients and examined them using a variety of diagnostic tests. The patients were followed for three months. In the initial model, we assessed 35 clinical and biochemical variables. Subsequently, with the help of traditional statistics we reduced their number to twelve, and after conducting the sensitivity analysis, we found out that the final number of significant variables is as low as six.
Results: The most significant variables in predicting the outcome of DFS treatment were: probe-to-bone test result, presence of blood flow in Doppler probe, prior amputation within the foot, erythrocyte sedimentation rate, and the area and duration of the ulceration. The area under the ROC curve was 0.87 (Figure). The total accuracy was 85%, sensitivity 94.6%, specificity 66% and F1 score 89%.
Conclusions: ANN can be used in the prediction of the DFS course. The algorithm, which is the source of a digital application, is particularly useful in identifying individuals with diabetic foot ulcerations who fail to be healed in three months.

Disclosure
A.A. Poradzka: Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Urgo Medical. L. Czupryniak: None.
612-P: Randomized Controlled Prospective Study of the Effects of Structured Outpatient Diabetes Program on the Hospital Readmission Rates (RR) in Patients with Diabetes (DM)
Authors: BHALODKAR ARPITA , SONMEZ HALIS , LESSER MARTIN , LEUNG TUNG MING , ZISKOVICH KARINA , INLALL DAMIAN , PORETSKY LEONID , KRYMSKAYA MARINA , MURRAY-BACHMANN RENEE 
Published: June 2020

Introduction: DM is associated with a higher risk of readmissions. We examined the effects of a structured diabetes outpatient program on RR.
Methods: Patients hospitalized with a primary or secondary diagnosis of DM were randomized to standard care (control group [C]) or a structured diabetes program (intervention group [I]) upon discharge. The structured program included a visit to the CDE nurse practitioner (NP) who developed individualized plan for every subject. Subsequent visits were with an NP, nutritionist, social worker and endocrinologist as needed. RR data were generated from electronic medical records and included emergency department (ED) as well as hospital admissions. RR were calculated by dividing the number of readmissions by the number of initial (index) admissions and expressed as %.
Results: 192 subjects were recruited (95 into [C] and 97 into [I]). The mean age was 56±13 yrs [C] and 60±12 yrs [I]. The [C] had 56 (29%) males and 39 (20%) females; [I] had 60 (31%) males and 37 (19%) females. 66 (35%) subjects were African American, 2 (1%) American Indian, 1 (0.5%) Hawaiian, 57 (30%) Caucasian, 11 (5%) Asian, 12 (6%) identified as more than one race, 43 (22%) of unknown race. There were no statistically significant differences between the groups in these characteristics. The 30-day RR: overall (ED and Hospital): 19% [C] and 7% [I], p=0.01; Hospital: 9% [C] and 4% [I], p=0.14; ED: 17% [C] and 4% [I], p=0.003. The 365-day RR: overall 38% [C] and 14% [I], p=0.0002; Hospital: 33% [C] and 8% [I], p&lt;0.001; ED: 34% [C] and 11% [I], p=0.0002.
Conclusion: A structured outpatient diabetes program reduced RR in DM patients when compared with standard care. 30 day RR were reduced primarily due to a reduction in the ED visits, whereas 365 day RR were reduced due the reduction in both ED visits and hospital admissions. Larger multicenter studies are needed to confirm these data.

Disclosure
A. Bhalodkar: None. H. Sonmez: None. M. Lesser: None. T. Leung: None. K. Ziskovich: None. D. Inlall: None. L. Poretsky: None. M. Krymskaya: None. R. Murray-Bachmann: None.
630-P: Targeting Workload Experienced by Diabetes Camp Medical Staff: A Novel Training Curriculum
Authors: ATWOOD ERIN S. , SHEANON NICOLE M. , AMANAT SHEILA , KHOURY JANE C. , KLEIN MELISSA 
Published: June 2020

More than 5700 children with diabetes attend American Diabetes Association (ADA) camps each year. Training volunteer medical staff has become more challenging given the rapid advances in diabetes technology. Through a prospective, multi-site pilot study at 4 ADA camps, we assessed the efficacy of an educational bundle of online interactive cases with in-situ simulation in preparing medical volunteers for management of type 1 diabetes (T1D). We hypothesized that our curriculum would reduce the workload necessary to manage children with T1D as measured by the NASA-Task load index (TLX), a validated workload assessment tool comprised of 6 self-rated scales; mental, physical, and temporal demand, performance, effort, and frustration. No statistical difference in change in workload was observed between the intervention and control groups (Table 1). However, both groups were small and had different experiences prior to camp. The reduction in temporal demand reported by the intervention group by the end of camp may signal an impact among medical providers. Future interventions, with larger, more balanced groups, could evaluate timing of TLX change and the effect on medical staff’s camp experience and patient care.

Disclosure
E.S. Atwood: Research Support; Self; American Diabetes Association. N.M. Sheanon: Research Support; Self; American Diabetes Association. S. Amanat: None. J.C. Khoury: None. M. Klein: None.
648-P: Do Social Determinants of Health (SDoH) Influence Participant Outcomes of Those Enrolled in the Diabetes Prevention Program, Montana 2015-2018?
Authors: CARPENEDO DOROTA , TYSK SONJA , HOUSE MELISSA , FERNANDES JESSIE , BUTCHER MARCI K. , HARWELL TODD S. , HELGERSON STEVEN D. , GOHDES DOROTHY M. 
Published: June 2020

Research on health disparities among participants in the Diabetes Prevention Program (DPP) is limited. This study examined the outcomes of the DPP participants in Montana based on their Social Determinants of Health (SDoH) risk score. Participants in Montana’s DPP were assigned 1 point for each of the SDoH variables; ≤ High School, unemployment, annual household income below Federal Poverty Level, no health insurance, or lived in rural area. From 2015 through 2018, 2,900 MT adults enrolled in the DPP; 39% had a total SDoH risk score of ≥1 (Table). All risk groups lost weight, although logistic regression models found that as the SDoH risk score increased, the odds of achieving 5% weight loss decreased [AOR 1.61, 95% 1.24-2.09], compared to enrollees who scored 0. Characteristics independently associated with not meeting the 5% weight loss included age 18-44 years [AOR 1.58, 95% 1.26-1.99], BMI (kg/m2) 35+ [AOR 1.38, 95% 1.12-1.69], and female [AOR 1.31, 95% 1.08-1.60]. To effectively address health disparities and assist participants in meeting the 5% weight loss, the DPP lifestyle coaches (LSCs) and health care providers can use the SDoH risk score to identify participants who can benefit from accessing community-based programs. Additionally, LSCs can eliminate barriers by offering childcare, transportation or other incentives to better participation.

Disclosure
D. Carpenedo: None. S. Tysk: None. M. House: None. J. Fernandes: None. M.K. Butcher: None. T.S. Harwell: None. S.D. Helgerson: None. D.M. Gohdes: None.
655-P: Improved Outcomes with Diabetes Devices Using Lower-Literacy Teaching Guides in a Center for Underserved Individuals with Type 1 Diabetes
Authors: PETERS ANNE L. , WALKER MARTHA A. , RUELAS VALERIE F. 
Published: June 2020

Healthcare disparities exist between those in more or less affluent communities. This is particularly true for diabetes devices, where intensive training and follow-up is needed. Materials are generally written at an 11th grade reading level. Further, illustrations generally show low ethnic diversity. To reduce this educational gap, we created lower literacy, English and Spanish, multicultural guides for insulin pen and pump use. Focus groups provided input, nonbranded illustrations were created, and the text was edited by the “Clear Language Group.”
Methods: The guides were implemented in our clinic for underserved, largely Hispanic, individuals in East Los Angeles. 47 adults with T1D were included. Subjects were given the low literacy guides and participated in guide driven individual and group education. Measures administered at baseline and 12 months were assessed for normality and independent sample t-tests. A 2-sided alpha of 0.05 was used.
Results: Initial A1C was 9.2 +/- 1.97 (SD) with no change over the study course (12-month A1C = 9.3 +/- 1.92). However, patients showed an improved overall self-report of health (p = 0.012), improvement in diabetes knowledge (Michigan Diabetes Knowledge Test, p=.004), a reduction in symptoms of depression (PHQ8, p=.042), and diabetes distress (Diabetes Distress Scale, T1D Redeem, p = 0.0123). Though no change in rates of hypoglycemia, a reduction in fear of hypoglycemia (Hypoglycemia Fear Scale, Fear sub-scale, P=0.025) was significant. Additionally, there was a reduction in rates of DKA (0.0108). Time in range was minimal, based on blinded CGM, at baseline (22.4%) and did not change at 12 months (24.0%). CGM data was only available on 25 patients due to patient reluctance to wear the device.
Conclusions: Appropriately targeted teaching guides can be used to improve a variety of outcomes in people with T1D, including rates of DKA. However, more work is needed to make a significant impact on glycemic control.

Disclosure
A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. M.A. Walker: None. V.F. Ruelas: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
659-P: Effect of Coaching en Diabetes (CoeD) Program on Glycemic Control in Steel Workers with Type 2 Diabetes
Authors: ROMERO-IBARGUENGOITIA MARIA ELENA , CANTU SANTOS OSCAR M. , GONZALEZ DALIA GUTIERREZ , FACIO ROSALINDA GONZALEZ , GONZALEZ-CANTU ARNULFO 
Published: June 2020

Patients with type 2 diabetes (T2D) could improve its glucose control with a multidisciplinary cultural management. Coaching en Diabetes (CoeD) is a multicomponent program for steel workers and their direct families with T2D when their A1C is &gt;9% as an effort to increase attachment to medical treatment. The program focusses on the empowerment and glucose treatment sensibilization through a group medical visit, improvement of self-management and medical treatment. CoeD is performed by a multidisciplinary team (internist, nutritionist, diabetes educator, social worker, etc.). The aim of this study is to evaluate the effect of this program in glycemic control through 2 years of follow-up. This is a retrospective and longitudinal study of patients with uncontrolled T2D at Clinica Nova from Monterrey, Mexico. This study was conducted from May 2017 to 2019. We used descriptive statistics and ANOVA of repeated measures when it was appropriate. We included a total of 153 [115 (75.2%) males], with a mean (SD) age of 62.9 (11.2) years. The duration of T2D was 9.7 (6.6) years. During the follow-up 26 patients (17%) left the program, 2 of them died in relation to cardiovascular disease. All patients maintained a controlled blood pressure. We found a reduction of A1C of 1.5% [Mean (SD) 9.8% (1.5) to 8.3% (1.6), p=0.032) and fasting glucose of 41.8 mg/dl [Mean (SD) 180mg/dl (67) to 138.2mg/dl (55), p=0.021). These reductions were maintained through the 24 months of follow-up. The CoeD program was successful in reducing and sustaining A1C and pre-prandial glucose reduction in this group of patients.

Disclosure
M. Romero-Ibarguengoitia: None. O.M. Cantu Santos: None. D. Gutierrez Gonzalez: None. R. Gonzalez Facio: None. A. Gonzalez-Cantu: None.
66-LB: Combined Immunotherapy with T Regulatory Cells and Anti-CD20 Antibody Prolongs Survival of Pancreatic Islets in Type 1 Diabetes
Authors: ZIELINSKI MACIEJ , ZALINSKA MAGDALENA , IWASZKIEWICZ-GRZES DOROTA , GLIWINSKI MATEUSZ , HENNIG MATYLDA , JAZWINSKA-CURYLLO ANNA , KAMINSKA HALLA , SAKOWSKA JUSTYNA , OWCZUK RADOSLAW , MLYNARSKI WOJCIECH , JAROSZ-CHOBOT PRZEMYSLAWA , BOSSOWSKI ARTUR , SZADKOWSKA AGNIESZKA , SIEBERT JANUSZ , MYSLIWIEC MALGORZATA , MAREK-TRZONKOWSKA NATALIA M. , TRZONKOWSKI PIOTR 
Published: June 2020

Background: Immunotherapy using T regulatory cells (Tregs, Tr) prolongs remission in type 1 diabetes (T1DM) but the effect fades with the time. Here, we report phase II trial in which Tregs therapy was combined with anti-CD20 antibody (TrCD20) to make the effect more sustained.
Methods: Thirty-six children with newly diagnosed T1DM were randomized 1:1:1 into the following groups: Tr, TrCD20 and control. The treatment in Tr group consisted of autologous expanded CD3+CD4+CD25highCD127- Tregs in the two doses (30x106 of Tregs/kg b.w. each), three months apart. TrCD20 group received additionally 4 doses of rituximab (375 mg/m2, each) between the first and second dose of Tregs. Control group was left without the treatment and all patients were followed for 2 years.
Results: The best results were found in TrCD20 group, who was characterized by stable serum levels of both fasting C-peptide and stimulated C-peptide in glucagon and MMT tests throughout the entire trial (for fasting C-peptide only 20% decrease at +24months when compared to baseline). Tr group was characterized by stable levels of fasting and stimulated C-peptide up to +12months and then it dropped gradually until the end of the trial. As compared to control group, there was a better glycemic control measured as HbA1c and mean fasting glucose in both interventional groups throughout the whole follow up. TrCD20 group was in partial remission defined as insulin dose below 0.5IU/kg up to +21 months. The longest insulin independent follow up lasted 18months. The end of the remission in Tr group was noted at +18month and in controls at +12months. At the +24months daily insulin requirement and HbA1c levels were significantly lower in TrCD20 as compared to control group.
Conclusions: The combined immunotherapy with Tregs and anti-CD20 antibody prolonged the most significantly survival of pancreatic islets in T1DM children. Trial registration: EudraCT: 2014-004319-35.

Disclosure
M. Zielinski: None. M. Zalinska: None. D. Iwaszkiewicz-Grzes: None. M. Gliwinski: None. M. Hennig: None. A. Jazwinska-Curyllo: None. H. Kaminska: None. J. Sakowska: Employee; Self; Poltreg S.A. R. Owczuk: None. W. Mlynarski: None. P. Jarosz-Chobot: None. A. Bossowski: None. A. Szadkowska: None. J. Siebert: None. M. Mysliwiec: Stock/Shareholder; Self; POLTREG SA. N.M. Marek-Trzonkowska: Stock/Shareholder; Self; Poltreg SA. P. Trzonkowski: Board Member; Self; Poltreg S.A. Stock/Shareholder; Self; Poltreg S.A.

Funding
National Centre for Research and Development in Poland (STRATEGMED1/233368/1/NCBR/2014)
680-P: Residual ß-Cell Function in Long-Term Type 1 Diabetes Is Associated with a Fivefold Greater Mobilization of Endothelial Progenitor Cells after Exercise
Authors: TAYLOR GUY S. , SMITH KIERAN , SCRAGG JADINE , BASHIR AYAT , FLATT ANNELIESE , STEVENSON EMMA J. , MCDONALD TIMOTHY J. , ORAM RICHARD A. , SHAW JAMES A. , ROSS MARK D. , WEST DANIEL J. 
Published: June 2020

Aims: β-cells can function for years after diagnosis in people with type 1 diabetes (T1D). It is unknown how C-peptide secretion impacts upon rare blood vessel protecting Endothelial and Hematopoietic Progenitor Cells (EPCs and HPCs), particularly in response to cardiovascular stress, such as exercise. We compared EPC and HPC counts at rest and after acute exercise in clinically diagnosed people with T1D with undetectable and high C-peptide.
Methods: After quantification of stimulated C-peptide, 11 participants with undetectable C-peptide (Cpepund &lt;3 pmol/L) and 10 with high C-peptide (Cpephigh &gt;200 pmol/L) were recruited, with no differences in age, fitness or HbA1c, while the Cpephigh group had shorter diabetes duration (27±13 vs. 11±3 years, p=0.01). After a maximal exercise test, participants attended a third visit to complete 45mins of walking at 60%VO2peak. Blood samples were taken at rest, immediately and 1 hour post exercise. Two HPC and five EPC phenotypes were enumerated by flow cytometry. Data (mean±SD) were analysed by two-way ANOVA and t-test with significance accepted at p≤0.05.
Results: The Cpephigh group displayed higher rest values of HPCs than the Cpepund group, and increased rest to post exercise mobilization (p&lt;0.05). While resting counts were similar, exercise mobilized all EPC phenotypes in the Cpephigh group with no significant changes in the Cpepund group. CD34+CD45dimVEGFR2+ EPCs did not differ at rest (Cpephigh 28±13 vs. Cpeplow 22±7 cells/ml, p=0.22), while Cpephigh increased from rest to post exercise by 25±22 vs. 5±15 cells/ml in the Cpepund group (p=0.02).
Conclusion: People with T1D who maintained a high residual β-cell function had increased counts of HPCs and EPCs, and sustained a &gt;5 fold exercise mobilization of EPCs compared to people with no C-peptide. Future research needs to understand if these differences are due to clinical characteristics or the potential direct impact of C-peptide upon vasculature.

Disclosure
K. Smith: None. J. Scragg: None. A. Bashir: None. A. Flatt: None. E.J. Stevenson: None. T.J. McDonald: None. R.A. Oram: None. J.A. Shaw: Advisory Panel; Self; Medtronic. Speaker’s Bureau; Self; Novo Nordisk A/S. M.D. Ross: None. D.J. West: None.

Funding
Diabetes Research & Wellness Foundation (to D.J.W.)
695-P: Grand-Maternal Exercise Improves Glucose Tolerance in Second Generation Offspring
Authors: WAGNER ANA B.A. , KUSUYAMA JOJI , NIGRO PASQUALE , MAKAREWICZ NATHAN S. , HIRSHMAN MICHAEL F. , GOODYEAR LAURIE J. 
Published: June 2020

Maternal obesity and diet are critical risk factors for development of obesity and diabetes in both first (F1) and second (F2) generation offspring. Maternal exercise in mice improves F1 metabolic health and prevents the detrimental effects of maternal high-fat-diet (HFD) on F1 offspring. Whether the beneficial effects of maternal exercise can be transmitted to the F2 generation is unknown. Here, C57BL/6 females were fed a chow or HFD and subdivided into cages with (Exercise) or without (Sedentary) running wheels for 2wks before breeding and during ∼3wks gestation. Male F1 offspring were sedentary and chow-fed, and at 8 wks of age were bred with age-matched females from untreated parents. F2 offspring were studied based on grand-maternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained (n= ∼10 litters/group; 348 total mice). F2 offspring were sedentary and chow-fed and studied up to 52 wks of age. For F2 males, grand-maternal exercise significantly improved glucose tolerance at 24, 36 and 52 wks and decreased insulin concentrations at 52 wks. Grand-maternal exercise also resulted in F2 males with lower body weights, decreased fat mass and increased lean mass at 52wks. Grand-maternal HFD decreased glucose uptake in skeletal muscles and adipose tissue in F2 males, but there was no effect of grand-maternal exercise, suggesting that the mechanism for improved glucose tolerance in F2 males does not involve glucose uptake in these tissues. For female F2, grand-maternal exercise had no effect on insulin concentrations, body weights or tissue glucose uptake. However, grand-maternal exercise significantly improved glucose tolerance in female F2 at 36 and 52 wks, and decreased fat mass and increased lean mass. Maternal exercise has beneficial effects on the metabolic health of adult F2 male and female offspring. These novel findings suggest that maternal exercise can prevent obesity and diabetes in multiple generations and may help reduce the incidence of these diseases worldwide.

Disclosure
A.B.A. Wagner: None. J. Kusuyama: None. P. Nigro: None. N.S. Makarewicz: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. L.J. Goodyear: None.

Funding
American Diabetes Association (1-17-PMF-009 to A.B.A.W.); National Institutes of Health (R01DK101043)