bluuebunny/crossref_metadata_2025_split huggingface dataset:
214-OR: Role of Hypothalamic MAPK/ERK Signaling in Diabetes Remission Induced by the Central Action of Fibroblast Growth Factor 1 (FGF1)
Authors: BROWN JENNY M. , PHAN BAO ANH N. , WASANWALA HUZAIFA , MATSEN MILES E. , SECHER ANNA , MORTON GREGORY J. , SCHWARTZ MICHAEL W. , SCARLETT JARRAD 
Published: June 2020

The hypothalamic arcuate nucleus-median eminence (ARC-ME) is a target for sustained diabetes remission induced by fibroblast growth factor 1 (FGF1). To identify intracellular signaling cascades underlying this effect, we considered evidence that sustained signal transduction responses engaged by FGF1 are integrin-dependent. To determine if the sustained antidiabetic response of diabetic ob/ob mice to intracerebroventricular (icv) injection of FGF1 is also integrin-dependent, we investigated the response to a mutant FGF1 that is unable to activate integrin receptors (R50E FGF1). We found that although icv injection of R50E FGF1 mimics the transient anorexia, weight loss and blood glucose lowering responses induced by native FGF1 (P&lt;0.001 vs. Veh for each), it fails to elicit sustained diabetes remission. Similarly, MAPK/ERK signaling is induced in the ARC-ME (primarily in tanycytes) for up to 24 h following a single icv FGF1 injection in both wild type and ob/ob mice, but the duration of this response is reduced by∼70% following icv R50E FGF1 injection (P&lt;0.0001 vs. icv FGF1). We therefore hypothesized that owing to its integrin-dependent nature, FGF1-induced remission of diabetic hyperglycemia requires sustained activation of the MAPK/ERK signaling pathway in the ARC-ME. To test this hypothesis, 4 groups of diabetic ob/ob mice were studied. Each group received a single icv injection of either saline vehicle or recombinant FGF1 (3 µg), followed immediately by continuous icv infusion of either the MAPK inhibitor U0126 or its vehicle (DMSO) for 24 h. We report that the duration of the antidiabetic effect induced by icv FGF1 injection is attenuated by pharmacologic blockade of MAPK/ERK signaling. We conclude that the sustained remission of diabetic hyperglycemia induced by the central action of FGF1 depends upon its ability to activate hypothalamic MAPK/ERK signaling in a sustained manner.

Disclosure
J.M. Brown: None. B.N. Phan: None. H. Wasanwala: None. M.E. Matsen: None. A. Secher: Employee; Spouse/Partner; Gubra. Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. G.J. Morton: Research Support; Self; Novo Nordisk A/S. M.W. Schwartz: Research Support; Self; Novo Nordisk A/S. J. Scarlett: None.

Funding
National Institutes of Health (K08DK114474, DK101997, DK083042, DK035816, P30DK017047, HL007312); University of Washington
2150-PUB: Chemotactic Cytokine Receptor 5 (CCR5) Gene Promoter Polymorphism (rs1799987) Is Associated with the Risk of Diabetic Kidney Disease in Polish Patients with Type 2 Diabetes
Authors: NABRDALIK KATARZYNA , POKRZYWNICKA PATRYCJA S. , KWIENDACZ HANNA , ADAMCZYK PIOTR , MOCZULSKI DARIUSZ , MOCZULSKA HANNA , DROZDZ KAROLINA , GRZESZCZAK WLADYSLAW , GUMPRECHT JANUSZ 
Published: June 2020

Background and Aims: The environmental risk factors of diabetic kidney disease (DKD) do not allow identification of people at higher risk of it. A lot of expectations are being placed to the genetic predisposition. Among patients with diabetes, the presence of CCR5 gene polymorphism is suspected to be associated with DKD, yet the results are inconclusive. The aim of this study was to evaluate its association with DKD among Polish patients with type 2 (T2DM).
Materials and Methods: CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among 467 consecutive patients with T2DM visiting one outpatient diabetology clinic in Upper Silesia, Poland. DKD diagnosis was based on urinary albumin creatinine ratio &gt;300 mg/g and the presence of diabetic retinopathy. Information related to time of diabetes duration and HbA1c were collected.
Results: Clinical characteristic of studied patients is presented in Table 1. We found that both GG genotype (p=0.035) and allele G (p=0.02) were significantly associated with DKD occurrence and G allele was present in all of the DKD patients.
Conclusion: A significant association between rs1799987 polymorphism of CCR5 gene and the presence of DKD in the group of Polish patients with T2DM was found what is in accordance with some previous studies. Further studies are needed in this area to confirm this association.

Disclosure
K. Nabrdalik: None. P.S. Pokrzywnicka: None. H. Kwiendacz: None. P. Adamczyk: None. D. Moczulski: None. H. Moczulska: None. K. Drozdz: None. W. Grzeszczak: None. J. Gumprecht: Consultant; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. Speaker’s Bureau; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier.
2157-PUB: The Effects of an External Shoe-Lift on Off-Loading the Diabetic Foot
Authors: ERSEN ALI , JUPITER DANIEL , RASPOVIC KATHERINE M. , LAVERY LAWRENCE A. , YAVUZ METIN 
Published: June 2020

Diabetic foot ulcers (DFUs) are a complication of diabetes, reducing patients’ quality of life, increasing morbidities, and contributing to more the $30B annually in increased for the U.S. healthcare system. Total Contact Cast (TCC) is considered the gold standard for healing DFUs. Within the last decade a number of prefabricated TCC kits such as TCC-EZ have been introduced, which offer a user-friendly casting process for healthcare providers. However, these casts and their associated boots or shoes cause asymmetry in gait. They may also result in reduction of weight bearing on the casted side and eventually affect the healing of DFUs. The purpose of this exploratory study was to determine the effectiveness of a shoe balancer called Evenup in redistribution of plantar peak pressure (PP) during gait. Sixteen subjects provided informed consent, 5 of whom had diabetic neuropathy (one Type I, four Type II), and completed three trials of 30-m walking while fitted with TCC-EZ and TCC, either with or without Evenup, in a randomized order. A pair of automated wireless photogate sensors captured time to traverse the distance, and pedobarographic insoles (Novel, Germany) measured and recorded plantar pressures. For each trial, the mid-gait six steps for each side were analyzed. Paired t-tests were used to compare bilateral PP difference, as well as whether presence of Evenup changed differences in pressure side to side. Bilateral PP difference in TCC (p=0.166) and TCC-EZ (p=0.123) arms did not reveal significance due to presence of Evenup (p&gt;0.05) while both modalities showed significant PP reduction side to side (p≤0.001). More research is necessary to reveal the potential clinical benefits of the use of shoe lifts in diabetic foot offloading, falls in diabetic patients and healing rates in a larger cohort.

Disclosure
A. Ersen: None. D. Jupiter: None. K.M. Raspovic: Consultant; Self; Orthofix. L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew. M. Yavuz: Research Support; Self; Integra LifeSciences. Other Relationship; Self; Vivonics Inc.

Funding
Integra LifeSciences
218-OR: Does Antibiotic Treatment before Bone Biopsy Affect the Identification of Bacterial Pathogens from Bone Culture?
Authors: LAVERY LAWRENCE A. , RYAN EASTON C. , TRUONG DAVID H. , JOHNSON MATTHEW J. , FONTAINE JAVIER LA , CRISOLOGO PETER A. 
Published: June 2020

Our aim was to evaluate the effect of antibiotic exposure on bacterial pathogen yield in patients with diabetic foot osteomyelitis. In a retrospective cohort study, we evaluated 142 patients admitted to the hospital with diabetic foot osteomyelitis which confirmed by histologic evaluation. Histologic criteria for osteomyelitis included the presence of an inflammatory response, bone necrosis, and/or bone fragmentation. We compared bacterial pathogens in patients that received antibiotics before bone culture (n=114) and patients that did not receive antibiotics (n=28), as well as bacterial yield based on the duration of antibiotic exposure. We used the chi square test to compare antibiotic exposure and culture yield. There was not a significant difference in culture yield in patients that received antibiotics (77.9%) and patients that did not (85.7%, p=0.58). There was no difference in patients that received antibiotics for ≥4 days (n=56, 71.4%), 1-3 days (n=58, 84.5%) and no antibiotics (85.7%, p=0.15).
In conclusion, the results of bacterial recovery were similar in patients regardless of the length of antibiotic treatment. Antibiotic exposure did not change the bacterial yield, the type of bacteria or the number of bacteria. In patients with suspected diabetic foot osteomyelitis, there is no evidence to support withholding antibiotics prior to obtaining a bone biopsy.

Disclosure
L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew. E.C. Ryan: None. D.H. Truong: None. M.J. Johnson: None. J. La Fontaine: None. P.A. Crisologo: None.
2202-PUB: Do Women with Diabetes in Pregnancy Have Better Medication Adherence to Long-Acting Insulin Compared with Intermediate Insulin?
Authors: NAZEER SARAH A. , HERRICK CYNTHIA J. , DUCKHAM HILLARY E. , CARTER EBONY B. 
Published: June 2020

Objective: To determine whether women with pre-existing and gestational diabetes have better medication adherence and pregnancy outcomes when treated with long acting, compared to intermediate acting, insulin.
Methods: We performed a retrospective cohort study of all pregnancies complicated by pregestational and gestational DM from 2007-2017 at a Resident Diabetes in Pregnancy clinic at an academic tertiary care center. Patients were excluded if they did not take long acting or intermediate insulin or took an oral agent in addition, had end stage organ damage, multiple gestation, or fetal anomalies. The primary outcome was maternal medication adherence per physician report. The secondary outcome was a composite neonatal outcome including macrosomia, NICU admission, LGA, shoulder dystocia, individual components of the composite, and glycemic control. Demographic characteristics were compared between groups and logistic regression was used to adjust for potential confounders, including advanced maternal age, weight, race, body mass index, and substance abuse.
Results: Of 926 patients seen during the study period, 808 women met study criteria, by diabetes type: type 1 (n=48), type 2 (n=293) and GDM (n=467). Demographic characteristics were similar between those who used long-acting vs. intermediate insulin. Adjusted analysis using logistic regression demonstrated no significant difference in medication adherence between groups. There was also no difference in the neonatal composite outcome, components of the composite, or glycemic control. Results were similar in stratified analysis by diabetes type.
Conclusion: Medication adherence was similar between women using long and intermediate acting insulin and there was no change in neonatal outcomes. Our findings call into question the notion that the twice daily dosing of intermediate insulin in pregnancy provides tighter glycemic control, although medication adherence did not suffer.

Disclosure
S.A. Nazeer: None. C.J. Herrick: None. H.E. Duckham: None. E.B. Carter: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-19-ACE-02 to E.B.C.)
2225-PUB: Direct Actions of the Dual SGLT1/2 Inhibitor Sotagliflozin on Functional Recovery following Global Ischemia in Diabetic and Healthy Mouse Hearts
Authors: DOREY EMILY S. , COTTER BROOKE , MULLINS THOMAS P. , REICHELT MELISSA E. , GALLO LINDA A. 
Published: June 2020

Sotagliflozin is a dual sodium-dependent glucose transporter (SGLT) inhibitor with the potential to be cardio-protective in people with and without diabetes. Here, we used an ex vivo Langendorff reperfusion model to investigate if direct infusion with sotagliflozin in hearts from diabetic and healthy mice improves functional recovery from global ischemia. Male C57Bl/6 mice were fed either a control chow (CON) or high fat diet (HFD; 60% of calories from fat) for 46-48 weeks. Fasting blood glucose measurements were performed and body composition measured using nuclear magnetic resonance. Constant pressure Langendorff perfusion experiments were performed on hearts from each diet group. Following equilibration, hearts were infused with either sotagliflozin (90 nM) or dimethyl sulfoxide (VEH) for 10 min prior to a 25 min period of global ischemia. The infusions were recommenced for the first 15 min of 45 min reperfusion. Post ischemic recovery was assessed as % baseline recovery. HFD mice were heavier (54 vs. 34 g) with increased fat mass (42 vs. 19 %) and increased fasting blood glucose (9.6 vs. 8.0 mmol/L). Paradoxically, their functional recovery from global ischemia was, in general, better when compared with hearts from CON mice and there was no effect of sotagliflozin infusion. In CON mice, early post-ischemic coronary flow was greater with sotagliflozin infusion when compared with VEH. Functional recovery in dP/dtmax and dP/dtmin was also greater with sotagliflozin infusion when compared with VEH.
In conclusion, HFD exerted a protective effect on heart function, despite inducing obesity and hyperglycemia. Ongoing studies are examining the effects of sotagliflozin in an alternative model of T2DM. In lean mice, sotagliflozin increased functional recovery from global ischemia, highlighting the potential benefits of an antidiabetic agent in acute coronary care.

Disclosure
E.S. Dorey: None. B. Cotter: None. T.P. Mullins: None. M.E. Reichelt: None. L.A. Gallo: None.

Funding
Diabetes Australia
2228-PUB: Utilizing a Diverse Stakeholder Group to Build a Patient-Centered Type 1 Diabetes Research Agenda
Authors: JEWELL VANESSA D. , ABBOTT AMY A. 
Published: June 2020

Engaging patient’s in the research process is essential as it creates self-awareness, increases a collective understanding of needs and views, and allows for active participation in healthcare decisions. This stakeholder driven project aimed to develop a patient-centered research model to identify stakeholders of type 1 diabetes (T1D) for addressing the needs of patients and families in rural communities. From project inception, investigators used an innovative approach of incorporating stakeholders in the entire research process. A four-step engagement plan using the Methods in Community-Based Participatory Research for Health guided the project. In the first strategy, assessment of both personal and institutional capacities for active collaboration was completed. Specifically, the project lead (researcher, healthcare provider, and mother of a child with type 1 diabetes), caregiver, and advocacy organization executive met to discuss strengths and weaknesses and how to effectively collaborate. Next, identification of potential partners ensued with new and established networks, associations, and community leaders. We completed this step through years of networking and becoming involved within the community. Reframing the ultimate health issue for research was the third strategy. This was a dynamic, interactive process guided by a diverse group of stakeholder perspectives across two states in the development of a patient-centered research plan. Finally, developing and nurturing the sustained partnerships established between researchers and community partners was accomplished in strategy four. Specifically, the team developed a group process contract that allowed for fluctuation to meet individual and group needs. These relationships were built through sustained T1D community presence and networking. This shared decision-making process resulted in trust, accountability, and stakeholder empowerment while ensuring that individual’s voices were heard.

Disclosure
V.D. Jewell: None. A.A. Abbott: None.

Funding
Patient-Centered Outcomes Research Institute (10443-CU)
2235-PUB: Improving Rates of Monitoring for Type 2 Diabetes Complications
Authors: SINGH PUJA , WOLFGRAM PETER 
Published: June 2020

Introduction: To compare our diabetes clinic’s baseline adherence to American Diabetes Association (ADA) and International Society of Pediatric and Adolescent (ISPAD) guidelines for obtaining urine creatinine/albumin ratio (ACR), liver enzymes (LFTs) and lipids at diagnosis with type 2 diabetes (T2D) to the rates of screening adherence following institution of educational flowcharts, revised note templates, and a best practice advisory (BPA).
Methods: Data was extracted from Epic including all patients seen initially in our diabetes outpatient clinic with recently diagnosed T2D from 7/2014-8/2019. Data included dates of initial patient visits to our clinic and dates of ACR, LFTs, and lipid order placement or previous lab results. Vizio flowcharts and a revised clinic note template reflecting ADA/ISPAD guidelines were created and presented to the clinic’s 8 attendings and 5 APNPs in 7/2016. In 10/2017, a BPA alert containing the recommended labs began firing if T2D was on the patient’s problem list. A provider was considered adherent to the guidelines if labs were available from the previous 6 months or ordered within 120 days of diagnosis. Pre and post-screening rates were compared using the t-test.
Results: Analysis included 40 patients diagnosed with T2D before any interventions and 39 after the 10/2017 BPA began. The improvement in urine ACR ordering rate was significant as it went from a baseline of 32.5% up to 82.1% (p&lt;0.001), while improvements in the LFT ordering rate (60.0% up to 74.4%; p=0.2) and the lipid order rate (70.0% up to 79.0%; p=0.4) were not significant.
Conclusion: With the implementation of the T2D flowchart, templated note, and BPA, adherence to ADA/ISPAD of ordering baseline screening labs rose to the 70-80% range. Given our aim to detect and treat complication as early as possible, and in order to increase reliability of our care, we are going to begin posting quarterly run charts so both the ordering provider and the diabetes nurses are consistently updated on our adherence rates.

Disclosure
P. Singh: None. P. Wolfgram: None.
2240-PUB: Predictability of HbA1c Control Based on Pharmacotherapy Regimen or the Number of Diabetes-Related Touches in a Rural Population
Authors: VASCIMINI ANGELINA , SULLIVAN TARA , CURTIS STACEY D. , DEREMER CHRISTINA E. 
Published: June 2020

Given the explosion of pharmacologic agents indicated for patients diagnosed with type 2 diabetes, coupled with the decline in physicians practicing in rural settings, pharmacists are positioned to serve as extenders. In this resource-limited environment, assumptions are often applied to predict outcomes based on patient’s frequency of appointments or pharmacotherapy regimen. The goal of this study is to determine if select medications or the number of clinical touches support assumptions predicting a patient’s HbA1c control.
A single center retrospective chart review was conducted for patients with an ICD-10 code related to type 2 diabetes. Data extracted from the electronic medical record included demographics, HbA1c with trend, dates of diagnosis, pharmacotherapy regimen, and number of clinical diabetes related touches. Touches were defined as documentation of diabetes related management through office appointment or remote communication. This project was approved by the institutional quality improvement performance registry process. Fisher exact, Wilcoxon test, and descriptive statistics were used for analysis.
Sample data for 300 patients revealed baseline demographic information for study population’s average age of 64 years and 43% were female. The number of clinical touches on predicting HbA1c control was not found to be statistically significant (P = 0.1582). However, there was a significant association for select medications when evaluated in combination with frequency of clinical touches to predict control. Insulin was the only agent that when evaluated solely resulted in a significantly lower HbA1c (p=0.03).
Sample population data shows that increased touches did not predict improved HbA1c values, however it could be considered that less controlled HbA1c were being followed more frequently and thus altering outcomes. Additional evaluation is needed to more closely investigate the combination of agents.

Disclosure
A. Vascimini: None. T. Sullivan: None. S.D. Curtis: None. C.E. DeRemer: Advisory Panel; Self; Bristol-Myers Squibb. Speaker’s Bureau; Self; Bristol-Myers Squibb, Pfizer Foundation. Stock/Shareholder; Self; Portola Pharmaceuticals, Inc.
2252-PUB: Fetal Cardiac Evaluation by Ultrasound to Assess Pregnancies Complicated by Maternal Diabetes
Authors: LEE-TANNOCK ALISON , HAY KAREN , KUMAR SAILESH 
Published: June 2020

Objectives: To evaluate fetal and neonatal cardiac morphology by echocardiography in pregnancies complicated by diabetes compared to normal healthy controls using ultrasound.
Methods: Fetal echocardiography was performed in 121 women with uncomplicated singleton pregnancies and 50 women with diabetes in pregnancy. The women underwent ultrasound scans every four weeks from enrolment (between 18-28 weeks gestational age) until delivery. Neonatal echocardiography was performed on the offspring. M-mode assessment was used to assess interventricular septal (IVS) thickness, left ventricle diastolic dimensions (LVED), fractional shortening (FS), tricuspid annular plane systolic excursion (TAPSE) and mitral annular plane systolic excursion (MAPSE).
Results: There were differences in IVS thickness, LVED, FS and TAPSE values between women with uncomplicated pregnancies and women with diabetes in pregnancy. These differences persisted into the neonatal period.
Conclusion: M-mode is a simple ultrasound technique to assess fetal cardiac function. Maternal diabetes was associated with increased IVS thickness, and reduction in TAPSE and FS measures. Prognostic implications of these findings may be useful in assessing pregnancies complicated by maternal diabetes in addition to current ultrasound assessment of fetal size and Doppler studies of fetal vessels.

Disclosure
A. Lee-Tannock: None. K. Hay: None. S. Kumar: None.

Funding
Mater Health Services; Australasian Society for Ultrasound in Medicine