bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Early Biochemical Changes in the Diabetic Retina Using an Unbiased Proteomics Approach
Authors: WEBER SARAH R. , ZHAO YUANJUN , BARBER ALISTAIR J. , HERNÁNDEZ CRISTINA , SIMÓ-SERVAT OLGA , GARDNER THOMAS W. , SIMÓ RAFAEL , SUNDSTROM JEFFREY M. 
Published: June 2018

Diabetic retinopathy (DR) remains a leading cause of blindness in developed countries. Current treatments target late stages of DR when vision has already been affected. The current study used an unbiased proteomic approach to gain a better understanding of early DR pathogenesis prior to clinically detectable microvascular lesions. During these early DR stages, neurodegeneration occurs and is marked by glial activation throughout the neuroretina. As glial activation increases, glial fibrillary acidic protein (GFAP) is upregulated and can be visualized histologically. Postmortem retinas from diabetic donors were divided according to the presence of abundant (n=5) or minimal (n=5) GFAP immunoreactivity and were compared to retinas from nondiabetic donors with no known ocular pathologies (n=10). Retinal lysates from each group were pooled and run on an SDS-PAGE gel. Bands were analyzed sequentially by LC/MS using an Orbitrap Mass Spectrometer. A total of 2,190 proteins were identified across all groups. Pathway activation analysis was performed via Ingenuity Pathway Analysis. Pathways were subsequently grouped into broader functional categories based on the existing literature. Differential pathway analysis revealed significant differences between diabetic retinas with abundant vs. minimal GFAP immunoreactivity. Of particular interest are those pathways that function in both neuroprotective/neurodegenerative and angiogenic pathways, as they may represent a link between early and late diseases stages. Antioxidant/anti-inflammatory pathways, cell survival and apoptosis pathways, and autophagy also appear to play a role. Future studies will be required to confirm and extend these findings. Close analysis of these signaling changes may permit the development of preventive and interventional strategies for use in the early stages of DR, before overt microvascular damage or vision loss occurs.

Disclosure
S.R. Weber: None. Y. Zhao: None. A.J. Barber: None. C. Hern ndez: None. O. Simó-Servat: None. T.W. Gardner: Research Support; Self; Novo Nordisk A/S. R. Simó: None. J.M. Sundstrom: None.
Progressive Improvement in Endothelial Nitric Oxide Release due to Synthase Dimer Formation with LDL Reductions below 70 mg/dL during Hyperglycemia
Authors: MASON R. PRESTON , DAWOUD HAZEM E. , SHERRATT SAMUEL , MALINSKI TADEUSZ 
Published: June 2018

In diabetes, endothelial cell (EC) dysfunction is characterized by reduced nitric oxide (NO) release and increased nitroxidative stress due to NO synthase (eNOS) dimer uncoupling. Reductions in LDL improve EC function but the effect is not well understood at levels below the target of 70 mg/dL. We measured NO and peroxynitrite (ONOO−) release as well as eNOS dimer formation in ECs under hyperglycemic conditions following progressive reductions of LDL in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with LDL at concentrations ranging from 150 to &lt;10 mg/dL with high glucose (250 mg/dL). Cells were stimulated with calcium ionophore, and assayed for NO and ONOO− release using porphyrinic sensors. eNOS dimer levels were measured using immunochemical approaches. Results showed that reductions in LDL levels had a disproportionate benefit on endothelial NO and ONOO− release below 70 mg/dL. A reduction in LDL levels from 70 to &lt;10 mg/dL produced a 181% increase in NO release (163 ± 18 to 458 ± 34 nM; p&lt;0.0001) and 116% decrease in ONOO− release (393 ± 27 to 182 ± 23 nM; p&lt;0.0001), corresponding to a 513% increase in the NO-to-ONOO− release ratio (0.42 ± 0.04 to 2.56 ± 0.40; p&lt;0.0001), a comprehensive indicator of EC function. These changes also correlated with increased eNOS dimer formation by 819%. By contrast, only a modest 27% change in EC function was observed as LDL levels were reduced from 150 to 70 mg/dL with regard to the NO-to-ONOO− release ratio. In the absence of hyperglycemia, the benefits of LDL lowering on EC function and eNOS dimerization were also very evident, but to a lesser extent. Thus, progressive improvements in endothelial NO bioavailability and eNOS dimer formation were observed at LDL levels below 70 mg/dL to &lt;10 mg/dL. These in vitro data suggest that reductions in LDL to very low levels may be effective in reversing EC dysfunction for the diabetic patient.

Disclosure
R. Mason: Research Support; Self; Amarin Corporation, Amgen Inc., Pfizer Inc.. Consultant; Self; Amarin Corporation. Speaker's Bureau; Self; Pfizer Inc.. H.E. Dawoud: None. S. Sherratt: None. T. Malinski: None.
A Neural Signature of Metabolic Syndrome—Preliminary Results
Authors: KOTKOWSKI EITHAN , FRANKLIN CRYSTAL , FOX PETER T. 
Published: June 2018

As of 2012, metabolic syndrome (MetS) has been estimated to impact 34.7% of the U.S. population (Aguilar, 2015). Meeting the criteria for MetS increases one’s risk for developing cardiovascular disease and type 2 diabetes mellitus (T2DM). However, only recently have researchers begun to probe its effects on brain structure and function. Recent studies have shown that in humans, increased levels of obesity and hyperglycemia are correlated with decreased executive function, processing speed, memory, as well as higher incidences of depression, among others (Yates, 2012). Evidence also suggests that effects of MetS and neurocognitive dysfunction are bidirectional and complex, with genetic, environmental, and behavioral causes playing an important role (Biessels, 2014). In our study, we use voxel-based morphometry (VBM), a well-established structural MRI imaging analysis, to investigate regional gray matter atrophy differences between age- and sex-matched healthy controls (n = 108) and individuals meeting the International Diabetes Federation criteria for MetS (n = 108) from a homogenous Mexican-American cohort. We find that, indeed, there is a significant difference in gray matter density between individuals meeting the criteria for MetS and their age- and sex-matched healthy controls with statistically significant involvement in the following brain regions: bilateral caudate nuclei, orbitofrontal cortex, right parahippocampus/amygdala, right posterior insula, and posterior cerebellum. Additionally, when regressing out key components of MetS such as waist circumference and obesity, we find diverging gray matter atrophy patterns suggesting differential involvement of MetS components on gray matter structure.

Disclosure
E. Kotkowski: None. C. Franklin: None. P.T. Fox: None.
Insulin or Metformin for Glucose Control during Wound Healing in Diabetes?
Authors: MROZIKIEWICZ-RAKOWSKA BEATA , MIECZKOWSKI MATEUSZ , SIWKO TOMASZ , BUJALSKA-ZADROZNY MAGDALENA , GRZELA TOMASZ , WOLINSKA RENATA , DE CORDE ANNA E. , FOLTYNSKI PIOTR , CZUPRYNIAK LESZEK 
Published: June 2018

Good glycemic control is crucial for the proper wound healing in diabetes. It is not clear whether there is any additional effect on wound healing of any antidiabetic drugs beyond improvement in glucose control. We conducted an experimental study aiming at assessing the effect of insulin and metformin on the wound healing. The study was performed in 45 male Wistar rats with streptozotocin-induced diabetes divided into 3 groups: group 1 received human NPH insulin intraperitoneally (5 j.m./kg b.w.) once daily, group 2 received metformin intragastrically (500 mg/kg b.w.) once daily and group 3 (controls) were given saline intraperitoneally. The treatment goal was to achieve blood glucose levels of 350-450 mg/dl in order to reflect hyperglycemic conditions often associated with wound development. After 30 days of antidiabetic treatment the rats had the thin layer of the skin cut out from the dorsal skin 2x2 cm. The wounds were assessed every 3 days with digital photography and wound biopsy. The wounds healing was followed-up for 9 days. Mean blood glucose levels in all groups after 30 days of treatment and during wound healing follow-up ranged 350 and 450 mg/dl. After 3 days healing in the rats treated with insulin was more advanced than in the control group, and it was more advanced than in the metformin group after 6 and 9 days. There were no differences between the metformin and control groups at any stage of the study. Wound tissue samples taken from the insulin treated animals presented with significantly lower level of inflammatory infiltration than those obtained from the rats treated with metformin. Immunohistochemical assessment showed the greatest density of centers of profileration in insulin treated animals.
In conclusion, insulin treatment was more beneficial than metformin for the wound healing process in animal model. As the observations were made at a similar level of hyperglycemia in all groups, it might be speculated that there is an additional effect of insulin on wound healing beyond glucose lowering action.

Disclosure
B. Mrozikiewicz-Rakowska: None. M. Mieczkowski: None. T. Siwko: None. M. Bujalska-Zadrozny: None. T. Grzela: None. R. Wolinska: None. A.E. de Corde: None. P. Foltynski: None. L. Czupryniak: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Merck & Co., Inc., Polpharma, Servier.
3D Microstructural Fiber Tracking of the Human Calf Muscles in Individuals With and Without Type 2 Diabetes during Rest and Exercise
Authors: EDALATI MASOUD , SORENSEN CHRISTOPHER J. , HASTINGS MARY , ZAYED MOHAMED A. , MUELLER MICHAEL J. , ZHENG JIE 
Published: June 2018

Aim: This work explores underlying microstructural fiber differences in the calf muscles of individuals with and without type 2 diabetes mellitus (DM) at rest and during an isometric exercise.
Methods: Twenty-one subjects were examined in a 3T MRI scanner. Two groups were tested: 8 participants without DM (WDM) and 13 participants with DM. We used a custom-made MRI compatible ergometer that consisted of a brake-like pedal with an adjustable pressure gauge. Diffusion tensor imaging was performed on calf at rest and during a plantarflexion exercise. Regions of interests (ROI) were manually drawn on medial and lateral gastrocnemius (MG and LG), as well as on soleus (SOL).
Results: In the MG, the fiber length changes (%) were -29.07±6.71 for the WDM, and -52.53±15.for the DM group (P&lt;.001). Exercise fiber density (P&lt;.01) and angle (P&lt;.05) changes were also significantly different between groups. The DM resulted in more fiber disarrays with loss of fiber during exercise (Fig 1).
Conclusions: While more changes in the fiber indices were observed in the DM during exercise, significant difference was shown in the MG muscle. These changes may reflect diabetic damage by altering muscle microstructure.

Disclosure
M. Edalati: None. C.J. Sorensen: None. M. Hastings: None. M.A. Zayed: None. M.J. Mueller: None. J. Zheng: None.
The Roles of NLRP3 Inflammasome and ADAR1 in Diabetic Foot Ulcer
Authors: WANG FANG , ZHAO LILING , YANG WENJUN , HE HONGHUI , MO ZHAOHUI 
Published: June 2018

Infected diabetic foot ulcer (DFU) is an important problem because it is a limb or even life threatening, and burdens a great financial load to the community. It’s shown that circulating inflammatory proteins are reputed to be of poor value for diagnosing DFU as lack of specificity. Therefore it's necessary to investigate newer discussed inflammatory parameters. NLRP3 inflammasome, a multiprotein complex consists of NLRP3, ASC and pro-caspase-1 and controls the production of IL-1β and IL-18, is an important contributor to the development of type 2 diabetes. The RNA-specific adenosine deaminase (ADAR1) is interferon-inducible double stranded (ds) RNA-binding protein, which is demonstrated to inhibit the production of type I interferons and various proinflammatory cytokines such as TNF-a and IL-6. But little is known about the ex vivo profile of NLRP3 inflammasome and ADAR1 in DFU. On this basis the aim of our study was to evaluate the role of NLRP3 inflammasome and ADAR1 in subjects with DFU in comparison with subjects without DFU. We completed a study including 20 healthy volunteers, 20 newly diagnosed type 2 diabetic (T2D) patients and 30 DFU patients (wagner2-4). Then peripheral blood mononuclear cells were collected from all subjects and NLRP3, ASC, Caspase-1, ADAR1 contents were detected by real-time PCR. The results showed that mRNA of NLRP3, ASC, Caspase-1 in T2D patients were significantly higher than those of healthy persons, while 2-fold lower than DFU patients (both P &lt; 0.05); ADAR1 mRNA in T2D patients were significantly higher than those of healthy persons (P &lt; 0.05). Interestingly, however, ADAR1 mRNA in DFU patients were decreased by 3-fold compared with T2D (P &lt; 0.05), indicating that ADAR1 is increased in low-grade inflammation state but decreased in severe infectious state. This study suggests that NLRP3 inflammasome and ADAR1 may be useful markers to diagnose and follow the DFU. Further investigation is needed and it will be interesting to investigate the connection between them.

Disclosure
F. Wang: None. L. Zhao: None. W. Yang: None. H. He: None. Z. Mo: None.
Evaluating Evidence-Based Strategies to Build and Support Lifestyle Change Programs for People at High Risk for Type 2 Diabetes
Authors: MENSA-WILMOT YVONNE , BOWEN SHELLY-ANN , BROWN ROSS I. , BONNER TIMETHIA , FARRIS KIMBERLY D. , RUTLEDGE GIA E. 
Published: June 2018

This study discusses preliminary outcomes from a subset of national grantees implementing evidence-based engagement strategies to scale the National Diabetes Prevention Program (National DPP) and reach people at risk for type 2 diabetes, including population subgroups who experience health or socioeconomic disparities. Quantitative and qualitative analyses were conducted using progress reports submitted in years 1 and 2 by grantees (health departments in 17 states and 4 large cities). Evaluation reports were analyzed using MAXQDA software to identify facilitators and barriers to implementing these strategies. Grantees worked to increase prediabetes screening, testing, referral, and enrollment among vulnerable, high-risk participants. Major strategies implemented included (1) developing tailored marketing plans to reach and engage persons with prediabetes, (2) implementing culturally tailored media campaigns, and (3) funding lifestyle coach trainings and professional development opportunities on motivational interviewing. Media metrics show &gt; 2 million people were reached (increase of 794% from baseline) and &gt; 17,000 people (increase of 86% from baseline) with prediabetes enrolled in programs. Facilitators included partnerships, technical assistance to build capacity, and development of referral policies. Barriers included lack of referral processes, unclear communication among partners, and language barriers in some populations. As grantees worked to increase awareness of prediabetes and extend the reach of the National DPP, they created a network of partners, engaged community stakeholders, and developed activities to sustain the programs by leveraging existing resources.

Disclosure
Y. Mensa-Wilmot: None. S. Bowen: None. R.I. Brown: None. T. Bonner: None. K.D. Farris: None. G.E. Rutledge: None.
I Wanted Diabetes Out—Lived Experiences of Diabetes Burnout from Bloggers with Type 1 Diabetes
Authors: ABDOLI SAMEREH , VORA AMIT C. , HESSLER DANIELLE M. , STUCKEY HEATHER L. 
Published: June 2018

Objective: To define and understand diabetes burnout through thematic analysis of narrative posts, written by adults with type 1 diabetes (T1D), published in publicly available blogs.
Research Design and Methods: A qualitative thematic analysis of 35 posts published in 21 blogs from the U.S., UK, and Ireland, written by adults with T1D, provided the basis for definition(s) of diabetes burnout. Data management (Nvivo 11 Pro) and analysis included three phases: immersion, reduction, and interpretation (kappa=.91).
Results: Findings included five main themes that described diabetes burnout: (1)Burnout is a “detachment” from diabetes care; (2) the “demanding life” of diabetes leads to burnout; (3) struggling with “perfect” numbers adds to burnout; (4) “life events” are catalysts to burnout; (5) and overcoming burnout is like “climbing out of a difficult hole.”
Conclusions: Analysis of blogs provided unique insights into the concept of diabetes burnout. Five themes were identified that ranged from detachment from diabetes care to difficulties in overcoming diabetes. These data provide a next step into understanding diabetes burnout and factors that may co-occur. Further research needed to advance science of diabetes burnout to improve quality of care and quality of life of individuals with diabetes.

Disclosure
S. Abdoli: None. A.C. Vora: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis, Janssen Pharmaceuticals, Inc. D.M. Hessler: Consultant; Self; Eli Lilly and Company. H.L. Stuckey: Consultant; Spouse/Partner; Calibra Medical, Eli Lilly and Company. Research Support; Spouse/Partner; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc..
Diabetes Self-Management Education via Telemedicine in the United States Air Force
Authors: WATSON NINA , ACUNA DORIS G. , WARDIAN JANA L. , COBB ELLEN C. , BEAVERS DAVID , SAUERWEIN TOM J. 
Published: June 2018

Diabetes Self-Management Education (DSME) is recommended for patients with a new diagnosis or without prior diabetes education. However, not all Military Treatment Facilities (MTFs) have capacity to provide this resource to patients, which creates a disparity in healthcare. The Diabetes Center of Excellence (DCOE) has an ADA-recognized DSME program and potential to fill this gap through DSME via telemedicine. The Military Interagency Satellite Training (MIST) system, which utilizes satellite technology to broadcast one-way video and two-way audio to distance learners, is available at all MTFs. To test the concept, DSME was broadcast to Randolph Air Force Base (RAFB) from October 2016-October 2017. During this time, 181 patients enrolled in DSME classes; 127 were DCOE patients and 54 were from RAFB. Among data collected were pre/post patient knowledge tests and the validated 17-item Diabetes-related Distress Scale (DDS-17). Knowledge significantly increased from baseline to Class 4. Few patients completed all 4 classes and 6 month follow-up (n=16). Patients had an increase in all DDS-17 domains at the completion of Class 4; however, by 6 months, distress returned to baseline levels. Patient satisfaction surveys were completed at DCOE (n=429) and RAFB (n=227) at each encounter and provider satisfaction surveys were collected from RAFB facilitators. Patients at RAFB reported higher satisfaction (99.1%) than DCOE patients (97.2%). In fact, most measures of satisfaction were higher in RAFB patients than DCOE patients. Moreover, facilitators expressed high satisfaction with DSME via MIST and all facilitators were willing to conduct more classes in this format. Initiation of the DSME Telehealth program presented challenges, especially in technology-related issues and documentation at 6 months. The pilot program allowed the DCOE to gain valuable feedback from our remote site. Technology issues have largely been resolved enabling us to provide an even better experience to our new sites in 2018.

Disclosure
N. Watson: None. D.G. Acuna: None. J.L. Wardian: None. E.C. Cobb: None. D. Beavers: None. T.J. Sauerwein: Speaker's Bureau; Self; Merck & Co., Inc., AstraZeneca.
Employee Health: Diabetes Self-Management with Wireless Meter
Authors: BRUCH JOHN , STANCIL MICHELLE D. , ODOM JESSICA M. , NELSON BRYCE A. , REULBACH LINDSAY S. , RUSS-SELLERS REBECCA , BURNS ALYSON GHIZZONI , LINDHOLM MAINE R. , DAWSON JONDA , SCHWECKE NATHAN A. 
Published: June 2018

In 2014, Greenville Health System spent more than double on employees with A1c greater than 7.5% compared to employees with A1c less than 7.5%. Visits with a primary care physician every three months may be inadequate to meet the needs of a patient with uncontrolled diabetes. The goal of the study was to improve care for a targeted population of employees of a large health care system with type 1 or 2 diabetes. The intervention combined diabetes education, telehealth, a wireless enabled meter, and algorithms for medication adjustments.
Methods: Fifty patients were given a wireless enabled meter that links to secure portal for the healthcare professional, the patient, and a support person. The primary objective was to achieve a 15 percent reduction in patients’ average baseline A1c. Secondary objectives included improving patient’s understanding of diabetes and self-management of diabetes, increasing adherence rates of diabetes monitoring and medication utilization, decreasing rates of hypoglycemic or hyperglycemic events, and reduce overall cost of healthcare. Patients were contacted by a diabetes educator every 2-4 weeks. A medication algorithm was used to titrate insulin and non-insulin medications and initiate additional treatments.
Results: Patients were followed for an average of 27.6 months. Baseline A1c average of 10.248 was reduced to an average of 8.392 (absolute reduction of 1.856 or 18% reduction from baseline). Compared to baseline, at 12 months patients reported improvement in their self-rated diabetes knowledge, self-monitoring behaviors, and self-management behaviors. Participants increased their outpatient visits with primary care providers and Endocrinology. Average cost for both endocrinology and PCP visits decrease from pre-enrollment to one year post enrollment.
In conclusion, by combining diabetes education, medication algorithms, and remote glucose monitoring, participants improved their knowledge of diabetes and self-care and experienced improved glycemic control.

Disclosure
J. Bruch: None. M.D. Stancil: None. J.M. Odom: None. B.A. Nelson: Speaker's Bureau; Self; Dexcom, Inc.. L.S. Reulbach: None. R. Russ-Sellers: None. A. Ghizzoni Burns: None. M.R. Lindholm: None. J. Dawson: None. N.A. Schwecke: None.