bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keap1-Mediated Nrf2 Dysfunction as a Source of Oxidative Damage in Human Diabetic Wounds
Authors: DAVID JOSHUA A. , VILLARREAL-PONCE ALVARO P. , ABDOU SALMA A. , SULTAN DARREN L. , RIFKIN WILLIAM J. , KWONG JENNIFER , RABBANI PIUL S. , CERADINI DANIEL 
Published: June 2018

Purpose: Despite advancements in disease management and wound therapies, chronic diabetic ulcers represent the leading cause of non-traumatic lower extremity amputations in the United States. The Nrf2 master antioxidant transcription factor has emerged as a promising target for combatting the oxidative stress underlying these wounds. We have previously implicated Keap1-mediated Nrf2 dysfunction in delayed diabetic wound healing, and as a therapeutic target, in mice. However, whether these findings extend to human diabetic wounds remains unknown.
Methods: Intact skin (S) and wound tissue (W) was obtained from diabetic (D) and nondiabetic (ND) patients, and analyzed for reactive oxygen species (ROS) end products (8-OhDG DNA assay), and with immunohistochemistry (IHC), qPCR (gene expression), and western blot (protein expression). Student’s t-tests were used for statistical analysis.
Results: Both DS and DW contained more than 2-fold ROS end products, respectively, compared to NDS and NDW (2.344 vs. 1.117 ng/mL and 4.648 vs. 1.866 ng/mL, p&lt;0.008). DS and DW exhibited 2-fold and 2.5-fold decreases in epidermal Nrf2 staining, respectively, compared to NS and NW (p&lt;0.001). Keap1-the cytoplasmic Nrf2 repressor-was overexpressed in DW when compared to NDW (p&lt;0.04). DW showed a 75% reduction in nuclear Nrf2 protein expression (p&lt;0.02) as compared to NDW. DW also exhibited a 25% relative reduction in gene expression of MnSOD, a key Nrf2 downstream antioxidant enzyme, and 5-fold decrease in epidermal cytoplasmic MnSOD staining compared to NDW, p&lt;0.03.
Conclusion: Here, we implicate Nrf2 dysfunction in impaired redox homeostasis and consequent oxidative damage in both human diabetic skin and diabetic wounds as compared to nondiabetics. We also identify Keap1 as a likely mediator of impaired healing in diabetic wounds. These results recapitulate our previous findings in mice, further validating this critical pathway as a promising target for understanding and treating diabetic wound healing.

Disclosure
J.A. David: None. A.P. Villarreal-Ponce: None. S.A. Abdou: None. D.L. Sultan: None. W.J. Rifkin: None. J. Kwong: None. P.S. Rabbani: None. D. Ceradini: None.
Bridging the Gap of Diabetes Education—The IDF School of Diabetes
Authors: PATHAN SAMEER , OHLROGGE ANNE WIEBKE , MALANDA BELMA , SUNG ELS , PIEMONTE LORENZO 
Published: June 2018

Background: In 2017, 425 million people were affected worldwide by diabetes. The rapid global growth of the disease shows that there is an urgent need to upgrade the capacity of healthcare workers to educate, manage and treat people with diabetes. Thus, the International Diabetes Federation (IDF) launched the IDF School of Diabetes in Nov. 2016.
Aim: The online IDF School of Diabetes aims to meet the global demand in diabetes education by offering up-to-date and evidenced-based diabetes education available globally.
Methods: IDF conducted a needs assessment, based on a survey amongst the Diabetes Education Network for Health Professionals (D-NET) 10,000 members from 172 countries. In response a set of courses were produced, combining knowledge from world-leading specialists and renowned experts. The curricula are designed to deliver international standards of diabetes care, management and prevention, targeted at Diabetes Educators, PCPs and GPs and Specialists. Furthermore, short courses on Prevention, Diabetic Retinopathy and CVD are offered for free. The IDF School is accredited by the European Accreditation Council for Continuing Medical Education and thus, can grant CMEs to course participants.
Results: The latest statistics, collected in January 2018, indicated that over 3500 members are using the IDF School of Diabetes. In general, Healthcare Professionals registered on the platform than Non-Healthcare Professionals. The geographical reach of the platform extends to 170 countries, with middle-income countries taking up the majority of these registrations.
Discussion: The IDF School offers an opportunity for all people involved in diabetes care to access unique and convenient education that is vital in tackling the global health crisis of diabetes. To date, the platform has received widespread interest for the open access content and paid online courses. This encouraging data provides a firm basis to continue development of further content that will help in the prevention, care, and management of diabetes.

Disclosure
S. Pathan: None. A. Ohlrogge: None. B. Malanda: None. E. Sung: None. L. Piemonte: None.
Diabetes Knowledge and Numeracy among Under- or Uninsured Latinos with Type 2 Diabetes
Authors: HUANG YA-CHING , GARCIA ALEXANDRA A. , ZUNIGA JULIE A. 
Published: June 2018

For people with diabetes, low literacy and low numeracy are risk factors for poor diabetes outcomes. Diabetes Numeracy is a predictor of diet management and A1C. The purpose of this study was to analyze the relationship between diabetes knowledge and numeracy in Latinos with type 2 diabetes (T2DM). Participants (n=139) from 3 clinics for un- and underinsured people completed the Spoken Knowledge in Low Literacy for Diabetes (SKILLD, 11 open-ended items, possible scores = 0-11), Diabetes Knowledge Questionnaire (DKQ; 24 true-false items, possible scores = 0-24), and a short version of the Diabetes Numeracy Test (DNT, 5 open-ended items, possible scores = 0-5); higher scores indicated better knowledge or numeracy. We calculated descriptive and correlational statistics and estimated hierarchical regression models of diabetes numeracy with these sets of predicators: (1) demographic (age, gender, married, education, and acculturation); (2) SKILLD, DKQ, and DNT scores. Participants were predominately middle-aged (mean 48.3 ± 9.324 years), female (52.5%), married (65.5%), with an average of 9.13 years of education ± 4.62. Mean SKILLD score = 6.45 ± 1.65 (59% correct); DKQ score = 16.63 ± 2.81 (69%); and DNT score = 1.91 ±1.31 (38%). Years of education, SKILLD, and DKQ score were positively correlated to DNT scores. However, after controlling for demographic characteristics, only education and DKQ score were significant predictors of DNT scores in the hierarchical regression model. People with higher education level and DKQ score reported higher DNT. The entire regression model accounted for 25.7% of variance in DNT (F = 6.42, p &lt; .001). Participants in this study had low diabetes knowledge and very low numeracy. Focusing on numeracy (e.g., using food labels, calculating portion size, and interpreting medication labels), especially for the least educated, may provide the most benefit in behavior and outcomes. Future studies should examine numeracy as it relates to self-management behaviors and outcomes.

Disclosure
Y. Huang: None. A.A. Garcia: None. J.A. Zuniga: None.
Can Practice Redesign Improve Diabetes Self-Management Education (DSME) Referrals?
Authors: KRALL JODI , KANTER JUSTIN , ARENA VINCENT C. , RUPPERT KRISTINE , SOLANO FRANCIS X. , SIMINERIO LINDA M. 
Published: June 2018

DSME is considered an essential component of diabetes care, but participation is abysmal. Referral processes and traditional delivery models may serve as barriers. The purpose of this study was to deploy a model that relied on elements of the patient-centered medical home (PCMH) and direct delivery of DE services in primary care (PC) and evaluate its impact on PC provider (PCP) referrals to DSME.
Methods: Using a non-randomized controlled design, DEs and PC practices were assigned to the intervention group (IG; 3 DEs, 6 practices) or control (2 DEs, 6 practices). Practices in the IG were introduced to DSME Position Statement (PS) referral algorithm and PCMH elements and negotiated application for their practice, including frequency of direct delivery of DSME in PC. Traditional DSME delivery (no direct link between DE and PC) served as control. To examine DSME referrals, data were extracted from medical records for all patients with DM, age 18-75y, who presented to their PCP over 12 months (n=4,508; 60.7% IG) and compared between study groups.
Results: Mean age was 59.8y, and primarily male 51.2%. The IG referred a higher percentage of patients compared to the control group (12.6% vs. 7.9%; p&lt;0.0001). Using logistic regression modeling, it was found that after adjusting for age, gender, race, A1c, obesity, and micro/macrovascular comorbid conditions, the IG was 1.9 (Confidence Level 1.5-2.4) times more likely to refer patients to DSME. Other factors found to predict referrals were female (Odds Ratio=1.3, CL 1.1- 1.6), obesity (OR=2.7, CL 2.2-3.3) and higher A1c (OR=3.2, CL 2.6-3.9). Older patients were less likely to receive a referral (OR=0.99, CL 0.978-0.995).
Conclusions: Findings suggest that the intervention positively influenced DSME referral rates within PC, a critical step towards improving patient participation in DSME and meaningful improvements in diabetes outcomes. Further study of DSME referral types, PS referral algorithm influence, and utilization patterns is warranted.

Disclosure
J. Krall: None. J. Kanter: None. V.C. Arena: None. K. Ruppert: None. F.X. Solano: None. L.M. Siminerio: None.
Effects of a Primary Care–Based Chronic Care Model on Diabetes Self-Management, Diabetes Distress, and Health Care Experience
Authors: FORTMANN ADDIE L. , PRECIADO JESSICA L. , WALKER CHRIS , MORRISEY ROBIN , BARGER KELLY , MILLS DEIRDRE , ROBACKER MAIRE , PHILIS-TSIMIKAS ATHENA 
Published: June 2018

By 2034, the number of U.S. individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Current healthcare systems are often not equipped to support the growing diabetes population, and many individuals are not achieving clinical targets necessary for preventing diabetes complications and for improving long-term survival. To address this need, an innovative, Chronic Care Model (CCM)-based care management program was developed that used clinical risk stratification, standardized decision support tools, RN + health coach + PCP team-based care, and a depression care manager. N=236 T1D and T2D (96%) patients (M age = 61.9 ± 11.4 years; 51% male) were enrolled at a San Diego clinic that includes diverse payors and an integrated PCP group. This care management program was previously shown to achieve significant improvements in cardiometabolic outcomes (HbA1c, LDL-c) and health care costs relative to usual care at 1-year. The present analysis evaluated effects on diabetes self-management (Summary of Diabetes Self Care Activities) and distress (Diabetes Distress Scale), and patients’ experience with CCM-based healthcare delivery components (Patient Assessment of Chronic Illness Care). Statistically significant improvements were observed in healthful eating (5 vs. 4 days/week), exercise (5 vs. 3), blood glucose monitoring (5 vs. 4), foot-checking (5 vs. 3), and diabetes distress (14% vs. 24% with moderate distress) over 12 months (ps &lt; .05). Patients’ perceptions of follow-up/care coordination, support for patient activation and self-management, and delivery design also improved over this period (ps &lt; .05). Taken together, this population-based care management program represents an approach that can improve clinical, behavioral, psychosocial and cost outcomes, and health care delivery experience for people with diabetes in the primary care environment.

Disclosure
A.L. Fortmann: None. J.L. Preciado: None. C. Walker: None. R. Morrisey: None. K. Barger: None. D. Mills: None. M. Robacker: None. A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca.
An Evaluation of the Diabetes Conversation Map Program—Health Outcomes and Health Care Utilization during a Four-Year Follow-Up
Authors: SRULOVICI EINAV , LEVENTER-ROBERTS MAYA , CURTIS BRADLEY , HE XUANYAO , HOSHEN MOSHE B. , ROTEM MINA , GOFER ILAN , SHADMI EFRAT , KEY CALANIT , LEVIN-IAINA NOMY , STRIZEK ALENA , FELDMAN BECCA S. 
Published: June 2018

Background: Diabetes Conversation Map™ (Map™) is a global education program that engages patients with type 2 diabetes Mellitus (T2DM) in group-based discussions on diabetes-related topics. This study compares outcomes annually between participants and matched controls over a 4-year period.
Methods: This was a retrospective cohort study of 11,053 Clalit Health Services members with T2DM who enrolled in the Map™ program between 1.1.2010 and 4.1.2016. The associations between program participation and annual laboratory test results (HbA1c, glucose and LDL levels), health behaviors (frequency of glucose and HbA1c testing), and healthcare utilization (hospital, physician and specialist visits) were assessed between cases and controls using regression analysis.
Results: The Map™ group had significantly improved HbA1c, glucose, and LDL levels and more frequent blood glucose testing each year up to 36 months post-enrollment compared to matched-controls. They also had significantly fewer annual primary care visits but more annual ophthalmologist and nutritionist visits up to 24, 36, and 48 months post-enrollment, respectively, compared to matched-controls. The annual frequency of hospital admissions and length of hospital stay was lower up to 36 and 48 months post enrollment, respectively, in the Map™ group compared to matched-controls.
Conclusions: Participation in the Map™ program was associated with improved clinical outcomes, behaviors, and healthcare utilization for at least 24 months, suggesting that an intervention booster may be needed beyond this time period. These findings support the significant impact of the Map™ program on the lives of patients with T2DM.

Disclosure
E. Srulovici: None. M. Leventer-Roberts: None. B. Curtis: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. X. He: None. M.B. Hoshen: None. M. Rotem: None. I. Gofer: None. E. Shadmi: None. C. Key: None. N. Levin-Iaina: Employee; Self; Eli Lilly and Company. A. Strizek: None. B.S. Feldman: None.
Novel Insulins and Fixed-Ratio Combinations—Effect of Case-Based Online Education on Physician Knowledge and Competence
Authors: PHILIS-TSIMIKAS ATHENA , GRIFFITH GILLIAN A. , TRIER JOACHIM 
Published: June 2018

Purpose: To determine if case-based online medical education for diabetologists/endocrinologists (diabs/endos) and primary care physicians (PCPs) can improve knowledge and competence regarding the role of novel insulins and their fixed-ratio combinations (FRCs) in treatment strategies for patients with T2DM.
Methods: This educational initiative incorporates branching logic to individualize clinical problem-based learning via case-based instruction. Each of two patient cases included both clinical decision questions (CDQs) and knowledge assessment questions (KAQs). Tailored feedback and clinical consequences were provided for CDQs and percent of correct answers on second attempt after feedback was recorded. Pre- and post-assessment choices were compared for the KAQs and a paired 2-tailed t-test was used for statistical analysis. Effect sizes were calculated with Cohenߣs d. The activity launched March 24, 2017; data were collected until April 24, 2017.
Results: Participation in the activity significantly advanced knowledge/competence of diabs/endos (n=115) and PCPs (n=568). 43%-81% of diabs/endos and 27%-75% of PCPs answered a CDQ correctly on the first attempt while 16%-47% of diabs/endos and 19%-60% of PCPs improved their clinical decisions after receiving tailored feedback with an overall large effect size of 1.88 (diabs/endos) and 1.87 (PCPs). Correct responses of KAQs were 2%-13% higher for diabs/endos and 5%-28% for PCPs after activity completion with an overall small effect size of 0.085 (diabs/endos) and 0.1(PCPs).
Conclusions: Participation in this innovative, case-based CME activity resulted in improved competence and knowledge regarding the utility of novel insulins and their FRCs for patients with T2DM. Despite notable improvement, both diabs/endos and PCPs would benefit from additional education on the optimal integration of these novel insulin formulations into treatment regimens for their patients with T2DM.

Disclosure
A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca. G.A. Griffith: None. J. Trier: None.
Free Diabetes Smartphone Apps—Downloads and Rankings 2016 vs. 2017
Authors: WU GLORIA , NGO VY-VY 
Published: June 2018

Purpose: Do the frequency of downloads of free diabetes smartphone droid apps change from year to year?
Methods: Using Google playstore, we found the most popular apps in 2017. For 2016 apps, we used our 2016 data 1 from the Google playstore. The 11 most popular free apps in 2016 and 2017 were compared.
Results: The change in app ranking were associated with "pay for premium features (PPF)" in 2017. The app, mySugr remains no. 1 in terms of number of downloads, due to fewest changes in PPF. Diabetes M went from no. 5 in 2016 to no. 8 in 2017, due to PPF. Glucose Buddy remained at no. 4 in the two years. Blood Glucose Tracker went from 2 to 11 in two years due to high cost PPF. Of the most popular apps in 2017, Diabetes Plus is only free on android. In 2016, only 2 are for children:Carb Counting with Lenny and mySugr Junior. As of 2017, mySugr Junior no longer exists. None of the 2017 or 2016 apps have glycemic index. All apps in 2017 require email login. 4/11 apps record height and weight in 2017. 3/11 apps do not record blood pressure in 2017. 5/6 apps were journal based vs. 12/12 apps in 2017.
Conclusion: The popularity of apps change greatly in 24 months. Patients and MDs have a common goal in seeking useful mobile apps for diabetes self-management.

Disclosure
G. Wu: None. V. Ngo: None.
Do Free Smartphone Apps Have Features of the Diabetes Self-Management Education/Support Guidelines?
Authors: WU GLORIA , NGO VY-VY 
Published: June 2018

Purpose: Assessing free diabetes smartphone apps in 2016 and 2017 for popularity and features of the Diabetes Self Management/Education Guidelines (DSME) from the ADA.
Methods: Google analytics were used to evaluate the 11 most popular apps for 2016 and 2017. The apps were then assessed with the ADA's DSME guidelines. The 2016 app ranking was taken from our unpublished data. 1
Results: While 8/11 had HbA1c in 2016, this category improves to 100% in 2017. In 2016 v 2017: 6/11 vs. 10/11 used calorie counting. For triglycerides and lipids, both in 2016 and 2017, only one app features this category. For psychological moods, there were two apps with this feature in 2016 but only one in 2017. Goal setting in 2016 v 2017: 4 vs. 5.
Conclusions: The apps from 2017 are greatly improved over 2016. All except one app show cal/carbs, HbA1c/FBS, medical diary/log. However there is still room for improvement for the categories of Triglycerides/lipids, Psychological mood, BMI and Goal setting. We, as physicians, look forward to more robust free apps for diabetic patients.
Reference: Gao M, Wu G, Bautista BM et al. "2016 Diabetes Smartphone Apps and Diabetes Self Management Education/Support Guidelines. Endocrine Society poster presentation, Orlando FL, April 3, 2017.

Disclosure
G. Wu: None. V. Ngo: None.
Exercise Prevents High-Fat Diet–Induced Impairment of Insulin-Induced Vasodilatation of Muscle Arterioles in Mice by Browning Perivascular Adipose Tissue of Mice
Authors: BOA BEATRIZ C.S. , FERRÃO FERNANDA M. , GONZAGA ISABELA M. , PINTO LUIS FELIPE R. , VAN HINSBERGH VICTOR W.M. , ERINGA ETTO C. 
Published: June 2018

Perivascular adipose tissue (PVAT) surrounds most arteries and enhances insulin-induced vasodilatation through local release of adipokines. Obesity impairs the vasoregulatory function of PVAT on insulin-induced vasodilation, thus contributing to cardiovascular risk. Exercise enhances insulin-induced vasodilatation, and we evaluated whether exercise preconditions the muscle microcirculation against HFD-induced impairment of insulin-induced vasodilatation. C57BL/6 mice were exercised for 4 weeks (EX), or fed a high fat diet (HFD) for 2 weeks. Exercise preconditioning was performed by exercising mice for 4 weeks prior to HFD treatment (EX+HFD) or before and during HFD (EX+HFD/EX). HFD increased femoral PVAT and exercise attenuated this effect [(Control (C) 9±1mg vs. HFD 64±7mg - p&lt;0.01) (EX+HFD 29±5mg; EX+HFD/EX 32±2mg; p&lt;0.01 vs. HFD)]. Insulin-induced vasodilatation (0.5 IU/kg i.p.) was evaluated in vivo in the cremaster muscle. HFD inhibited insulin-induced vasodilatation [C 22±5% dilatation; HFD -11±4.3% dilatation, p&lt;0.01 vs. C], but exercise precondition restored it [EX+HFD-24±5% and EX+HFD/EX-32±8.9% dilatation; p&lt;0.05]. Browning of adipose tissue improves insulin sensitivity and adipokine secretion, and we observed browning by an increase in the mRNA of the browning marker Ucp-1 in aortic PVAT [72% increase in EX+HFD/EX vs. C p&lt;0.01] and in brown adipose tissue [C 3±0.3; HFD 10±1; EX 8±0.9; *EX+HFD 19±2; *EX+HFD/EX 14±1.8; 2-Δct p&lt;0.01 vs. C]. mRNA of the vasoprotective adipokine adiponectin was increased in PVAT of EX and EX+HFD/EX mice (p&lt;0.vs. C, HFD and EX+HFD), while the inflammatory TNF-α was substantially decreased (HFD vs. C, EX+HFD and EX+HFD/EX vs. HFD; p&lt;0.05).
In conclusion, exercise reduces the HFD-induced increase in PVAT and preserves insulin-induced vasodilatation by increasing mitochondrial uncoupling and improving adipokine expression in PVAT.

Disclosure
B.C.S. Boa: None. F.M. Ferr o: None. I.M. Gonzaga: None. L.R. Pinto: None. V.W.M. van Hinsbergh: None. E.C. Eringa: None.