bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Association of Inflammatory Markers and Growth Factors with Type 2 Diabetes and Polyneuropathy—A Multimarker Approach
Authors: BÖNHOF GIDON J. , STROM ALEXANDER , RATHMANN WOLFGANG , HEIER MARGIT , MEISINGER CHRISTA , PETERS ANNETTE , RODEN MICHAEL , THORAND BARBARA , HERDER CHRISTIAN , ZIEGLER DAN
Published: June 2018

There is emerging evidence supporting a role of inflammation in the development and progression of diabetic sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes. We aimed to characterize inflammatory signatures associated with DSPN and/or type 2 diabetes using a multimarker approach. We measured 92 serum biomarkers including pro- and anti-inflammatory cytokines, chemokines, and growth factors (GF) using the Proseek Multiplex INF I assay (OLINK Proteomics) in 304 individuals with type 2 diabetes and polyneuropathy, defined by the Toronto Consensus Criteria (2011), from the PROPANE study (DSPN) as well as 158 individuals with type 2 diabetes without DSPN (T2D) and 354 individuals with normal glucose tolerance and without DSPN (CON) from the KORA F4 study (DSPN/T2D/CON [mean±SD]: age: 68±9/71±6/69±5 years; male: 76/59/41%; BMI: 30.8±5.3/30.8±4.4/26.9±3.7 kg/m²; diabetes duration: 13.5±9.6/7.6±5.8/- years; HbA1c: 7.4±1.3/6.6+1.0/5.5+0.3%). After adjustment for multiple testing and sex, age, BMI, and smoking, a biphasic pattern of serum levels (normalized protein expression values) with an increase in T2D and decrease in DSPN was observed for four GFs (e.g., transforming GF (TGF)-α: 4.51±0.51 vs. 4.63±0.56 vs. 3.91±0.51; vascular endothelial GF (VEGF): 10.9±0.5 vs. 11.0±0.5 vs. 10.8±0.6), two chemokines (e.g., C-C motif ligand 4 (CCL4): 8.18±0.57 vs. 8.4±0.6 vs. 7.93±0.68) and one cytokine (oncostatin M: 4.83±0.62 vs. 5.06±0.63 vs. 4.35±0.75). Compared to T2D, the levels of another 12 biomarkers were lower in DSPN (e.g., tumor necrosis factor (TNFSF)-14: 5.65±0.55 vs. 4.90±0.77; matrix metalloproteinase (MMP)-1: 14.4±0.7 vs. 14.1±0.9), while five were higher (e.g., CCL20: 5.2±1.1 vs. 5.79±1.23) (all P<0.00024).

In conclusion, deficits in growth factors promoting nerve regeneration/angiogenesis and a complex cross-talk between innate and adaptive immunity may contribute to the development of DSPN in type 2 diabetes.

Disclosure

G.J. Bönhof: None. A. Strom: None. W. Rathmann: Advisory Panel; Self; AstraZeneca. Research Support; Self; Novo Nordisk A/S. M. Heier: None. C. Meisinger: None. A. Peters: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. B. Thorand: None. C. Herder: Other Relationship; Self; Sanofi, Eli Lilly and Company. D. Ziegler: None.
Renal Function as a Predictor of Reamputation after Initial Transmetatarsal Amputation in the Perioperative Period—An ACS-NSQIP Study
Authors: AHN JUNHO , RASPOVIC KATHERINE M. , LALLI TRAPPER , LIU GEORGE T. , VANPELT MICHAEL D. , WUKICH DANE
Published: June 2018

Previous reports correlating renal function and reamputation after transmetatarsal amputation (TMA) have been mixed. This study aims to evaluate renal function as a factor for reamputation after initial TMA during the perioperative period in a large population database.

Patients who underwent TMA were identified in the American College of Surgeons-National Surgical Quality Improvement Program® database. Reamputation was defined as unplanned TMA or higher-level amputation in the 30-day perioperative period. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Of 1,775, the rate of reamputation was 6.5%. Reamputation was correlated with higher white blood cell counts (p<.00001), greater serum creatinine (p=.021), higher blood urea nitrogen (p=.021), type of glycemic control (p=.002), stage of CKD (p=.003), and dialysis (p=.001). CKD stage was directly associated with reamputation rates (p=.003) and mortality (p<.00001).

In the current study, CKD predicted reamputation after TMA and 30-day mortality. Our findings corroborate previous reports correlating dialysis-dependent renal failure and mortality. Whether patients in certain stages of CKD would achieve better outcomes with higher-level amputation rather than a TMA requires further study.

Disclosure

J. Ahn: None. K.M. Raspovic: None. T. Lalli: None. G.T. Liu: Consultant; Self; Gramercy Extremity Orthopedics. M.D. VanPelt: None. D. Wukich: None.
Critical Regulation of Angiogenesis by Nrf2 Signaling Is Absent in Diabetic Wound Healing
Authors: RABBANI PIUL S. , DAVID JOSHUA A. , SULTAN DARREN L. , VILLARREAL-PONCE ALVARO P. , KWONG JENNIFER , LEE JASMINE , SHEN CHEN , ABDOU SALMA A. , CERADINI DANIEL
Published: June 2018

Diabetes-associated ulcers account for 11% of non-traumatic limb and extremity amputations. Tailoring therapies for chronic diabetic wounds is challenging, however, as specific molecular/cellular events responsible for the extreme delays or lack of wound healing mostly remain at large. We previously identified dysfunction of the cytoprotective Nrf2/Keap1 signaling pathway induced by chronic hyperglycemia and diabetes. In the diabetic wound bed, we found detrimental impact on angiogenesis which is a requisite for tissue repair. Exogenous activation of Nrf2 in the whole diabetic wound bed accelerated healing and illustrated the promise of targeting Nrf2 activity for reversing diabetes-associated impairments. Here, we explored the specific role of Nrf2 in endothelial cells of the wound tissue repair niche, and corresponding deficiencies in Nrf2 activity during diabetic wound healing. We generated Cadherin5-CreER;Nrf2fl/fl mice to deplete Nrf2 specifically in endothelial cells, upon tamoxifen administration (Nrf2KO mice). Stented excisional wounds (10mm diameter) on Nrf2KO mice, induced prior to wounding, required 33±1.23 days for closure. This delayed repair phenotype was significantly higher than that of wild type wounds requiring 14.5±0.29 days (p<0.05), but very similar to the 31.5±0.65 days required by wounds on Leprdb/db diabetic mice. Successful inhibition of Nrf2 in microvasculature-derived endothelial cells in vitro demonstrated compromised proliferation (7.12±1.19 units), compared to cells transfected with non-sense siRNA (11.37±0.96 units, p<0.05). Endothelial cells with silenced Nrf2 also demonstrated less angiogenic capacity in vitro, unable to branch or form nodes. Our data prove that Nrf2 activity regulates endothelial cell proliferation and angiogenesis among features that are vital during wound repair. Our results reinforce the necessity of Nrf2 activation in skin for wound repair and underscore the impact of its deficiency in diabetic skin.

Disclosure

P.S. Rabbani: None. J.A. David: None. D.L. Sultan: None. A.P. Villarreal-Ponce: None. J. Kwong: None. J. Lee: None. C. Shen: None. S.A. Abdou: None. D. Ceradini: None.
Incidence and Risk Factors for Amputation in Patients with Diabetes in Japan—Historical Cohort Study Using a Nationwide Claims Database
Authors: KANEKO MASANORI , FUJIHARA KAZUYA , YAMAMOTO MASAHIKO , KITAZAWA MASARU , ISHIZAWA MASAHIRO , OSAWA TAEKO , HARADA MAYUKO , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , SONE HIROHITO
Published: June 2018

Since amputation of a lower extremity predisposes patients with diabetes to a lower quality of life and higher rates of cardiovascular events and mortality, identifying predictors of amputation is of clinical relevance in diabetes management. Although the incidence of amputation is known to be much lower in East Asians compared to those in Western countries, there has been no large cohort study of the accurate incidence of amputations in East Asians. Thus we analyzed data from a nationwide claims database involving 17,288 individuals with diabetes in Japan (2942 women, mean age 50.2 y, HbA1c 7.2%) from 2008-16. During a mean follow-up period of 5.3 y, 16 amputations occurred (0.17/1000 person-years), which was about one tenth of the typical rates reported by Western countries. Multivariate Cox regression analysis showed that age and HbA1c were independent predictors of amputation (hazard ratio (HR) 1.11(95% CI 1.03-1.19) and 1.43(1.13-1.81), respectively). Compared with those age <58 y and with HbA1c <8%, the HR for those age ≥58 y and HbA1c ≥8% was 32.0 (7.72-133.5). Kaplan-Meyer analysis confirmed the strikingly high risk in this category (Figure). Our results implied large differences in incidence and risk profiles for amputation in Japanese patients with diabetes, suggesting the need for ethnic group-specific strategies to prevent diabetic foot disease.

Disclosure

M. Kaneko: None. K. Fujihara: None. M. Yamamoto: None. M. Kitazawa: None. M. Ishizawa: None. T. Osawa: None. M. Harada: None. Y. Matsubayashi: None. T. Yamada: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
The Leucopatch® System in the Management of Hard-to-Heal Diabetic Foot Ulcers—A Multicentre, Multinational, Observer-Blinded, Randomised Controlled Trial
Authors: GAME FRANCES , JEFFCOATE WILLIAM , TARNOW LISE , JACOBSEN JUDITH L. , WHITHAM DIANE J. , HARRISON ELEANOR F. , ELLENDER SHARON J. , LONDAHL MAGNUS
Published: June 2018

Background: The LeucoPatch® device uses bedside centrifugation without additional reagents to generate a disc comprising autologous platelets, fibrin and leucocytes which is applied to the surface of the wound. The aim of the study was to test the effectiveness of LeucoPatch® on the healing of hard-to-heal foot ulcers in people with diabetes.

Methods: 595 people with diabetes and a foot ulcer consented to participate. After a 4 week run-in-period those with a reduction in ulcer area of < 50% were randomised to either pre-specified good standard care alone or care supplemented by weekly application of LeucoPatch®. The primary outcome was percentage of ulcers healed within 20 weeks, defined as complete epithelialisation confirmed by an observer blind to randomisation group and maintained for four weeks.

Results: 269 people were randomised; mean age 62 years, 82% male, 82% type 2 diabetes. In the intervention group 34.1% (n=45/132) of ulcers healed within 20 weeks vs. 21.6% (n=29/134) of the controls (OR 1.58, 95% CI 1.06-2.35; p= 0.02) by intention-to-treat analysis. Time to healing was shorter in the intervention group (p=0.0246) (Figure). No difference in adverse events was seen between groups.

Interpretation: The use of LeucoPatch® is associated with significant enhancement of healing of hard-to heal foot ulcers in people with diabetes.

Disclosure

F. Game: Research Support; Self; Reapplix aps. W. Jeffcoate: Research Support; Self; Reapplix Aps, Urgo, France. L. Tarnow: Stock/Shareholder; Self; Novo Nordisk A/S. J.L. Jacobsen: Consultant; Self; Reapplix. D.J. Whitham: Other Relationship; Self; Reapplix. E.F. Harrison: Research Support; Self; Reapplix. S.J. Ellender: None. M. Londahl: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; ReApplix AS.
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<0.008). DS and DW exhibited 2-fold and 2.5-fold decreases in epidermal Nrf2 staining, respectively, compared to NS and NW (p<0.001). Keap1-the cytoplasmic Nrf2 repressor-was overexpressed in DW when compared to NDW (p<0.04). DW showed a 75% reduction in nuclear Nrf2 protein expression (p<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<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 < .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<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 < .05). Patients’ perceptions of follow-up/care coordination, support for patient activation and self-management, and delivery design also improved over this period (ps < .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<0.01) (EX+HFD 29±5mg; EX+HFD/EX 32±2mg; p<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<0.01 vs. C], but exercise precondition restored it [EX+HFD-24±5% and EX+HFD/EX-32±8.9% dilatation; p<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<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<0.01 vs. C]. mRNA of the vasoprotective adipokine adiponectin was increased in PVAT of EX and EX+HFD/EX mice (p<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<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.
Interdisciplinary Educative Structured Diabetes Program Effect on Health-Related Quality of Life and Anxiety/Depression Perception in Patients Attending a Primary Care Diabetes Clinic in Mexico City
Authors: SILVA-TINOCO RUBÉN , CUATECONTZI ENEDINA TERESA , ALONSO AMAYRANI GÓMEZ , ROMERO-IBARGUENGOITIA MARIA ELENA , DE LA TORRE-SALDAÑ VIRIDIANA A. , CABRERA-GERARDO MARÍA DOLORES D. , GUZMÁN OLVERA EILEEN B. , GONZÁLEZ ENRIQUE , MEZA DANIELA G.
Published: June 2018

Quality of life(QoL) is an important health outcome and diabetes affects major components of QoL, including physical, psychological and social. There is limited evidence about the effect of Diabetes Self-Management Education (DSME) on QoL in primary care urban population of low- and middle-income countries. This study evaluated the effect on Health-Related Quality of Life (HRQoL) in patients who attended an interdisciplinary educative structured program at Clínica Especializada en el Manejo de la diabetes in México City-Iztapalapa in 2017. Intervention lasted 5 months and included individual and group sessions in a shared medical appointments model aimed at promoting self-care. In 252 patients with type 2 diabetes, HRQoL was assessed from the EuroQoL 5D-5L, which is a generic instrument for this purpose including 5 dimensions: mobility, self-care, daily activities, pain/discomfort, and anxiety/depression. It reports an indexed score and a visual analogue scale (VAS) score, and highest scores obtainable are of 1 and 100, respectively. Women represented 67%, and 59.6% had elementary or less education. Mean age was 55±10 years old, and mean duration of diabetes was 13±8 years. Indexed score and VAS score increased from 0.76±0.14 to 0.87±0.14 (mean variation 0.1±0.14; p=<0.001) and from 62.6±24 to 88.4±11 (mean variation 25.7±26; p=<0.001), respectively. The highest improvement in a HRQoL dimension was the decreased proportion of patients without problems perception related to anxiety/depression from 63.2% to 26% (p=<0.001). This non-pharmacological therapeutic approach focused on DSME improved HRQoL. Our findings suggest the role of DSME in this population beyond the traditional physical component impact, since it favors the fulfillment of multiple interrelated objectives through different mechanisms, generating a diversity of positive results, including HRQoL.

Disclosure

R. Silva-Tinoco: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. E. Cuatecontzi: None. A. Gómez Alonso: None. M. Romero-Ibarguengoitia: None. V.A. De La Torre-Saldañ: None. M.D. Cabrera-Gerardo: None. E.B. Guzmán Olvera: None. E. González: None. D.G. Meza: None.
Cost Calculation and Adherence to ADA Recommendations Based on a Flash Continuous Glucose Monitoring System for People with T1DM or T2DM Using MDI Therapy
Authors: HELLMUND RICHARD
Published: June 2018

Background: A novel, factory-calibrated, flash continuous glucose monitoring system (flash CGM; FreeStyle Libre™ system) was approved by FDA in September 2017. The clinical benefit of flash CGM as a replacement for routine self-monitoring of blood glucose (SMBG) for people using MDI therapy has been assessed in RCTs in T1DM (Bolinder, 2016) and T2DM (Haak,2017). In both 6-month studies, people using flash CGM achieved a substantial reduction in hypoglycemia compared with those using SMBG, without increasing HbA1c or reducing the dose of insulin. A cost calculation based on ADA recommendations is presented, comparing the acquisition cost of flash CGM with routine SMBG.

Methods: The ADA Standards of Medical Care in Diabetes (2017) recommend between 6 to 10 glucose tests per day for people with diabetes who are using MDI therapy. List prices are $1.42 per strip and $36.00 per sensor. Sensor duration is up to 10 days. In the T1DM RCT, people using flash CGM also used 0.5 SMBG tests/day on average; in the T2DM RCT, people using flash CGM also used 0.3 SMBG tests/day. The calculation is based on a 30-day month.

Results: Monthly cost of 10 SMBG/day is $426.00 and of 6 SMBG/day is $255.60. This is compared with the monthly sensor cost of $108.00, to which should be added the monthly cost of occasional SMBG based on utilization in the RCTs: $21.30 per person per month (PPPM) for people with T1DM and $12.78 for people with T2DM. For those testing 6 times/day, flash CGM saves over $120 PPPM compared with SMBG and it saves over $290 PPPM for people testing 10 times/day. For people testing more than 3 times/day, flash CGM has a lower acquisition cost than SMBG.

Conclusion: For people with T1DM or T2DM who use MDI therapy, flash CGM has demonstrated improved adherence to the ADA recommendation as well as reduced acquisition cost when compared with routine SMBG.

Disclosure

R. Hellmund: Employee; Self; Abbott. Stock/Shareholder; Self; Abbott.
Assessing the Evaluability of Type 2 Diabetes Prevention and Diabetes Management Interventions Focusing on Underserved Populations
Authors: FARRIS KIMBERLY D. , BONNER TIMETHIA , RUTLEDGE GIA E. , SMITH BRYCE
Published: June 2018

Rates of diabetes and diabetes-related health complications continue to rise among African American and Latino populations. Additional research and evaluations of the National Diabetes Prevention Program (National DPP) and diabetes self-management education and support (DSMES) programs are essential for identifying and disseminating best practices to help underserved populations prevent type 2 diabetes and manage diabetes. Authors implemented a systematic screening and assessment methodology to identify and examine National DPP and DSMES programs in underserved communities that demonstrated high participation rates and improved outcomes within African American and Latino populations. This study describes the screening methods used to identify programs and lessons learned from promising and innovative practices shown to be effective in recruitment and retention of African American and Latino populations into the National DPP and DSMES. Of the 9 National DPP and 9 DSMES programs that met the inclusion criteria, 4 of each were selected for evaluability assessments. Lessons learned regarding recruitment, retention, cultural tailoring, effectiveness of evidence, and organizational capacity were identified. Specific strategies that supported program success included community partnerships, instructor or coaches/participant racial concordance, holding classes in multiple locations, and including more group sessions. A panel of diabetes subject matter experts reviewed information on program design, implementation, and data collection capacity to recommend 4 programs to participate in a rigorous evaluation.

Disclosure

K.D. Farris: None. T. Bonner: None. G.E. Rutledge: None. B. Smith: None.
Aerobic Training Remodels Muscle Lipid Composition and Improves Intrinsic Mitochondrial Function in Men with Type 2 Diabetes
Authors: PINO MARIA F. , STEPHENS NATALIE , YI FANCHAO , HODGES ANDREW P. , PRATLEY RICHARD E. , SMITH STEVEN R. , GOODPASTER BRET H. , SPARKS LAUREN M.
Published: June 2018

The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with type 2 diabetes (T2D). We investigated the effects of exercise training on molecular signatures within SKM of T2D, employing integrated multi-omics data analyses including lipidomics [MS/MS-shotgun], global DNA methylation and transcriptomics [RNA-Seq]. Muscle tissue and cellular mitochondrial respiration was quantified by high resolution respirometry. Ten weeks of aerobic training increased monolysocardiolipin (MLCL), a marker of mitochondrial remodeling, reduced total and specific species of sphingomyelin (SM), phosphatidylserine (PS) and ceramides lipid content and improved intrinsic mitochondrial respiration in SKM of T2D without alterations in mitochondrial DNA copy number or cardiolipin content. Exercise training differentially modified 50 DNA methylation sites. Among these genes, NOX4, acts as an oxygen sensor and catalyzes the reduction of reactive oxygen species (ROS), and PLCE1, catalyzes the hydrolysis of phosphoinositol 1,4,5-triphosphate (IP3) and DAG, were hypo-methylated and hyper-methylated, respectively, following training. Exercise training differentially regulated 70 transcripts in SKM of T2D that resulted in enrichments of lipid and amino acid metabolism and β-oxidation pathways.

In summary, aerobic training improves intrinsic and cell autonomous SKM mitochondrial function and modifies SKM lipid composition in men with T2D, with potentially advantageous augmentations of oxidative stress and insulin signaling pathways.

Disclosure

M.F. Pino: None. N. Stephens: None. F. Yi: None. A.P. Hodges: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc.. S.R. Smith: None. B.H. Goodpaster: None. L.M. Sparks: None.
Factors Associated with Medication Adherence among Type 2 Diabetes Mellitus Patients in Nepal
Authors: SHAKYA PUSHPANJALI , KARMACHARYA BIRAJ M. , SHRESTHA ARCHANA , KULSENG BAARD E.
Published: June 2018

Background: Diabetes is increasing globally resulting in 1.5 million deaths in 2012. The high mortality is due to life-threatening complications of uncontrolled sugar. Medication helps to control glucose level and prevents its complications.

Objective: To identify the factors associated with medication adherence among type 2 diabetes mellitus (DM) patients.

Methods: A hospital based cross sectional study was conducted among 343 patients visiting Dhulikhel Hospital, Nepal for their regular Fasting Blood Sugar test from September to December 2016. Inclusion criteria were (i) type 2 DM patients (ii) under diabetes medication from at least past three months (iii) aged 18 years or above. We measured medication adherence using Nepali version of 8 item Morisky Medication Adherence Scale (MMAS-8) (© 2007 Donald E. Morisky). Adherence was categorized as high if MMAS score was equal to 8 and moderate/low if it was less than 8. We used standard questionnaire to measure socio-demographic and clinical factors. Multivariate logistic regression was applied to assess factors associated with medication adherence.

Results: Proportion of high and moderate/low medication adherence among the respondents were 60.9% and 39.1% respectively. In multivariate logistic regression, high medication adherence was found to be positively associated with formal education [AOR: 2.43 (95% CI: 1.34, 4.39), p=0.003] and attendance of diabetes counseling [AOR: 1.76 (95% CI: 1.02, 3.04), p=0.04] after adjusting for age, occupation, annual household per-capita income, medicine intake duration and diabetes medicine types. Other variables in the model were not statistically significantly associated.

Conclusion: Formal education and attendance of diabetes counseling were found to positively affect patients’ adherence to medicine. We encourage heath care institutions to provide counseling services to all type 2 DM patients and focus more on those who are least educated.

Disclosure

P. Shakya: None. B.M. Karmacharya: None. A. Shrestha: None. B.E. Kulseng: None.
MicroRNA Regulated Transcriptomic Changes during Aging in Human Skeletal Muscle Are Reversible with Exercise Training
Authors: VALENTINE JOE , GHOSH SANGEETA , MILHOLLAND BRANDON , GELFOND JONATHAN A. , MUSI NICOLAS
Published: June 2018

Muscle mass declines with age (sarcopenia) in both men and women resulting in impaired physical function and altered glucose metabolism. Endurance exercise training can mitigate and even reverse some of the changes in skeletal muscle structure and function, which are observed at advanced age. To gain insight into the potential mechanisms driving sarcopenia and the adaptive response to training, we conducted deep sequencing on vastus lateralis muscle obtained from healthy, younger (n=14; age=27±0.89 y; 8 women, 6 men) and older (n=14, age=71±1.39 y; 7 women, 7 men) subjects before and after a 4 month endurance training program. We analyzed the sequencing data with bioinformatics tools to determine whether miRNAs that change with age can be reverted back to youthful levels with training. We found that skeletal muscle from women had 7 miRNAs and men had 8 miRNAs that changed with age and were reverted back to youthful levels with training, respectively. In older trained females these 7 miRNAs targeted 94 unique transcripts in the top 1000 differentially expressed genes between post-training compared to pre-training and these transcripts were involved in lipid metabolism, glycolysis, and growth. In older men the 8 miRNAs with youthful signatures after training had 146 unique targets involved in phosphoprotein and PI3K-AKT signaling, as well as cholinergic synapses. Notably, miR-29b-3p was primarily responsible for the regulation of target transcripts within the PI3K-AKT pathway in older trained men; similar family members (miR-29a-3p and miR-29c-3p) have been directly linked to insulin sensitivity in preclinical models. All miRNAs with youthful signatures in older trained subjects had opposing expression patterns to their target mRNAs. We conclude that some of the aging related changes to the skeletal muscle transcriptome are under the regulation of miRNAs and that exercise training can reverse these changes.

Disclosure

J. Valentine: None. S. Ghosh: None. B. Milholland: None. J.A. Gelfond: None. N. Musi: None.