bluuebunny/crossref_metadata_2025_split huggingface dataset:
422-P: Intrinsic Brain Connectivity in Chronic Painful Diabetic Neuropathy: A Resting-State fMRI Study
Authors: TEH KEVIN , WILKINSON IAIN D. , SHILLO PALLAI RAPPAI , SLOAN GORDON P. , TESFAYE SOLOMON , SELVARAJAH DINESH 
Published: June 2021

Painful diabetic neuropathy (DN) is a common, distressing complication of diabetes that is discordant with the degree of peripheral nerve pathology. Very little is known about the cerebral processes involved in pain processing in painful DN. Here we investigated resting-state brain connectivity associated with prolonged pain in DN.
Methods: 58 subjects and 36 matched controls were compared with regard to both behavioural measures of pain perception and resting-resting state functional Magnetic Resonance Imaging. The resting-state fMRI brain connectivity was investigated using 20 seed regions located in cardinal pain processing brain regions. Resting-state fMRI analysis was performed using the NITRC Functional Connectivity (CONN) Toolbox and SPM8 (welcome Trust Centre for Neuroimaging London, UK) in Matlab 2014a (the MathWorks, Natick, MA, USA). Functional connectivity matrices between the pre-specified seeds were calculated and the HV versus painful DN phenotype interaction examined.
Results: Relative to controls, painful DPN patients displayed increased brain connectivity predominately for the supplementary motor areas (p&lt;0.01) and the primary sensorimotor cortex (p&lt;0.001). Similar results were found when painful DPN subjects were compared with those with No DPN. Conversely, we observed an increase in brain connectivity between the primary somatosensory cortex and cingulate cortex (p&lt;0.01), prefrontal cortex (p&lt;0.01) and amygdala (p&lt;0.01) between painful and painless DPN patients.
Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in painful DPN patients.

Disclosure
K. Teh: None. I. D. Wilkinson: None. P. Shillo: None. G. P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc. D. Selvarajah: None.

Funding
Health Education England/University of Sheffield Knowledge Exchange Fund; National Institute for Health Research; EME
43-LB: Evaluating Health Status in the PRONTO-Pump-2 Study
Authors: PACZKOWSKI ROSIRENE , PIRAS DE OLIVEIRA CAROLINA , CHO JANG IK , GOLDYN ANDREA , POON JIAT LING , HANKOSKY EMILY R. , IGNAUT DEBRA A. 
Published: June 2021

Background: In PRONTO-Pump-2, a Phase 3, 16-week, randomized, double-blind clinical trial in patients with type 1 diabetes on continuous subcutaneous insulin infusion, ultra rapid lispro (URLi) showed superior postprandial glucose control and noninferior HbA1c reduction, with less hypoglycemia compared to Humalog® (Lispro). Although primarily reported as mild in severity, incidence of infusion site reactions was higher with URLi compared to Humalog (37.7% vs. 10.1%). We assessed patient-reported health status in the PRONTO-Pump-2 trial as an exploratory measure.
Methods: The EQ-5D-5L (which includes a visual analogue scale rating perceived health [VAS; 0-100 from worst to best imaginable health state]) was administered at baseline and endpoint (week 16 or early discontinuation) to patients on URLi (N=215) or Humalog (N=217). The EQ-5D-5L assesses 5 dimensions of health status (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which a health state index score ranging from less than 0 (worse than death) to 1 (perfect health) is calculated. Change from baseline to endpoint (last observation carried forward) in scores was analyzed using an ANCOVA model.
Results: At endpoint, mean health state index scores showed no significant differences between treatments (URLi, 0.88 [standard error 0.009]; Humalog, 0.89 [0.009]) with an increase from baseline of +0.01 (0.009) within each treatment. On the dimension of pain/discomfort, distribution of responses was similar between treatments. Endpoint VAS scores were also similar between URLi and Humalog (80.2 [0.82] and 80.8 [0.78], respectively) but decreased from baseline within each treatment: URLi, -1.1 (0.82); Humalog -0.5 (0.78).
Conclusion: In PRONTO-Pump-2, the EQ-5D-5L indicated no differences in health status, including the pain/discomfort dimension, between patients on URLi versus Humalog, despite more frequent reports of infusion site reactions with URLi treatment.

Disclosure
R. Paczkowski: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Amgen Inc., Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Amgen Inc. C. Piras de oliveira: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. J. Cho: None. A. Goldyn: Employee; Self; Eli Lilly and Company. J. Poon: Employee; Self; Eli Lilly and Company. E. R. Hankosky: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. D. A. Ignaut: Employee; Self; Eli Lilly and Company.

Funding
Eli Lilly and Company
43-OR: Islet Autophagic Flux Is Impaired Prior to the Onset of Type 1 Diabetes
Authors: CLARK AMY L. , YAN ZIHAN , REMEDI MARIA S. , DIWAN ABHINAV 
Published: June 2021

Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic beta cells. Early events within the islet leading to T1D include increased beta cell ER and oxidative stress and increased inflammatory cytokines. Autophagy is a cellular pathway activated by cell stressors which leads to decreased cellular levels of ER stress and oxidative stress, and inactivates inflammatory pathways. While there is a good amount of data suggesting impaired autophagy in type 2 diabetes, relatively little is known about changes in autophagy during the development of T1D. In the following study we characterized changes in the autophagy pathway during development of T1D using NOD mice. We compared gene expression and autophagic flux in islets from female NOD mice prior to the onset of diabetes at 4, 8,10, and 12 weeks of age. At 10 weeks of age the inflammatory cytokines IL1-B and IL-6 and the ER stress marker CHOP were markedly elevated in NOD islets. In addition, at 10 weeks of age, TFEB expression was also significantly elevated in islets; indicating activation of the autophagy pathway. We then evaluated autophagic flux in NOD islets by measuring LC3-II accumulation in the presence or absence of chloroquine, an inhibitor of autophagosome to lysosomal fusion. LC3-II accumulation after CQ exposure was significantly lower in islets starting at 8 weeks of age, demonstrating an impairment in autophagic flux which precedes the development of islet ER stress and diabetes. This study demonstrates activation of the autophagy pathway when islets are expressing high ER and inflammatory stress markers during the development of T1D. However, despite activation, autophagic flux is reduced. Impairments in the autophagy pathway may worsen beta cell ER, oxidative and inflammatory stress, ultimately leading to cell death and hastening the progression to diabetes. These data suggest that therapies targeting restoration of autophagy should be evaluated as interventions to delay or prevent T1D.

Disclosure
A. L. Clark: None. Z. Yan: None. M. S. Remedi: None. A. Diwan: None.

Funding
Washington University Diabetes Research Center (P30DK020579 to A.L.C.); National Institutes of Health (R01DK123163, R56DK098584 to M.S.R.)
447-P: The Efficacy and Safety Trial of ENERGI-F703 in Diabetic Wound Healing: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Trial
Authors: YOUNG GUANG-HUAR , LIN JIUN-TSAI , CHENG YI-FANG , CHEN HAN-MIN , HUANG CHUN-FANG 
Published: June 2021

Diabetic foot ulcers (DFUs) is a catastrophic ailment that exerts serious medical and psychological impact on diabetic patients. ENERGI-F703 is a hydrogel containing 0.02% adenine as a prodrug for the replenishment of cellular ATP levels to accelerate diabetic wound healing. To demonstrate its efficacy and safety in patients with DFU, 141 patients with type 2 diabetes (T2D) ≥ 20 years old with HbA1c 6.5-12 % and intractable DFUs (Wagner grade 1-3 without active osteomyelitis) were enrolled, randomized 2:1 ENERGI-F703 group (67.4%) to vehicle group (32.6%) for 12 weeks. Most target ulcers were grade 2 (63.6%, N=84) and located mainly on the foot sole (30.3%, N=40) or toe (27.3%, N=36). The primary endpoint was complete ulcer closure rate at the end of treatment. Secondary endpoints included the time required to complete ulcer closure, the accumulated confirmed ulcer closure rate and percentage change in ulcer size at each of the post-treatment visit, and adverse event incidence. Patients with confirmed complete ulcer closure were follow-up for additional 12 weeks and patients with incomplete ulcer closure were additional 4 weeks. An intend-to-treat (ITT) population of 132 subjects and a per-protocol (PP) population of 107 were included in efficacy analyses. Among the PP population with Wagner grade 1 or 2 target ulcers, we observed a significantly higher response rate in the ENERGI-F703 group compared to the vehicle group (48.0% vs. 20.8%, P = 0.0250). Among the ITT population, we also observed a higher response rate in the ENERGI-F703 group compared to the vehicle group (40.3% vs. 20.7%, P = 0.0656). Time to complete target ulcer closure was also faster among patients receiving ENERGI-F703 Gel in both the ITT population (P = 0.0380) and PP population (P = 0.0180). There were no suspected unexpected serious adverse reactions observed throughout the study. Our study showed that ENERGI-F703 Gel is an effective and well-tolerated treatment for DFU.

Disclosure
G. Young: Employee; Self; Energenesis Biomedical Co., Ltd. J. Lin: Employee; Self; Energenesis Biomedical Co., Ltd. Y. Cheng: Employee; Self; Energenesis Biomedical Co., Ltd. H. Chen: None. C. Huang: Employee; Self; Energenesis Biomedical Co., Ltd.
454-P: Pharmacist-Led Diabetes Self-Management Education and Reduction of Readmission Rates at a County Hospital
Authors: MULALA LISELI , LENHOFF TAMARA 
Published: June 2021

Pharmacist-led Diabetes Self-Management Education and Reduction of Readmission Rates at a County Hospital With 10.5% of the US population or 34.2 million people affected by diabetes, education is greatly needed. The American Diabetes Association (ADA) and the Association for Diabetes Care and Education Specialists (ADCES) state that Diabetes Self-Management Education or Training (DSME/T) improves diabetes management, which can avoid hospital admissions and readmissions. Although DSME/T has traditionally been provided by nurses and dieticians, pharmacists can play a part, given their expertise in medication management, non-pharmacological therapies, and monitoring. The ADA and ADCES recommend that people with diabetes receive DSME/T at diagnosis, annually, when factors influence self-management, and at transitions of care. Therefore, a pharmacist-led transitions of care program was developed to reduce readmissions for patients with diabetes at Zuckerberg San Francisco General Hospital and Trauma Center. This hospital serves a diverse, low-income, and unhoused patient population, increasing the challenges of diabetes management. Pharmacists and pharmacy trainees were given a refresher course on DSME/T. Low-health literacy handouts in several languages, as well as demonstration kits, glucometers, insulin and insulin supplies, were all utilized for patient education. The objective of the study was to determine whether using pharmacists as educators, could reduce hospital readmissions. In 2017, provision of DSME/T at this institution was less than 5% and increased to 74% by December 2019, with the implementation of this program. The rate of readmission for patients with diabetes who received DSME/T was 11.7% compared to 19.2% for those who did not; an absolute risk reduction in readmission of 7.5%. Pharmacists and pharmacy trainees should use DMSE/T to help reduce readmissions, improve outcomes, and increase the national levels of patients with diabetes receiving DSME/T.

Disclosure
L. Mulala: None. T. Lenhoff: None.
459-P: An Examination of Introductory Sessions Offered by CDC-Recognized National Diabetes Prevention Program Lifestyle Change Programs
Authors: WILLIAMS PAMELA , ELKINS WENDI , PROIA KRISTA , TAYEBALI ZOHRA , AXELROD KATHLEN , ESQUIVEL NIKIE S. , SMITH AKIMI , PORTERFIELD DEBORAH 
Published: June 2021

The Centers for Disease Control and Prevention (CDC)’s National Diabetes Prevention Program (National DPP) lifestyle change program (LCP) is effective in preventing or delaying type 2 diabetes among people with prediabetes. Increasing enrollment in the National DPP LCP remains a priority. Some LCPs attempt to increase enrollment by offering introductory sessions, pre-enrollment sessions that aim to recruit, engage, and enroll participants based on emerging evidence linking introductory sessions with increased enrollment. As part of a national survey of CDC-recognized organizations offering the National DPP LCP, we examined the content and characteristics of introductory sessions currently offered. Of the 544 organizations who reported offering introductory sessions, the majority provide essential information by overviewing the organization’s LCP (98%) and providing information about type 2 diabetes prevention (79%) during the session. Most provide social support by offering an opportunity to meet the coach (86%) and for program staff and participants to mingle (69%), but only 36% offer light refreshments. Most assess eligibility and readiness to change by offering participants an opportunity to take a risk test to determine eligibility (74%), assess their readiness to join (63%), and to enroll in the program, if interested (71%). Only 34% provide resources for participants not eligible for the program. Session characteristics intended to overcome behavioral barriers to enrollment as identified in prior studies are less common: 39% conduct activities to help participants feel that they can be successful, 38% include testimonials from successful program participants, and 26% assess how soon a participant plans to enroll. There is room for improvement in incorporating behavioral science principles in introductory sessions. Future work will examine associations between specific introductory session characteristics and enrollment.

Disclosure
P. Williams: None. W. Elkins: None. K. Proia: None. Z. Tayebali: None. K. Axelrod: None. N. S. Esquivel: None. A. Smith: None. D. Porterfield: None.
473-P: Feasibility and Acceptability of a Direct-to-Home Diabetes Self-Management Education and Support Telemedicine Program (DSMES) with High-Risk Patients in a Rural, Underserved Area
Authors: KRALL JODI S. , NG JASON , JOHNSON PATRICIA A. , REYNOLDS SHARI L. , SIMINERIO LINDA M. 
Published: June 2021

Ongoing support is critical to DSMES effectiveness, but difficult to realize, particularly in underserved areas with limited resources. The purpose of this study, initiated February 2020, was to evaluate the feasibility and acceptability of Telemedicine for Reach, Education, Access, Treatment, and Ongoing Support (TREAT-ON), a DSMES model delivered primarily through direct-to-home videoconferencing.
Methods: High risk patients with diabetes (A1c &gt;9% or unplanned care) from rural federally qualified health centers were referred to TREAT-ON. Participants completed an initial face-to-face or virtual visit with a Diabetes Care and Education Specialist (DCES) to assess needs and develop self-management treatment plan and behavioral goals. Planned follow-up visits, used to support achieving and sustaining goals and outcomes, were conducted through videoconferencing. To assess feasibility and acceptability over first 3-months of participation, visit frequency, duration, completion rates, and technology issues were tracked and patients completed the Telehealth Usability Questionnaire (TUQ).
Results: Participants (n=25) were 60% female, 92% White, mean age 47.6±13.6y, mean A1c 11.5±1.8% and 76% had Medicare or Medicaid. They participated in 3 video visits, on average, lasting a mean of 35 minutes/visit. Of all scheduled video visits (n=99), 71% were successfully completed and 23% had technology issues (difficulty setting up system, connectivity issues). The TUQ revealed that participants were highly satisfied with the TREAT-ON videoconferencing approach (4.7/5), finding it useful (4.5/5), easy to learn/use (4.5/5), reliable (4.3/5), with quality interface (4.6/5) and interaction (4.7/5).
Conclusion: This telehealth DSMES model offers a promising approach to improve opportunities for ongoing support to vulnerable individuals in underserved communities.

Disclosure
J. S. Krall: Research Support; Self; Becton, Dickinson and Company, Sanofi. J. Ng: Research Support; Self; Sanofi-Aventis. P. A. Johnson: None. S. L. Reynolds: None. L. M. Siminerio: Advisory Panel; Self; Abbott Diabetes, Bayer U. S., Research Support; Self; Becton, Dickinson and Company.

Funding
National Institute of Diabetes And Digestive and Kidney Diseases (R34DK123370)
478-P: Effect of Nonpharmacological Management of Chronic Constipation in Diabetic Patients
Authors: NISHIMORI EITA , NAKA MOTOJI 
Published: June 2021

Background: Chronic constipation is highly prevalent in diabetic patients. The treatment of chronic constipation in general patients is mainly lifestyle modification and pharmacological therapy. The efficacy of non-pharmacological treatment, i.e., behavioral therapy to improve lifestyle and defecation habits, for chronic constipation in diabetic patients is not well known. This study aimed to determine the efficacy of non-pharmacological management for chronic constipation in diabetic patients.
Methods: We conducted a questionnaire on defecation for diabetic patients aged 20 to 75 years at Asama General Hospital outpatient clinic. Patients diagnosed with chronic constipation according to Rome IV criteria were randomly assigned to two groups. The intervention group instructed behavior therapy to improve constipation. Specifically, we provided guidance on defecation behavior, exercise, water and dietary fiber intake, and guidance on a defecation diary recording daily defecation status. The other group received usual medical care as a control group. The questionnaire was conducted again at the next outpatient clinic.
Results: Eighty of 545 diabetic patients (14.7%) had chronic constipation. The average age of constipated patients was 59.3 years, frequency of defecation 3.7 times/week, stool form (Bristol Stool Form Scale) 2.8, straining during defecations 78,8% and sensation of incomplete evacuation of defecations 42.5%. After the intervention, there was a significant increase in the frequency of defecation (4.8 vs. 3.9 times/week, P=0.008) and improvement in constipation symptoms (P=0.018) in the intervention group compared to the control group. In addition, stool form and straining during defecations were significantly improved before and after comparison within the intervention group (P &lt;0.05).
Conclusion: Our findings suggest that non-pharmacological management, including behavioral therapy for chronic constipation in diabetic patients, was effective.

Disclosure
E. Nishimori: None. M. Naka: None.
50-OR: Validation of Fear of Hypoglycemia Screener: Results from the T1D Exchange Registry
Authors: LIU JINGWEN , POON JIAT LING , BISPHAM JEOFFREY , PEREZ-NIEVES MAGALY , HUGHES ALLYSON , CHAPMAN KATHERINE S.M. , MITCHELL BETH , SNOEK FRANK J. , FISHER LAWRENCE 
Published: June 2021

Objective: To examine reliability and validity of a newly developed fear of hypoglycemia (FoH) screener as a practical and actionable tool for in-clinic use in adults with type 1 diabetes (T1D), in accordance with ADA’s position on psychosocial care.
Methods: In this validation study, adults with T1D were recruited from the T1D Exchange Registry to complete a draft screener online; potential items were previously identified from literature review, and interviews with health care professionals (HCPs) and people with T1D. Standard psychometric analyses assessed reliability and validity of the screener. The final FoH screener comprised 9 items assessing 2 domains - “worry” (6 items) and “behavior” (3 items).
Results: The final sample comprised 592 adults with T1D (age 43.1 ± 15.3 years; duration of T1D 24.1 ± 15 years, 66.7% females, 91.6% White, 5.2% Hispanic, self-reported HbA1c 7.1% ± 1.2%). Approximately 30% of participants reported severe hypoglycemia in the past 12 months; 33.4% reported impaired awareness of hypoglycemia. The FoH screener showed internal consistency (Cronbach’s α=0.88) and was highly correlated (r=0.71-0.75) with the Hypoglycemia Fear Survey (“worry” and “behavior” subscales and total scores), confirming reliability. Construct validity of the FoH screener was demonstrated with significant correlations with depression (r=0.44), anxiety (r=0.47), Diabetes Distress Subscales (powerlessness, management distress, hypoglycemia distress) (r=0.49-0.66); These correlations are considered moderate. Additionally, multivariable regression analysis showed that higher FoH screener scores were significantly associated with higher HbA1c (regression coefficient, β=0.04) and multi-morbidities (β=0.03).
Conclusions: This 9-item FoH screener demonstrated good reliability and validity. Further research is planned to assess clinical usability to help appropriately identify patients and assist effective HCP-patient conversations around FoH.

Disclosure
J. Liu: None. J. Poon: Employee; Self; Eli Lilly and Company. J. Bispham: None. M. Perez-nieves: Employee; Self; Eli Lilly and Company. A. Hughes: None. K. S. M. Chapman: None. B. Mitchell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. F. J. Snoek: Advisory Panel; Self; Abbott Diabetes, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Novo Nordisk, Sanofi. L. Fisher: Consultant; Self; Ascensia Diabetes Care, Lilly Diabetes, Speaker’s Bureau; Self; Dexcom, Inc.

Funding
Eli Lilly and Company