bluuebunny/crossref_metadata_2025_split huggingface dataset:
491-P: Corneal Nerve Sensitivity—Early Detection of Diabetic Peripheral Neuropathy (DPN)
Authors: YOREK MARK A. , CORREIA MARCELO , KARDON RANDY , POOLMAN PIETER 
Published: June 2023

Introduction: Density of sub-epithelial corneal nerves have been promoted as a surrogate marker for early diagnosis of DPN. As an alternative, we developed an objective functional test of corneal sensitivity (Invest Ophthalmol Vis Sci. 2016, 57: 2412-9). In this study we provide verification of this methodology in human subjects with DPN.
Methods: Following verification of DPN, response to a drop of isotonic vs. 5% NaCl (hypertonic) solution was recorded (primary endpoint). Ratio of time that the eyelids were closed from 10s to 60s following application of each solution were quantified using an image analysis program.
Results: We examined 24 subjects with type 2 diabetes and 12 age-matched controls. The presence of DPN in diabetes vs. control subjects was verified by completing the Michigan Neuropathy Screening Instrument questionnaire and lower extremity examination including amplitude and conduction velocity of the sural nerve. The presence of eye discomfort was examined for each subject by completing the DEQ5 and Ocular Surface Disease Index (OSDI) questionnaires. DPN was confirmed in all subjects with diabetes as well as presence of mild to moderate ocular surface disease. Two control subjects had mild ocular surface disease but no peripheral neuropathy. Cochet-Bonnet filament esthesiometer examination revealed significant corneal sensitivity impairment in subjects with diabetes vs. control subjects (5.64 ± 0.08 vs. 5.97 ± 0.03 cm, respectively). Corneas of subjects with diabetes were also significantly less sensitive vs. controls to application of hypertonic solution (0.18 ± 0.01 vs. 0.29 ± 0.04, respectively). Data is presented as mean ± S.E.M. There was no difference in sensitivity to the isotonic solution.
Conclusion: Corneal nerves that penetrate the epithelium and sprout near the surface of the eye and are the first to exhibit the "dying-back" phenomenon associated with DPN. Clinical evaluation of the sensitivity of these nerves could be a valuable method for early detection of DPN.

Disclosure
M.A.Yorek: Consultant; Novo Nordisk. M.Correia: Research Support; Eli Lilly and Company, Novartis, Novo Nordisk. R.Kardon: None. P.Poolman: Stock/Shareholder; FaceX LLC.

Funding
U.S. Department of Veterans Affairs (RX000889)
498-P: Prevalence and Impact on Quality of Life of Diabetic Retinopathy in African Americans with End-Stage Kidney Disease on Hemodialysis
Authors: ZABALA ZOHYRA E. , MOAZZAMI BOBAK , EGEOLU MICHELLE , CALEON RAMONCITO L. , GERGES AMANY Y.G. , GALINDO RODOLFO J. , MCCOY ROZALINA G. , PENG LIMIN , UMPIERREZ GUILLERMO 
Published: June 2023

Background: The prevalence, severity, and quality of life (QoL) impact of diabetic retinopathy (DR) among African Americans (AA) with end-stage-kidney disease (ESKD) receiving dialysis are unknown.
Methods: We conducted a prospective cross-sectional study in 93 AA adults with type 1 (n=9) and type 2 (n=84) diabetes with ESKD on hemodialysis. The diagnosis of DR was based on a review of medical records and/or having a positive photograph with a portable hand-held device (Optomed Aurora retinal camera) reviewed by both artificial intelligence software (AEYE Health’s retinal screening system) and a retinal specialist. Visual acuity was assessed with the Snellen Chart. Associations with QoL (ascertained using kidney disease QoL and depression questionnaires), physical disability (ascertained using visual impairment questionnaire), and social determinants of health (SDoH) including personal and household income, marital status, health insurance, education, food insecurity, or employment status assessed by standardized questionnaires.
Results: The overall prevalence of DR was 75%, with 33% of patients having mild, 9.6% moderate and 57.4% severe DR. A total of 43% had normal visual acuity, 45% had moderate and 12% severe visual impairment. We found high burden of disease, multiple SDoH challenges, and low QoL among all patients, with most unemployed or disabled, living below poverty line, mainly receiving public health insurance, reporting poor general health, and substantial time spent dealing with kidney disease interfered with daily and family activities. However, the presence of DR had no significant impact on physical health and QoL compared to subjects without DR.
Conclusion: DR is present in 75% of AA patients with diabetes and ESKD on hemodialysis. ESKD has a significant burden on general health and QoL; however, DR has a minor additional impact on the overall physical health and QoL in people with ESKD and diabetes.

Disclosure
Z.E.Zabala: None. B.Moazzami: None. M.Egeolu: None. R.L.Caleon: None. A.Y.G.Gerges: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. R.G.Mccoy: Consultant; Emmi. L.Peng: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.
500-P: Causal Effect of SGLT2 Inhibition on Diabetes-Related Retinopathy (DR) and Macular Edema (DME)
Authors: STEVENS HENRY , BREEN JAMES M. , COOPER BLAKE A. 
Published: June 2023

Background: SGLT2 inhibitors have been shown to slow cardiac and renal disease progression. Currently, there is limited literature on the impact of SGLT2 inhibitors on DR and more specifically DME. Objective: Evaluate the effect of SGLT2 inhibitors on central subfoveal thickness (CST) in patients with T2D and on the need and frequency of intravitreal injections (IVI) for DME.
Methods: A retrospective matched cohort study with propensity score matching to reduce confounding and determine treatment effect.
Covariates: age, sex, type of DM, last A1c, level of retinopathy, insurance, IVI, Visual Acuity (VA).
Treatment: SGLT2i use. Primary Outcome: CST on Optical Coherence Tomography (OCT).
Secondary Outcomes: IVI use and frequency for DME. By ICD-10 codes 10,026 patients were found to have diabetes and were seen in 2021 at Retina Associates, LLC Kansas City. Retrospectively screened 1,000 consecutive patient medical records from this cohort and included those with T2D and on an SGLT2i. We excluded those with incomplete records, T1D, and those who had a second diagnosis that could cause macular edema. Results: 321 patients had DR; 280 with T2D of which 71 were on an SGLT2i and included for analysis. Baseline cohort characteristics: mean age (SD): 62.2 yr (11.4); 58.9% were male; 76.1% White, 11.1% Black, 6.8% Hispanic/Latino; 13.2% used tobacco; 75.4% had HTN; last recorded A1C 7.6 (1.6); Visual Acuity in ETDRS letters OD: 74.1 (12.9) OS: 73.8 (14.7); CST OD: 279.9 (56.6) OS: 279.6 (54.7). Comparing CST and the need for IVI to those not on an SGLT2i the CST OD/OS was 280.1 (32)/280.3 (36.3) vs 279.9 (62.8)/279.4 (59.7) and 40.8% vs 36.8% required IVI with a risk ratio of 1.13 and a risk difference of 0.03 and p-value of 0.55 95% CI [-0.07, 0.14]. After Propensity Score Matching: ATE risk difference was 0.04 and a p-value of 0.37 and 95% CI [-0.05, 0.14].
Conclusions: No positive or negative effect on mean CST or difference in the average treatment effect for DME was found for those taking an SGLT2 inhibitor.

Disclosure
H.Stevens: None. J.M.Breen: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.
506-P: Regulation of ANGPTL3 by SEL1L-HRD1 ER-Associated Degradation
Authors: ZHOU LINYAO , LIN LIANGGUANG , SUN SHENGYI , QI LING 
Published: June 2023

Angiopoietin-like 3 (ANGPTL3) is a liver-derived circulating factor critical for systemic lipid metabolism via the inhibition of lipoprotein lipase (LPL). Loss-of-function mutations in ANGPTL3 in humans and mice reduce circulating levels of triglycerides. Here, we report the discovery of a novel mechanism regulating the biosynthesis and maturation of nascent ANGPTL3 in the endoplasmic reticulum (ER). Mice with acute or chronic liver-specific deletion of SEL1L-HRD1, the most conserved branch of mammalian endoplasmic reticulum (ER)-associated degradation (ERAD) machinery, exhibit significantly lower levels of triglyceride and cholesterol in the serum with reduced weights of both epididymal and inguinal white adipose tissues (WAT). Various proteomics screenings have identified ANGPTL3 as a possible link between SEL1L-HRD1 ERAD and hypolipidemia. Indeed, ANGPTL3 is a bona fide endogenous substrate of SEL1L-HRD1 ERAD in the liver and in the absence of ERAD, ANGPTL3 protein is retained in the ER, forming high-molecular weight aggregates. This abnormal ER retention of ANGPTL3 accounts for a reduced circulating level of ANGPTL3, therefore contributing to hypolipidemia in ERAD-deficient mice. Together, this study not only uncovers a novel regulator for ANGPTL3 and novel targets in the treatment of hyperlipidemia in obesity and diabetes.

Disclosure
L.Zhou: None. L.Lin: None. S.Sun: None. L.Qi: None.
51-LB: Race Specific Effects of a Carbohydrate-Restricted Diet on Acute and Maximal C Peptide Response to Glucose in Adults with Type 2 Diabetes
Authors: GOWER BARBARA , GOSS AMY M. , TIMOTHY GARVEY W. 
Published: June 2023

Beta-cell response to glucose is compromised in individuals with type 2 diabetes (T2D), possibly due to lipid infiltration of the pancreas from excessive carbohydrate consumption. This study was conducted to determine if a eucaloric carbohydrate restricted diet (~9% energy from carbohydrate, 65% energy from fat), compared to a eucaloric fat restricted diet (~55% energy from carbohydrate, 20%energy from fat), would improve beta-cell response to glucose in participants with T2D. Participants were 43 African American and European American adults with T2D not using insulin. Medications were discontinued 1-2 weeks (depending upon the medication) prior to baseline testing. A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide responses to glucose at baseline and after 12 weeks of controlled diet therapy (all food provided). Based on the detection of a race-by-diet interaction (P=0.06), data were analyzed within each race group. At 12 weeks, a significant effect of diet was observed by ANCOVA on acute C-peptide response in African Americans (2-fold greater with the carbohydrate restricted diet, P&lt;0.05), and on maximal C-peptide response in European Americans (50% greater with the carbohydrate restricted diet, P&lt;0.01), after adjusting for change in body weight. Paired t-test revealed an improvement in acute C-peptide response within African Americans on the carbohydrate restricted diet (P&lt;0.01) from baseline to week 12, and an improvement in maximal C-peptide response within European Americans on the carbohydrate restricted diet (P&lt;0.01). No changes in beta-cell function were observed in response to the fat restricted diet. These results suggest that a carbohydrate restricted diet has beneficial effects on beta-cell function that are race-specific and independent of weight loss.

Disclosure
B. Gower: Consultant; Abbott. A. M. Goss: Advisory Panel; Novo Nordisk, Consultant; Weight Watchers International. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens.

Funding
National Institutes of Health (R01DK116726)
514-P: A 13-Year Retrospective Analysis of an Admission-Avoidance Strategy Using Intramuscular Antibiotics in Treating “Borderline-Severe“ Diabetic Foot Infections
Authors: DHATARIYA KETAN , GOODAY CATHERINE , FUNG ADRIEL H. 
Published: June 2023

Aim: To determine the outcomes of using intramuscular (IM) antibiotics as an admittance avoidance strategy in people presenting with a ‘borderline-severe’ diabetic foot infection.
Methods: Methods:122 patients (accounting for 141 episodes) were treated for ‘borderline-severe infection’ between January 2009 and April 2022. Prior to the introduction of this service they would have required an acute hospital admission. Individuals were followed up to determine whether the use of intramuscular antibiotics had prevented acute hospital admission.
Results: Our clinic saw, on average, 420 contacts per month during the study period. Approximately 5 people per week were admitted directly from specialist clinics or the emergency department with a severe infection. Of those seen in the specialist foot clinic, only 1 person per month was deemed appropriate to receive IM treatment. These had a mean age (±SD) of 61 years (13.3), and 83% were male, and 25% had type 1 diabetes. The mean (IQR) number of injections was 5.5 (6.0). Of these, 39/141 subsequently needed hospital admission. The remaining 102 people were successfully treated as outpatients, with 95 ulcers healing. Of the 39 admissions, 20 needed IV antibiotics alone, 14 had a minor amputation, 5 had a major amputation.
Conclusions: Admission avoidance strategies are increasing important in reducing the pressure on hospitals beds. Like others, our hospital increasingly uses outpatient intravenous antibiotic services, but that has its own pressures. We now successfully use either IV or IM administration to treat borderline-severe diabetic foot infections depending on the capacity of either service, thus avoiding acute hospital admission which leads to significant cost savings.

Disclosure
K.Dhatariya: Other Relationship; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. C.Gooday: Speaker's Bureau; AstraZeneca. A.H.Fung: None.
515-P: Study to Evaluate the Relationship between Inpatient Glycemic Control as Measured by CGM and Wound Healing in Patients Admitted for Diabetic Foot Ulcer (DFU)
Authors: ROGERS KAITLYN K. , RASHIED AMMAR A. , SCHECHTER MARCOS , FAYFMAN MAYA 
Published: June 2023

We performed a post-hoc analysis of hospitalized patients admitted with DFU enrolled in an inpatient continuous glucose monitor (CGM) study. Bivariate analysis was conducted between those with wound healing vs. non-healing over a 16-week period. Logistic regression was performed to assess the following CGM metrics and likelihood of wound healing: TIR (70-180 mg/dl), TAR (&gt;180 mg/dl) and TBR (&lt;70 mg/dl). Potential confounders included in the multivariate analysis were age, race and sex, history of peripheral arterial disease, renal failure, prior amputation, and ulcer duration. Results of patient characteristics are summarized in the Table. Of 230 patients enrolled in our CGM studies, 62 (27%) were admitted for DFU. Sixteen weeks after discharge, 9 (15%) patients were lost to follow-up, 13 (21%) had healed, and 39 (62%) had not healed. Of the non-healed, 10 (15%) had an amputation, 3 (4.7%) died, and 26 (41%) had a persistent ulcer. We did not find an association between the likelihood of healing and CGM derived glycemic metrics: fully adjusted models for TIR (OR 0.99, 95% CI 0.96-1.02), TAR (1.01 95% CI 0.98-1.04), and TBR (0.85; 95% CI 0.52-1.40). While glycemic control remains an important predictor of diabetes complications, we did not find an association between glycemic control in the hospital based on CGM metric and post-discharge healing.

Disclosure
K.K.Rogers: None. A.A.Rashied: None. M.Schechter: None. M.Fayfman: None.

Funding
Dexcom, Inc.
517-P: Machine Learning Algorithms Using Electronic Medical Record and Ultrasonography of Lower Extremities for 10-Year Risk Assessment of Diabetic Foot Ulcer in China
Authors: WU LIN , LIANG YUNAN , HE XUEMIN , CHEN YANMING 
Published: June 2023

Objective: Accurate prediction of diabetic foot ulcer (DFU) occurrence in patients with type 2 diabetes mellitus (T2DM) is crucial for determining appropriate treatment strategy and avoiding amputation and infection. Here, we explored machine learning algorithms (ML) of electronic medical record (EMR) for predicting the incident of DFU.
Methods: In this retrospective longitudinal observational cohort, 26579 cases from T2DM database of The Third Affiliated Hospital of Sun Yatsen University from Jan 2011 to Dec 2019 were screened and finally 2770 patients without DFU were enrolled. During 5.6 years of follow-up, 178 patients occurred DFU. 44 clinical parameters including EMR and imaging finding were used to develop a DFU risk prediction model using XGBoost, RF, and LR.
Results: ML models were established in 178 patients with DFU (110 male, mean 61.1±12.4 years), and 2591 patients without DFU (1424 male, mean 59.0±12.1 years). XGBoost model achieved the best performance in predicting DFU occurrence with an AUC of 0.94, which is better than the performance of RF with AUC of 0.91and LR with AUC of 0.89. A DFU incident significantly increased in high-risk patients (&gt;10%) in the next 10 years.
Conclusion: Our study provided a simple and effective risk tool for the prediction of 10-year DFU risk, which can help professionals clinical screening and decision-making for T2DM patients.

Disclosure
L.Wu: None. Y.Liang: None. X.He: None. Y.Chen: None.
519-P: Randomized Clinical Trial to Compare Cryopreserved and Lyopreserved Placental Cord Tissue to Treat Complex Diabetic Foot Surgical Wounds—A Proof of Concept Study
Authors: LAVERY LAWRENCE A. , KILLEEN AMANDA L. , SULUDERE MEHMET A. , CRISOLOGO PETER 
Published: June 2023

Objective: To compare the incidence of infection, healing and time to heal in patients treated with cryopreserved (CPAT) and lyopreserved amniotic tissue (LPAT) in complex diabetic surgical wound (CDFW).
Methods: This single-blinded 12-week randomized clinical trial compared cryopreserved and lyopreserved amniotic cord tissue to treat complex diabetic foot wounds (CDFW). LPAT or CRAT was applied at baseline and again after four weeks. We enrolled subjects with UT2A-D and 3A-D wounds (depth to tendon, muscle, or bone with infection and/or PAD) and excluded subjects with ABI&lt;0.5 or TBI&lt;0.3, untreated osteomyelitis, and autoimmune diseases. We used a 3-D camera to evaluate wound area and volume. The Chi-squared test was used to compare clinical outcomes and the Wilcoxon Ranked Sum Test to compare wound area and volume.
Results: The mean baseline wound areas were 12.9cm2 ±10.7 for CPAT and 11.7cm2 ±7.0 for LPAT. The mean baseline wound volume were 7.5cm3 ±8.1 for CPAT and 9.2cm3±10.2 for LPAT. There was no difference between CPAT and LPAT in healing (36.8% vs. 19.0%, p=0.21) and infection (10.5% vs. 9.5%, p=0.72). There was no difference in mean wound area reduction between CPAT and LPAT (75.9± 32.3% vs. 65.5±38.4%, p=0.41), nor in mean volume reduction (85.0±30.8% vs. 79.9±31.9%, p=0.61). When we stratified wound dimensions, there was no difference between CPAT and LPAT in subjects that had 90-99% wound volume reduction (36.8% vs. 47.6%), 70-89% wound volume reduction (15.8% vs 19.0%) and 0-69% wound volume reduction (10.5% vs. 19.0%). There was no difference between CPAT and LPAT in subjects that had 90-99% wound area reduction 90-99% (10.5% vs. 23.8%), 70-89% (26.3% vs. 19.0%) and 0-69% (26.3% vs. 38.1%).
Conclusion: Cryopreserved and Lyopreserved amniotic tissue provided similar results in patients with complex diabetic foot wounds.

Disclosure
L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew. A.L.Killeen: Research Support; 3M/KCI, AstraZeneca, BioTissue surgical, Hologenix, LLC, Integra LifeSciences, Kent Imaging Inc., Microbion, PolarityTE, Inc., Smith+Nephew, Stark Enterprises, LLC, Xyken, VasoActiv, ViOptix. M.A.Suludere: None. P.Crisologo: None.

Funding
Smith & Nephew
526-P: Increasing the Confidence of Health Care Professionals Treating Patients Living with Type 1 Diabetes through the Support-Pro Online Education Platform
Authors: KATZ ALEXANDRA , RABASA-LHORET RÉMI , TALBO MERYEM K. , HOUSNI ASMAA , HILL LEE , ROY-FLEMING AMÉLIE , HAAG SARAH , BRAZEAU ANNE-SOPHIE 
Published: June 2023

Introduction: Support-Pro is a comprehensive online platform that was developed for healthcare professionals (HCP) and covers all technological, treatment and lifestyle needs for type 1 diabetes (T1D) management in short, practical modules. It was developed as studies have demonstrated that HCPs who work in healthcare not specific to T1D, find it difficult to keep up-to-date with new developments that could improve T1D care and management. However, specialized online resources, such as Support-Pro, could help rectify this problem. The objective of the study is to assess whether Support-Pro can increase HCPs confidence in treating and supporting people with T1D (PWT1D) and their satisfaction with the platform.
Methods: Open-label, non-randomized, 3-month trial with 142 HCPs who had access to Support-Pro, and 66 who completed 3 months on the platform (NCT04859205).
Results: On average, the 66 participants (years of practice: 14±10; 90% women; 71% Caucasian; 44% dietitians, 30% nurses, 23% pharmacists, 3% physician or resident physician) reported at 3 months, an average 10% improvement in their confidence (total score 58% to 68%; p&lt;0.0001) and a median satisfaction score of 76%. HCPs most valued features that supported knowledge gain, such as downloadable PDF documents (72%) and case studies (44%). The platform was most used in first month of access (page views 1st month: 50 [5;135] vs. 3rd month: 0 [0;18]).
Conclusions: HCPs who completed 3 months on Support-Pro platform reported increased confidence in treating PWT1D and high appreciation of learning content and modalities. This platform could improve the support and advice provided to PWT1D followed-up outside specialized clinics.

Disclosure
A.Katz: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. M.K.Talbo: None. A.Housni: None. L.Hill: None. A.Roy-fleming: None. S.Haag: Other Relationship; Omnipod. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé.

Funding
Strategy Patient-Oriented Research (JT1-157204); JDRF (4-SRA-2018-651-Q-R)