bluuebunny/crossref_metadata_2025_split huggingface dataset:
597-P: Prolonged Therapeutic Effects of Photoactivated Adipose-Derived Stem Cells following Diabetic Ischemic Injury
Authors: FAN XIN , WU JIANBO 
Published: June 2020

Aim: Adipose-derived stem cells (ADSCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.
Methods: Cultured ADSCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Photoactivated and non-light-treated ADSCs were injected into the tail vein of mice fed a high-fat diet (HFD), following which unilateral hindlimb ischemia was induced. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse-transcription polymerase chain reaction, Flow cytometry was used to determine the characterization of ADSCs and endothelial progenitor cell (EPC). Human ADSCs secretomes were analyzed by liquid chromatography tandem mass spectrometry.
Results: Our study demonstrated that photoactivated ND-ADSCs prolonged functional blood flow perfusion and increased ADSCs-derived EPC and neovascularization thirty-eight days after ligation, when compared with saline-treated controls. Profiling analysis in ischemic muscles showed upregulation of genes associated with pro-angiogenic factors after injection of photoactivated ND-ADSCs when compared with the non-light-treated ADSCs or saline treated HFD mice. Mass spectrometry revealed that light-treated ADSCs conditioned medium retained a more complete pro-angiogenic activity with significant upregulation of angiogenesis related proteins.
Conclusion: Our data demonstrates that photoactivated ND-ADSCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.

Disclosure
X. Fan: None. J. Wu: Research Support; Self; HarmonyRegena Inc.
598-P: Risk Factors of Amputation In Patients with Diabetic Charcot Foot In Taiwan
Authors: TSENG YU-HSIANG , CHEN LEE-WEI 
Published: June 2020

Charcot foot is a rare and severe complication of DM neuropathy. Patients with diabetic Charcot foot could progress to chronic ulcer or amputation in severe condition. However, there were few studies addressing the risk factors of amputation in Charcot foot. This study aimed to compare the risks of chronic ulcer or amputation in diabetic Charcot foot. A total of 25 patients with Charcot foot were enrolled from 2010 to 2019 in Kaohsiung Veterans General Hospital. We analyzed the correlation between underlying diseases with chronic ulcer or amputation. The average of our patients was 55±13.3 years old with 34.4±31.1 months following up. In patients below 50 years old with obesity (BMI&gt;24), higher prevalence of Charcot foot was noted compared with those with BMI&lt;24 (p&lt;0.05). The Charcot foot patients have a 7-times higher risk of amputation compared with patients with chronic ulcer (p&lt;0.05), 2.6-times higher risk compared with patients with peripheral arterial occlusion diseases (p&lt;0.05), and 5-times higher risk with patients with osteomyelitis (p&lt;0.05). A Higher risk of amputation was also noted in Charcot foot patients with more than 2 times debridement (OR:5.05, p&lt;0.05). A higher prevalence of osteomyelitis was noted in patients of Charcot foot with chronic ulcer than those without chronic ulcer (p&lt;0.05). Patients with diabetic Charcot foot have a higher risk of amputation compared with patients with chronic ulcer or peripheral arterial occlusion diseases. Osteomyelitis should be aware in chronic ulcer patients with Charcot foot. It’s important to control the ulceration and infection progression in this group of patients. Overweight is an important risk factor for Charcot foot in young patients.

Disclosure
Y. Tseng: None. L. Chen: None.
60-OR: OGTT Glucose Response Curves (GRC), Insulin Sensitivity (IS), and ß-Cell Function (ßCF) in RISE: Youth–Adult Contrast at Randomization and in Response to Interventions to Preserve ßCF
Authors: ARSLANIAN SILVA A. , GHORMLI LAURE EL , KIM JOON YOUNG , HANNON TAMARA S. , MATHER KIEREN J. , CAPRIO SONIA , BARENGOLTS ELENA , NADEAU KRISTEN J. , UTZSCHNEIDER KRISTINA , KAHN STEVEN E. ,   THE RISE CONSORTIUM
Published: June 2020

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p&lt;0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p &lt;0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p&lt;0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults.
In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape.

Disclosure
S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None.

Funding
American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases
601-P: A Meta-analysis of Clinical Effectiveness of Amnion Tissue Products in the Management of Diabetic Foot Ulcers
Authors: PARKS VIRGINIA E. , BANKS JAMINELLI , JOHNSON LANCE , LIETTE MICHAEL D. , CRISOLOGO PETER , LAVERY LAWRENCE A. 
Published: June 2020

Background: Diabetic foot ulcers are complex and create a heavy financial burden to the health system. The purpose of this systematic review and meta-analysis is to assess the clinical effectiveness and safety of human amniotic membrane tissue products in diabetic foot ulcerations.
Methods: A meta-analysis was performed to evaluate the clinical effectiveness of the use of amnion tissue products verses the standard of care in the management of diabetic foot ulcers. A literature search of PubMed/Medline, Cochrane Library, and ClinicalTrials.gov for articles published before December 30, 2019 was performed to identify randomized controlled clinical trials that included human subjects with diabetic foot ulcers treated with amnion tissue products.
Results: The literature search revealed ten randomized clinical trials that fit the selection criteria to be included in the meta analysis. Analysis of the percent of wounds healed yielded the following results: 4 weeks (treatment group 64.2%, SOC 18.8%), 6 weeks (treatment group 60.9%, SOC 60.7%), 12 weeks (treatment group 70.8%, SOC 32.4%) with P &lt;0.01. There was no significant difference in mean number of adverse events between groups with a p=0.71.
Conclusions: The results of this meta-analysis of the available evidence suggest that the application of amniotic tissue products in diabetic foot ulcerations significantly increases the percent of diabetic foot ulcers healed as compared to stand of care alone.

Disclosure
V.E. Parks: None. J. Banks: None. L. Johnson: None. M.D. Liette: None. P. Crisologo: None. L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew.
602-P: The Use of Thermography for Studying Diabetic Foot Complication through the Alteration of Thermoregulation Mechanism
Authors: SERANTONI VINCENT , JOURDAN FRANCK , LOUCHE HERVE , SULTAN ARIANE 
Published: June 2020

The aim of the present study was to characterize thermoregulatory mechanism in the feet depending on the lower limb diabetes complication (i.e., diabetic foot neuropathy, peripheral arterial disease or both) using a thermal camera.
A transversal study was conducted to analyse the effect of diabetes complication on thermoregulation mechanism. This study was approved by the Hospital of Lapeyronie (Montpellier, France, clinical trials NCT03872089). 51 participants were enrolled, among these participants 8 were subjects without diabetes and 43 were subjects with diabetes mellitus. Among them, 10 were diagnosed with a peripheral neuropathy (PN), 4 with a peripheral arterial disease (PAD), 8 with both complication (PN-PAD) and 23 without these specific complication (DM).
Enrolled participants were placed barefoot in a semi-Fowler’s position in a room at 25°C controlled temperature during 5 min, enabling thermal acclimation. A first 10 min thermal recording of both plantar foot sole was done, acting as baseline, then they were asked to perform the 6-min walking test. It was assumed that thermoregulation activation would occur during exercise or during the hyperaemia phase (post-exercise). Finally, subjects were then recorded for a further 10 min, just after the exercise period. In each case, foot skin temperature oscillations were under interest.
Evaluation of results before the 6-minute walk exercise revealed poorer difference, it seems crucial to activate thermoregulation mechanism before any interpretation.
Finally, we found that it was possible to distinguish the presence of PN, or PAD, among diabetic subjects. It seems also possible to scale the severity of the complication.
In conclusion, alteration of thermoregulatory mechanism amplitude is associated with presence of PN or PAD. Thermal camera may give valuable information to the practitioner, allowing the latter one of having accurate information about the complication, linked to the DF, for each patient.

Disclosure
V. Serantoni: None. F. Jourdan: None. H. Louche: None. A. Sultan: None.

Funding
LabEx NUMEV (2011-LABX-076)
604-P: Deficiency of Dedicator of Cytokinesis 5 Impairs Epidermal Wound Healing
Authors: ZHENG YI , QU HUA 
Published: June 2020

Wound healing is impaired under diabetes, and the proliferative phase of healing, mainly the charge of epidermal keratinocytes, is essential for tissue repair. Failure to maintain this process contributes to the dysfunction of tissue homeostasis and global burden; however, the factors that mediate this process are not fully understood. Here, we identified dedicator of cytokinesis 5 (Dock5) as a critical regulator of cutaneous wound healing. Specifically, Dock5 is highly upregulated during the proliferative phase of wound repair and is predominantly expressed in epidermal keratinocytes. It regulates keratinocyte migration and proliferation and influences the functions of angiogenesis and extracellular matrix (ECM) deposition by binding with integrin α3 (Itgα3). Genetic ablation of Dock5 in mice leads to attenuated re-epithelialization and granulation tissue formation, while Itgα3 overexpression improves the repressive effects on skin repair seen in Dock5 KO mice. Moreover, in patients and animal models of diabetes, Dock5 expression at the skin edge is reduced, further suggesting a direct correlation between its abundance and healing capability. Rescuing Dock5 expression in diabetic mice causes a significant improvement in re-epithelialization, angiogenesis, collagen deposit, ECM production and granulation. Our study provides a potential therapeutic target for wound healing impairment during diabetes.

Disclosure
Y. Zheng: None. H. Qu: None.

Funding
Army Medical University (2017R013, 2019XQYYYJ003-2)
605-P: Endothelial-Specific Overexpression of Metallothionein Prevents Diabetes Mellitus–Induced Impairment in Ischemia Angiogenesis via Preservation of HIF-1a/SDF-1/VEGF Signaling in Endothelial Progenitor Cells
Authors: WANG KAI , DAI XIAOZHEN , CHEN JING , SHEN FEIXIA , WINTERGERST KUPPER A. , EPSTEIN PAUL N. , CAI LU , TAN YI 
Published: June 2020

Diabetes-induced oxidative stress contributes to endothelial progenitor cells (EPCs) dysfunction and impairs endothelial regeneration. Thus, we tested whether increasing antioxidant protein metallothionein (MT) in EPCs promotes angiogenesis in a hind limb ischemia (HLI) model in endothelial-specific MT transgenic (JTMT) mice with high fat diet and streptozocin (HFD/STZ)-induced diabetes. Compared with littermate wild type (WT) diabetic mice, JTMT mice had improved blood flow recovery and angiogenesis after HLI. Similarly, transplantation of JTMT bone marrow-derived mononuclear cells (BM-MNCs) stimulated greater blood flow recovery in db/db mice with HLI than did WT BM-MNCs. The improved recovery was associated with augmented EPC function: mobilization and infiltration in JTMT mice; and, enhanced capillary EPC incorporation in db/db mice. Further, cultured JTMT-EPCs had enhanced cell survival, migration, and capillary tube formation in hypoxia/hyperglycemic conditions compared with WT-EPCs. Mechanistically, MT overexpression enhanced hypoxia-inducible factor 1α (HIF-1α), stromal cell-derived factor (SDF-1) and vascular endothelial growth factor (VEGF) expression, and reduced oxidative stress in ischemic tissues. MT’s pro-EPC effects were abrogated by siRNA knockdown of HIF-1α without affecting MT’s anti-oxidant action. These results indicate that endothelial-specific MT overexpression is sufficient to protect against diabetes-induced impairment of angiogenesis by promoting EPC functions though upregulation of HIF-1α/SDF-1/VEGF signaling and reducing oxidative stress.

Disclosure
K. Wang: None. X. Dai: None. J. Chen: None. F. Shen: None. K.A. Wintergerst: None. P.N. Epstein: None. L. Cai: None. Y. Tan: None.

Funding
American Diabetes Association (1-11-BS-017, 1-15-BS-018 to L.C.)
61-OR: Genetic and Metabolic Determinants of the Incretin Effect in Obese Adolescent with Prediabetes
Authors: GALDERISI ALFONSO , SAMUELS STEPHANIE , PIERPONT BRIDGET , MAN CHIARA DALLA , SANTORO NICOLA , CAPRIO SONIA 
Published: June 2020

Prediabetes and type 2 diabetes in obese youths are associated with a reduced incretin effect. Herein, we investigated the metabolic and genetic determinants of incretin effect in obese youths with normal and impaired glucose tolerance. We studied 35 obese youth (15.8±2.4y, BMI 39.9±6.1kg/m2, NGT/IGT 18/17, F/M 18/17). All participants were genotyped for the TCF7L2 rs7903146 variant and underwent: A) 180-minutes OGTT and a matched iso-glycemic intravenous glucose tolerance test (iso-IVGTT) to estimate the incretin effect, by modelling of C-peptide secretion (SR), and insulin sensitivity (SI) by the oral minimal model; B) a hyperglycemic clamp with arginine stimulation to estimate insulin secretion independently from the oral phase. Incretin effect was measured as (SROGTT-SRiso-IVGTT)/SROGTT. Insulin clearance (CL) was computed as SROGTT-[Vx insulin]/AUCInsulin-OGTT. Determinants of the Incretin effect were assessed by multivariate logistic regression.Insulin clearance (p=0.004), T allele for TCF7L2 (p=0.018) and 2-h glucose (p=0.035) were independent determinants of the incretin effect (Figure A), with an increase in insulin clearance associated with greater incretin effect (Figure B). Lower insulin clearance, higher 2-h glucose and the risk-genotype of TCF7L2 rs7903146 are associated with a lower incretin effect in obese adolescents with prediabetes.

Disclosure
A. Galderisi: None. S. Samuels: None. B. Pierpont: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. N. Santoro: None. S. Caprio: None.

Funding
National Institutes of Health (R01DK111038); Patterson Foundation
610-P: Health System Barriers for Rural Patients with Diabetic Foot Ulcers
Authors: BRENNAN MEGHAN , SUTHERLAND BRYN , PECANAC KRISTEN , BARTELS CHRISTIE M. 
Published: June 2020

Background: Rural patients with diabetic foot ulcers (DFUs) face a 40% increased risk of major amputation. We aimed to identify health system barriers contributing to this disparity.
Methods: We interviewed 44 participants involved in the care of rural patients with DFUs: 6 rural PCPs, 12 rural specialists, 12 urban specialists, 9 support staff, and 5 patients/caregivers. Directed content analysis of transcripts was guided by a conceptual model describing how PCPs and specialists co-manage patients. We adapted the model to describe how rural patients receive care for DFUs.
Results: When caring for rural patients with DFUs, collaboration between rural PCPs and rural specialists was strong. However, collaboration broke down when urban specialists were needed. Urban referrals were hindered by 1) time-consuming processes, 2) negative provider interactions, and 3) multiple, disconnected electronic health records (Fig). Time needed to finesse referrals detracted from rural clinicians’ focus on medical care. Urban specialists struggled to triage referrals due to incomplete data. Subsequent communication between rural and urban providers was also suboptimal.
Conclusion: Poor collaboration across rural and urban health systems was described as the main health system barrier driving the rural disparity in major amputations. Fostering collaboration between rural and urban providers may reduce the rural disparity in major amputations.

Disclosure
M. Brennan: None. B. Sutherland: None. K. Pecanac: None.

Funding
University of Wisconsin Institute for Clinical and Translational Research (WPP3086)
614-P: Receiving Diabetes Self-Management Education Associated with Following Self-Care and Clinical Preventive Care Practices
Authors: LUNDEEN ELIZABETH A. , MENDEZ ISABEL , SAUNDERS MAGON M. , SAADDINE JINAN B. 
Published: June 2020

Background: Diabetes self-management education and support services empower people with diabetes to follow preventive care practices that reduce disease complications.
Objective: We describe self-reported receipt of diabetes education among people with diabetes, and its association with following recommended self-care and clinical preventive care practices.
Methods: We analyzed data from the 2017 Behavioral Risk Factor Surveillance System for 42,631 adults (≥18 years) with self-reported diabetes (all types) in 38 states, D.C., and Guam. Diabetes education was defined as ever taking a diabetes self-management class. We assessed four self-care practices (daily glucose testing, daily foot checks, smoking abstention, and regular physical activity), and six clinical practices (pneumococcal vaccination, biannual HbA1c test, and an annual dilated eye exam, influenza vaccination, healthcare visit for diabetes, and foot exam). We used multivariable logit regression with predicted margins to predict the probability of following these practices, by diabetes education, controlling for sociodemographic factors.
Results: Of adults with diabetes, 52.3% reported receiving diabetes education; those who did had a higher (p&lt;0.01) predicted probability for 3 of 4 self-care practices [daily glucose testing (70.1% vs. 51.2%, respectively), daily foot check (62.6% vs. 52.2%), and regular physical activity (65.6% vs. 56.9%)] and all 6 clinical practices [pneumonia vaccination (72.8% vs. 59.1%), biannual HbA1c test (81.5% vs. 70.4%), and an annual eye exam (74.3% vs. 65.7%), flu vaccination (60.0% vs. 54.2%), healthcare visit (92.3% vs. 86.2%), and medical foot exam (83.0% vs. 68.5%)].
Conclusions: Diabetes education was positively associated with following preventive care practices. Developing strategies to improve receipt of education can be informed by studies that elucidate barriers to education.

Disclosure
E.A. Lundeen: None. I. Mendez: None. M.M. Saunders: None. J.B. Saaddine: None.
615-P: Engaging Family Supporters Improved Patient Activation among Adults with T2DM: An RCT
Authors: ROSLAND ANN-MARIE , PIETTE JOHN , TRIVEDI RANAK B. , LEE AARON A. , STOLL SHELLEY C. , MOR MARIA K. , OBROSKY D. SCOTT , KERR EVE A. , HEISLER MICHELE 
Published: June 2020

We evaluated the effectiveness of an intervention for patient-family dyads aimed at improving diabetes self-management and outcomes for adults with T2DM (AWD) at risk for complications. AWD were randomized with a family supporter to an intervention vs. usual care for 12 months. The intervention provided dyads: one health coaching session, biweekly automated phone calls to prompt action plans on new diabetes health concerns, coaching calls to prepare for medical visits, and medical visit summaries. 239 AWD-supporter dyads were enrolled at two Veterans Health Administration sites. AWD eligibility criteria included baseline HbA1c&gt;8% or systolic blood pressure (SBP)&gt;150mmHg. Intention-to-treat analyses of changes in outcomes were adjusted for baseline outcome levels, patient-supporter cohabitation, and patients’ baseline insulin use. 96% of dyads had complete 12-month outcome data. Enrolled patients were on average 60±9 years old and had HbA1c levels of 8.5±1.6% and SBP 140mmHg (IQR 128,150). 70% lived with their supporter. Over 12 months, Patient Activation Measure scores (pre-specified primary outcome) increased significantly more in the intervention group (intervention effect +2.6 points (95%CI 0.005, 5.149). There were no statistically significant differences by arm in diabetes-specific cardiac risk score, HbA1c, or SBP change. Patient self-reported adherence to healthy eating increased significantly more in the intervention group (intervention effect +0.7 days/week (95% CI 0.2, 1.2) but not for other self-management behaviors. 97% of patients and 94% of supporters in the intervention group agreed they would recommend the program to others. This family supporter-patient dyadic intervention successfully increased patient activation and one health behavior but not physiologic outcomes over a 12 month period. Improving sustained engagement of family supporters in care of diabetes for adults is feasible and could serve as an additional source of support for diabetes care.

Disclosure
A. Rosland: None. J. Piette: None. R.B. Trivedi: None. A.A. Lee: None. S.C. Stoll: None. M.K. Mor: None. D. Obrosky: None. E.A. Kerr: Advisory Panel; Self; Bind Insurance. M. Heisler: None.

Funding
Health Services Research and Development (IIR 14–074-1); Michigan Center for Diabetes Translational Research (5P60-DK09292); Michigan Claude D. Pepper Older Americans Independence Center (AG-024824); VA Ann Arbor Center for Clinical Management Research