bluuebunny/crossref_metadata_2025 huggingface dataset:
576-P: Association between Carbohydrate Antigen 125 and Diabetic Retinopathy in People with Type 2 Diabetes
Authors: YANG GUANGRAN
Published: June 2020

Objective: Carbohydrate antigen 125 was reported to be related with incident type 2 diabetes risk and coronary artery calcification. However, little was known about its role in diabetic retinopathy. This study was to analyze the relationship between carbohydrate antigen 125 and diabetic retinopathy in type 2 diabetes.

Method: Type 2 diabetes people hospitalized in the department of Endocrinology without a history of tumor from March 2018 to February 2019 were enrolled. Diabetic retinopathy was diagnosed on the results of fundus photography. Serum carbohydrate antigen 125 was measured. People with cataract, other retina diseases, neoplastic diseases, cancers, hepatic failure and renal failure were excluded.

Results: All the people were divided into two groups based on the results of fundus photography. There were 177 people with diabetic retinopathy and 291 people without diabetic retinopathy. There was no significant difference in age, body mass index, fasting glucose, and lipid profiles between the diabetic retinopathy group and nondiabetic retinopathy group (p>0.05). There was significantly different in gender, duration of diabetes, hypertension, HbA1c, and urinary albumin excretion rate (p<0.05). Diabetic retinopathy people had higher carbohydrate antigen 125 compared to people without diabetic retinopathy (9.75±6.14U/ml, 8.11±4.04U/ml, respectively, p<0.05). Logistic analysis showed that carbohydrate antigen 125 was associated with diabetic retinopathy after adjusting gender, duration of diabetes, HbA1c, hypertension, triglyceride, urinary albumin excretion rate and other confounding variables (adjusted OR=1.059, p<0.05).

Conclusions: In this study, diabetic retinopathy had higher carbohydrate antigen 125 compared with people without diabetic retinopathy. Carbohydrate antigen 125 might be associated with diabetic retinopathy in type 2 diabetes. Further large-scale studies are needed to confirm this association.

Disclosure

G. Yang: None.

Funding

National Natural Science Foundation of China (81471009); Beijing Health System, Health and Technical Personnel of High Level Plan (2014-3-013); Capital’s Funds for Health Improvement and Research (2016-2-2054, 2020-026285-000005)
578-P: A Loss-of-Function Mutation of NRG4 Contributes to the Pathogenesis of NAFLD and Insulin Resistance
Authors: HU CHENG , LI YANGYANG
Published: June 2020

Neuregulin 4 (Nrg4), as an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication which elicits beneficial metabolic effects in NAFLD. We identified a mutation of NRG4 by whole exome sequencing in 151 severe obese subjects and exome array in a community-based population of 2388 subjects. Nrg4 R44H mutation carriers have increased visceral fat area, abnormal liver function and hyperlipidemia. Then we hypothesized that the mutation would affect the function of Nrg4 and accelerated the development of NAFLD. Compared with Nrg4 WT mice, Nrg4 R44H mice gained more weight, accompanied by significantly increased fat mass and lipid accumulation in the liver upon HFD feeding. In vitro, we found that Nrg4 WT activated ErbB4 and stimulated the STAT5 signaling pathway and decreased transcriptional activation of srebp1c. As we hypothesized, the primary hepatocytes treated with Nrg4 R44H purified protein didn’t showed the same activation of cell signaling as Nrg4 WT. In order to reveal the potential mechanisms of loss-of-function of Nrg4 R44H, we performed surface plasmon resonance (SPR) experiments to test the binding affinity of purified Nrg4 and ErbB4 proteins. The SPR results showed Nrg4 WT bind to ErbB4 with an affinity of 2.20uM, while Nrg4 R44H showed no binding. Taken together, these results suggested Nrg4 WT prevented HFD-induced NAFLD and alleviated insulin resistance, and demonstrated Nrg4 R44H lost its ability to bind to the receptor ErbB4, thus losing its physiological function.

Disclosure

C. Hu: None. Y. Li: None.
579-P: Dyslipidemia in Type 2 Diabetic Mice Is Improved by Targeting Smad3 with a Smad3 Inhibitor SIS3
Authors: HE HUIJUN , HUANG XR , MA RONALD C. , LAN HY
Published: June 2020

Purpose of the Study: Dyslipidemia is one of the diabetic complications which is relevant to the disorder of interaction between glucose and lipid metabolism. In our preliminary studies, we found that Smad3 is the key pathogenic mediator in db/db mice. Metabolic symptoms in diabetes are improved in Smad3KO-db/db mice. Thus, we hypothesized that Smad3 is a therapeutic target for treatment of dyslipidemia in type 2 diabetes.

Methods: db/db mice were treated with Smad3 inhibitor SIS3 at the age of 4 weeks at the dose of 2.5mg/kg bw/day by intra peritoneal injection for 8 weeks. Control group db/db mice were treated with SIS3 solvent only. Molecules and cytokines involved in lipid metabolism were examined by Realtime-PCR, Western blotting, immunohistochemistry, ELISA for in vivo and in vitro experiments. The mechanism of Smad3 signaling interfering lipid metabolism was studied by Chip-sequencing and RNA sequencing.

Summary of the results: Blood high density lipoprotein (HDL) level was up regulated while low density lipoprotein (LDL) level and triglycerides were down regulated in Smad3 KO mice, which showed Smad3 is one of the main regulators in lipid metabolism. SIS3 treated mice showed significantly improved glycemia, lipidemia. Insulin sensitivity was ameliorated in SIS3 treatment group compared with control group. SIS3 treated Hepg2 cells and AML12 cells showed lower lipid absorbance than control group. RNA sequencing revealed that differentially expressed genes (DEGs) in concentrations of apolipoproteins A1 (ApoA1) was notable enriched in liver of Smad3KO mice, which also showed APOA1 has direct binding site with Smad3. We subsequently found that APOA1 was negatively regulated by Smad3 signaling therefore influence the lipid metabolism in type 2 diabetes.

Conclusion: Smad3 is a pathogenic mediator of diabetic metabolism. Treatment of type 2 diabetic mice with Smad3 inhibitor SIS3 improves lipidemia by enhancing the activity of DEGs in APOA1.

Disclosure

H. He: None. X. Huang: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. H. Lan: None.
58-LB: Barriers to Technology Use for Underserved Communities with Type 1 Diabetes
Authors: WALKER ASHBY F. , CUTTRISS NICOLAS , HALLER MICHAEL J. , FILIPP STEPHANIE L. , YABUT KATARINA , ANEZ-ZABALA CLAUDIA , HOOD KOREY K. , ROQUE XANADU , NARANJO DIANA , AULISIO GINA , ADDALA ANANTA , LOOK SYDNEY , GURKA MATTHEW J. , MAAHS DAVID M. ,   PROJECT ECHO DIABETES WORKING GROUP
Published: June 2020

Disparities in the use of CGMs and insulin pumps in T1D based on socioeconomic status (SES) and race/ethnicity are pronounced. However, systematic reports of perspectives from patients in vulnerable communities are limited. To better understand barriers, focus groups were conducted in Florida and California with adults with T1D. Selection criteria included hospitalization for DKA, HbA1C >9%, or receiving care at a Federally Qualified Health Center. A total of 16 focus groups were conducted in English or Spanish with 86 adults (Table 1). Transcript themes and pre-focus group demographic survey data were analyzed. In order of frequency, barriers to diabetes technology included: (1) provider-level (overtly blocked/discouraged by provider) (2) system-level (financial barriers related to coverage) and (3) individual-level (difficulty with use or preference issues). In Florida there was less technology use overall (38% had used CGMs in FL, 63% in CA; 43% had used pumps in FL, 69% in CA) and significant differences in pump use by SES (P=0.02 in FL, P=0.08 in CA) and race/ethnicity (P=0.01 in FL, P=0.80 in CA). In California there were significant differences in CGM use by race/ethnicity (P=0.05 in CA, P=0.56 in FL) and education level (P=0.02 in CA, P=0.90 in FL). These findings provide novel insights and demonstrate the need for multi-level interventions and further research on variations in technology use based on geographic location.

Disclosure

A.F. Walker: None. N. Cuttriss: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. S.L. Filipp: None. K. Yabut: None. C. Anez-Zabala: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. X. Roque: None. D. Naranjo: None. G. Aulisio: None. A. Addala: None. S. Look: None. M.J. Gurka: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
584-P: Optimal Utilisation of Statins in Real-World Settings
Authors: KRISHNA SESHADRI G. , DAS SAMBIT , NK NARAYANAN , MANOHAR SUDEEP P. , BS NARENDRA , MC DEEPAK , SHAH SANJIV , AHMED AFTAB , CHAVAN MAHESH , SATHYAKUMAR SAMANTHA , KOLUKULA VAMSI K.
Published: June 2020

Aim: The purpose of this retrospective data analysis is to assess prescription practices including appropriate use and dose of statins in patients with T2DM.

Methods: This is an observational retrospective data analysis of T2DM patients with dyslipidemia and who were on statin treatment for at least 6 months. Data for this study was obtained from EMRs of diabetes and endocrinology specialty outpatient clinics (n=35), pan India between Jan 2018 and May 2019. Patients aged <40 and >75 years were excluded from the analysis. Patient’s record with demographics, medical history, prescriptions (antidiabetes and statin drugs) and lab investigations data were collected.

Results: Of the total 45,205 diabetes patients, 15023(33%) were on statins. The mean age was 53.2 years, 64% were males and 36% were females. Final analysis included 4099 patients between ages 40 and 75 years on statin drugs along with antidiabetes drugs. Mean HbA1c, fasting and post-prandial blood glucose was 8.5%, 173mg/dL and 257 mg/dL, respectively. The lipid profile TC, TG, HDL, and LDL was 174mg/dL, 188 mg/dL, 41 mg/dL, and 107 mg/dL, respectively. Low-intensity statins (2539[62%]) were the most common prescriptions followed by moderate (1402[34%]) and high (158[4%]) intensity statins. Rosuvastatin (2615[64%]) was most commonly prescribed followed by atorvastatin (1302[32%]), and non-statin fenofibrate (182[4%]). 4% of the patients on low-intensity statins at the first visit moved to moderate or high dose intensity statins. In contrast, 2% of patients on moderate dose moved to low dose intensity.

Conclusion: In endocrine clinic population with 45205 patients only 33% of patients were on statins. In the population between 40 and 75, a majority were on low-intensity statins with relatively very few progressing to moderate and high-intensity statin. The low uptake of statins and low dose use indicates the need to increase awareness of appropriate patient selection and correct dose of statin use in the clinic population including referral and tertiary care clinics.

Disclosure

S.G. Krishna: None. S. Das: None. N. Nk: None. S.P. Manohar: None. N. Bs: None. D. Mc: None. S. Shah: None. A. Ahmed: None. M. Chavan: None. S. Sathyakumar: None. V.K. Kolukula: None.
593-P: Cold Atmospheric Pressure Plasma for Accelerated Wound Healing in Diabetic Foot: The Prospective, Randomized, Placebo-Controlled KPW-Trial
Authors: STRATMANN BERND , COSTEA TANIA-CRISTINA , NOLTE CATHARINA , HILLER JONAS , SCHMIDT JÖRN , REINDEL JÖRG , MASUR KAI , MOTZ WOLFGANG H. , TIMM JÜRGEN , KERNER WOLFGANG , TSCHOEPE DIETHELM
Published: June 2020

Diabetic foot is a common complication of diabetes mellitus and requires specialized treatment. Cold plasma has demonstrated beneficial effects on wound infection and healing in case reports. The “Kaltplasma Wund (KPW)-Trial” aimed to analyse whether the application of cold plasma accelerates wound healing in diabetic foot compared to standard care therapy. It was a prospective, randomized, placebo-controlled, patient-blinded, bi-center trial. People with diabetes mellitus and diabetic foot WA 1B or 2B were eligible. Each wound was randomized separately. Wounds were treated additionally with cold plasma generated from inert argon gas in an atmospheric pressure plasma jet or placebo. Primary endpoints were reduction in wound size, in clinical infection and microbial load compared to beginning. Important secondary endpoints were time to significant wound reduction (>10%), and to reduction of infection. Ad hoc we analysed the time to 20% wound reduction. In addition, wound dressings from 15 patients per group were analysed for expression of VEGF via ELISA. In total 65 cases were included in the study and 62 were considerable for final evaluation. Plasma therapy yielded in a significant increase of wound healing, both in total area reduction (-26.31±11.72, p=0.0248 vs. placebo) as well as time to significant wound area reduction (10% from baseline, -1.60±0.58, p=0.0085 vs. placebo). The effect was even more significant, if the reduction level was set to 20% (p<0.0001). Reduction of infection and microbial load was not significantly pronounced in plasma therapy. Regarding the expression of VEGF wounds in the plasma group presented throughout the study with at most visits significant higher levels of baseline corrected VEGF than wounds randomized to placebo therapy. Cold plasma therapy revealed beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection.

Disclosure

B. Stratmann: Speaker’s Bureau; Self; AstraZeneca, Neoplas Tools GmbH. T. Costea: Other Relationship; Self; Merck Sharp & Dohme Corp. C. Nolte: None. J. Hiller: None. J. Schmidt: None. J. Reindel: None. K. Masur: None. W.H. Motz: None. J. Timm: None. W. Kerner: None. D. Tschoepe: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Neoplas tools GmbH.
596-P: Emergence of Peripheral Arterial Disease in Persons with Diabetes, Dar Es Salaam, Tanzania: A Need for Clinical and Public Health Intervention
Authors: ABBAS ZULFIQARALI G. , ARCHIBALD LENNOX K.
Published: June 2020

Background: Surveillance data from Tanzania during the 1980s and 1990s had shown that the vast majority (>80%) of foot ulcers in persons with diabetes (DM) were neuropathic in origin and not associated with peripheral arterial disease (PAD). However, over the past decade, clinicians have observed an increase in the occurrence of PAD among persons who attend DM clinics at Muhimbili National Hospital (MNH) in Dar es Salaam. We therefore carried out this study to characterize the epidemiology of PAD in a large DM population and identify risk factors.

Methods: During Jan 2014 through Dec 2018, (study-period) and following informed consent, patients who attended MNH DM clinics with foot ulcers were evaluated. We recorded detailed epidemiologic and clinical data, and outcomes. Logistic regression was performed and adjusted odds ratio (AOR) and 95% confidence intervals (CI) calculated.

Results: Of 5,687 enrolled subjects, 3,621 (65%) were male; median BMI was 26.5; median age and diabetes duration were 57 and 8 years, respectively. All patients had some degree of PN; 28% had PAD; ischemic heart disease was uncommon (0.4%). Independent factors associated with PAD included hypertension (AOR: 1.3, CI: 1.1-1.5); tobacco (AOR: 1.4, CI: 1.2-1.7); major amputation (AOR: 3.2, CI: 1.9-5.9); or death (AOR: 2.2, (1.6-3.0). Indians and Arabs were significantly more likely than ethnic Africans to have PAD (p<0.01).

Conclusion: We documented a significant increase in the prevalence of PAD in DM patients in Tanzania—a problem that heretofore was not appreciated. The increase appears to be linked to hypertension and tobacco and likely reflects increasing urbanization of African communities across the African continent, more sedentary lifestyles, lack of exercise, and diet. Underscoring these risks are changes in population demography. PAD is now playing a more substantial role in the pathogenesis of DM foot ulcer in Africa than was previously thought.

Disclosure

Z.G. Abbas: None. L.K. Archibald: None.
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>24), higher prevalence of Charcot foot was noted compared with those with BMI<24 (p<0.05). The Charcot foot patients have a 7-times higher risk of amputation compared with patients with chronic ulcer (p<0.05), 2.6-times higher risk compared with patients with peripheral arterial occlusion diseases (p<0.05), and 5-times higher risk with patients with osteomyelitis (p<0.05). A Higher risk of amputation was also noted in Charcot foot patients with more than 2 times debridement (OR:5.05, p<0.05). A higher prevalence of osteomyelitis was noted in patients of Charcot foot with chronic ulcer than those without chronic ulcer (p<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<0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p<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 <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<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>8% or systolic blood pressure (SBP)>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
617-P: Effect of Improving Postprandial Glucose by Eating with the Nondominant Hand in Japanese Patients with Type 2 Diabetes
Authors: NISHIMORI EITA , NAKA MOTOJI
Published: June 2020

Background: Diabetes patients need to improve postprandial hyperglycemia. Eating slowly is effective for improving postprandial glucose (PPG), and a simple method is required in daily life. This study aimed to determine the effect of improving PPG by eating with the non-dominant hand in Japanese patients with type 2 diabetes (T2D).

Methods: This was a prospective, non-randomized, open-labeled, single-arm study that enrolled 10 patients of T2D who hospitalized in Asama General hospital for glycemic control. We measured glucose levels, C-peptide concentrations, and eating styles when subjects ate with the dominant hand and the non-dominant hand. Chopsticks were used for meals. The mean daily intake of energy, carbohydrate, protein, and fat was set individually and was unchanged during the period of this study. Participants were instructed to eat vegetables fast and carbohydrates last, and to chew 30 times per bite.

Results: Subjects (5F/5M) were average age 54 years, BMI 26 kg/m2, HbA1c 8.6%, of which 7 used only oral hypoglycemic drugs and 3 used injections. Each PPG and PPG AUC decreased with the non-dominant hand compared to the dominant hand, especially at breakfast (p<0.001) and dinner (p=0.015). Delta PPG and delta C-peptide of breakfast were 76 mg/dl and 3.4 ng/ml for the dominant hand, and 39 mg/dl and 2.4 ng/ml for the non-dominant hand, both of which were significantly lower in the non-dominant hand (PPG p=0.002, C-peptide p=0.015). Each meal time was significantly extended from the dominant hand to the non-dominant hand (breakfast time 18 vs. 23, lunch 18 vs. 24, dinner 18 vs. 27 minutes, p<0.01), and the number of chewing per bite at breakfast significantly increased (22 vs. 30 times/bite, p<0.001).

Conclusions: Our findings suggested that eating with the non-dominant hand was effective in improving PPG in Japanese patients with T2D by prolonging the meal time and increasing the number of chewing per bite.

Disclosure

E. Nishimori: None. M. Naka: None.
618-P: Machine Learning in Predicting Poor Glycemic Outcomes
Authors: ALQUADAN HAMMAM , SIMINERIO LINDA M. , KRALL JODI T. , NG JASON
Published: June 2020

With 1.5 million Americans diagnosed with diabetes mellitus (DM) annually, 84.1 million with prediabetes, and 245 billion in medical costs, efforts to characterize those at highest risk are warranted. Predictive modeling is a methodology that can proactively identify patients and allocate resources like a DM education intervention, known to ensure effective, cost-saving care.

Members of the University of Pittsburgh Medical Center (UPMC) endocrine division partnered with the Clinical Data Analytics Department to develop a predictive model using clinical data from patient electronic medical records (EMR), Medical and socioeconomic profiles were used to predict future glycemic control from any patient with a type 2 DM diagnosis or any patient with two HbA1c readings ≥6.5% within 1 year.

SHapley Additive exPlanations (SHAP), atheoretic approach used to explain output of a machine learning model, was used to analyze variables of 38,173 patients meeting inclusion criteria. Prior elevated HbA1C levels, younger age at presentation, and previous insulin therapy provided the highest prediction of future poor glycemic control.

Predictive modeling is a useful method to foretell future glycemic control. Identifying patients at “high risk” for poor outcomes can allow for efficient deployment early in the disease course for DE services proven to improve outcomes with the potential to reduce health care costs.

Disclosure

H. Alquadan: None. L.M. Siminerio: Research Support; Self; Becton, Dickinson and Company. J.T. Krall: Research Support; Self; Becton, Dickinson and Company. J. Ng: None.
622-P: Systematic Screening and Assessment of Diabetes Prevention and Self-Management Programs That Utilize Telehealth Technology
Authors: MENSA-WILMOT YVONNE , BONNER TIMETHIA , AYALA-PERALES MARIA M. , MENSA-KWAO AUGUSTINA , BOWEN SHELLY-ANN , GREENBERG MICHAEL , DAWKINS-LYN NICOLA , RUTLEDGE GIA E.
Published: June 2020

Background: Remote delivery of health care services through telehealth technology holds promise for expanding access to and engaging individuals in underserved communities. Systematic Screening and Assessment and Evaluability Assessment methods were used to identify and evaluate promising CDC-recognized National Diabetes Prevention Program Lifestyle Change and Diabetes Self-Management Education and Support (DSMES) programs utilizing telehealth technology.

Objective: To describe how 8 Lifestyle Change and DSMES programs utilize telehealth technologies effectively to expand access to services in underserved communities.

Methods: Eight effective programs were selected to participate in an in-depth study. Information was gathered to understand activities, adaptations, and implementation challenges through in-depth interviews with stakeholders and on-site observation.

Results: In all program sites, telehealth technology seamlessly integrated into existing program models to increase patient engagement and experience. Programs offered various tailored products based on the curriculums to reinforce prevention and self-management education. Automation of several program processes reduced burden on health coaches and diabetes educators, and improved data quality and analysis capabilities. Bi-directional communication between providers and programs was key to gaining provider buy-in and increasing referrals. Understanding activities being implemented by effective programs is crucial for expanding use of telehealth technologies.

Conclusion: This project provides valuable practice-based evidence for planning and implementing diabetes prevention and management interventions.

Disclosure

Y. Mensa-Wilmot: None. T. Bonner: None. M.M. Ayala-Perales: None. A. Mensa-Kwao: None. S. Bowen: None. M. Greenberg: None. N. Dawkins-Lyn: None. G.E. Rutledge: None.
626-P: Online Patient/Caregiver Education on Practical Use of CGM Can Improve Knowledge and Confidence as well as Prompt Real-Life Changes
Authors: LARKIN AMY , LACOUTURE MICHAEL
Published: June 2020

We sought to measure the impact of online education for patients/caregivers on knowledge and confidence as well as on prompting changes in daily life. The education was available online, and comprised of text and integrated visuals. Demographic questions were asked prior to starting the education. A knowledge question was asked both before and after the activity to assess learning gains, as well as intent to change and confidence questions at the end. Absolute improvements were calculated for pre/post questions. The activity launched August 31, 2019, and preliminary data collected through October 30, 2019. To date, 4,631 learners have participated in the patient/caregiver activity, “AGP: What Do I Need to Know?” Completers of all questions (included in outcomes analysis): 755 Demographics: 52% female; 63% white, non-Hispanic; 70% over the age of 54; 71% have diabetes, 18% were interested in learning more about diabetes and the AGP Knowledge changes: 10% improvement in recognizing the benefits of an AGP report (78% pre to 88% post) Intent-to-act: 80% plan to talk to their HCP about if CGM can help them better monitor their diabetes Confidence changes: 88% reported increased confidence using an AGP report to interpret trends in glucose levels The metrics and outcomes gathered in this assessment are a strong indicator that these patient/caregiver-focused online educational activities improved knowledge and confidence and prompted intent to act by patients/caregivers related to CGM use in diabetes management.

Disclosure

A. Larkin: None. M. LaCouture: None.

Funding

Abbott Diabetes Care