bluuebunny/crossref_metadata_2025_split huggingface dataset:
514-P: Adaptive Downregulation of NLRP3 Inflammasome Expression in Human Renal Tubular Epithelia in the Hyperglycemic and Hyperuricemic Culture
Authors: CIYING CHEN , RAN JIANMIN , CHEN CHUPING , ZHU PING , TAN RONGSHAO , LIU YAN 
Published: June 2020

Background: Hyperuricemia has been an independent risk factor for diabetic kidney disease. Previous studies showed that hyperuricemia may induce interstitial infiltration of macrophages and activates its NLRP3 inflammasome. Meanwhile, there has been proved that an inner NLRP3 system exists in human tubular epithelia. Here we try to find how glucose and uric acid (UA) affect NLRP3 inflammasome in cultivating tubular epithelia.
Methods: HK-2 cells were cultivated. Experiment was designed according to a 2×3×2 multifactorial style. Double glucose concentrations (5.5MM and 25MM) crossed with three escalated UA concentration (0MM, 0.2MM, and 0.4MM), as well as Mcc950 (0MM and 0.1MM), an specific blocker for NLRP3 inflammasome. Morphology of HK-2 cells were observed. Supernatant concentrations and gene expressions of pivotal factors involved in NLRP3 inflammasome pathway including NLRP3, ASC, caspase-1, IL-1β and IL-18 were detected.
Results: 1) Morphology: As concentrations of glucose and UA increased, HK-2 cells obviously became floating and fragmental. 2) Genes: Except for Caspase-1, gene expressions of other four components were significantly inhibited in hyperglycemic state. Expressions of five genes were all decreased in euglycemic but unchanged in hyperglycemic state when UA increased. Mcc950 treatment significantly increased gene expressions of NLRP3, ASC, IL-1β and IL-18 in euglycemic but kept them unchanged in hyperglycemic state as UA increased. 3) ELISA: Supernatant IL-1β and IL-18, two effector molecules of NLRP3 inflammasome, were significantly decreased after stimulation with increased glucose or UA cascade. Interestingly, Mcc950 treatment further decreased concentrations of two molecules when UA stepwisely increased.
Conclusions: The inner NLRP3 inflammasome counter-regulates effects of hyperglycemia and hyperuricemia. Mcc950 may block the downstream points to reduce IL-1β and IL-18 production directly.

Disclosure
C. Ciying: None. J. Ran: None. C. Chen: None. P. Zhu: None. R. Tan: None. Y. Liu: None.

Funding
Guangdong Science and Technology Project Fund (2014B030303002); Guangdong Provincial Academician Workstation Fund (2017B090904027)
519-P: Comparison of Chronic Kidney Disease Risk Factors between Normoalbuminuric and Albuminuric Patients with Diagnosed Diabetes and Reduced Kidney Function
Authors: MOSSLEMI MITRA , HANNA RAMY M. , RHEE CONNIE , KALANTAR-ZADEH KAMYAR , STREJA ELANI 
Published: June 2020

The prevalence of normoalbuminuric diabetic kidney disease (DKD) has increased in the past 20 years in the U.S. While previous studies reported the significance of nonalbuminurics pathway to kidney function loss in DKD, the factors associated with the nonalbuminuric kidney function decline remains to be elucidated. This study aimed to compare the CKD risk factors between nonalbuminuric and albuminuric DKD. Among NHANES participants (1999-2016) with diagnosed diabetes and reduced eGFR (&lt; 60), we compared CKD risk factors (including demographics and CKD diagnosis status) between patients with normoalbuminuria (ACR&lt;30) and albuminuria (ACR ≥ 30) using univariate and multivariable analyses. In our DKD cohort, there were 1479 (63%) normoalbuminuric and 1027 (37%) albuminuric cases. Risk factors that significantly differed between albuminuric statuses are presented in Table [Table]. In the multivariable model, age, gender, and DBP were not significantly associated with albuminuric status, while CKD diagnosis status was the strongest predictor followed by eGFR. Normoalbuminuria in patients with diabetes and reduced eGFR is associated with a seemingly healthier lab profile and lower odds of being diagnosed with CKD. Future studies should examine novel markers for detection of and protection against kidney function decline in nonalbuminuric DKD.

Disclosure
M. Mosslemi: None. R.M. Hanna: None. C. Rhee: Research Support; Self; Dexcom, Inc. K. Kalantar-Zadeh: None. E. Streja: None.
528-P: Relationship between Bone Mineral Density and Diabetic Nephropathy in Adults with Type 1 Diabetes
Authors: LARA CAROLINA , RODRIGUEZ FATIMA , VIVEROS-RUIZ TANNIA , ALMEDA-VALDES PALOMA , URIBE DANIEL , RIVAS BERNARDETTE , PEDRAZA NATALIA RAMIREZ , GARAY MORA JUAN A. 
Published: June 2020

Objective: Osteoporosis is typically identified as a disease of postmenopausal women, however; it has been observed that in patients with type 1 diabetes (T1D) fractures associated with osteoporosis four to six times more common, in both sexes and at an early age (≈ 50 years). The objective of this study was to find associations between the bone mineral density (BMD), T-score and Z-score at the femoral neck, hip and spine and selected characteristics of patients with T1D.
Methods: BMD of patients with T1D was evaluated with DXA (GE Healthcare Lunar). A correlation analysis was performed to identify associations between glycated hemoglobin, 25-hydroxyvitamin D concentration, years since diagnosis and diabetic, estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR).
Results: We included 43 patients, with a mean age of 38.1 years, the mean BMD in the femoral neck was 0.94±0.13, in the hip 0.93±0.14 and the spine 1.11±0.13. We observed a negative correlation between the years since diagnosis of T1D and the BMD and T-score in the femoral neck and hip. There was a negative correlation between the ACR and the BMD, T-score and Z-score in the femoral neck and total hip and a positive correlation between the eGFR and the BMD and T-score in the femoral neck and hip.
Conclusions: In this study we identify some factors that might impact and decrease the BMD in patients with T1D including long time since diagnosis, older age of patients and presence of diabetic nephropathy. The ACR could be an indicator of early bone metabolic changes in patients with T1D. Further studies are required to confirm this association and to define the optimal age for BMD evaluation in patients with T1D.

Disclosure
C. Lara: None. F. Rodriguez: None. T. Viveros-Ruiz: None. P. Almeda-Valdes: None. D. Uribe: None. B. Rivas: None. N. Ramirez Pedraza: None. J.A. Garay Mora: None.
535-P: Neurotensin Improves Endothelial Progenitor Cell Function in Diabetic Wound Healing
Authors: LEAL ERMELINDO C. , FIGUEIREDO ANA , CARVALHO EUGENIA 
Published: June 2020

Diabetic neuropathy plays an important role in the development of chronic wounds. Endothelial progenitor cells (EPCs) are known important regulators of wound angiogenesis. However, the role of neuropeptides in EPC function, and particularly Neurotensin (NT), is unknown in diabetic wound healing. EPCs isolated from normal mice were cultured in high glucose (25 mM) or normoglicemia (5.5 mM) and treated with NT (25-400 nM) for 3 days. Moreover, EPCs isolated from streptozotocin (STZ)-induced diabetic mice were treated with NT (100 nM) for 3 days. Subsequently, EPC viability, cell adhesion and reactive oxygen species (ROS) levels were evaluated. To the in vivo wound healing model, 6 mm wounds were created in the dorsum of diabetic mice and wound progression was followed up to day 10. The wound edges were injected with ex-vivo diabetic bone marrow derived EPCs treated in culture with NT (100 nM) for 3 days, or EPCs without NT treatment, or vehicle. Angiogenesis was evaluated by immunohistochemistry. The viability of EPCs cultured under high glucose or EPCs from diabetic mice was improved by NT treatment. Also, EPCs from diabetic mice showed decreased adhesion (58% of control, p&lt;0.05) and increased ROS levels (148% of control, p&lt;0.05) when compared to control EPCs, and these effects were reversed by NT treatment. In addition, NT-treated EPCs, from diabetic mice, improved wound closure (day 10, 4% of original wound size) when compared with non-treated EPCs or vehicle (day 10, 32% and 35% of original wound size, respectively, p&lt;0.05). Furthermore, NT-treated EPCs, from diabetic mice, increased neovascularization at the wound site (153% of vehicle, p&lt;0.05) when compared with non-treated EPCs (115% of vehicle) or vehicle. These results show that neurotensin is able to improve the function of EPCs from diabetic animals, which are able to improve wound healing by promoting angiogenesis. The restoration of EPC function by neurotensin could improve their therapeutic effect for the treatment of chronic diabetic wounds.

Disclosure
E.C. Leal: None. A. Figueiredo: None. E. Carvalho: None.

Funding
Portuguese Foundation for Science and Technology; European Foundation for the Study of Diabetes; Portuguese Society of Diabetology
56-LB: Trauma and Anxiety Effects on Adherence in Pediatric Type 1 Diabetes Mellitus
Authors: RAJ RISHI , NGUYEN MAI , MORALES ALBA , MEADOWS AMY L. 
Published: June 2020

Background: Psychiatric factors, such as depression, anxiety, and life stressors, have been shown to negatively affect diabetes adherence and glycemic control in children and adolescents. However, less is known about how trauma exposure and symptoms of post-traumatic stress disorder (PTSD) may impact adherence and glycemic control.
Objectives: Determine the rates of trauma exposure and PTSD symptoms in patients ages 7-21 with type 1 diabetes (T1DM). Examine the relationship between trauma exposure, PTSD, Anxiety, behavioral adherence and glycemic control.
Methods: We enrolled 99 patients (mean age 13.8 ± 3.5 years, 51.5% female) who had been diagnosed with T1DM for at least 6 months and underwent standardized psychiatric screening questionnaires during their clinic visits. HbA1c at goal was defined by HbA1c &lt; 7.5% and behavioral adherence were defined by self-monitoring of blood glucose (SMBG) ≥ 4/day or continuous glucose monitoring (CGM) calibration ≥ 2/day and/or CGM use ≥ 75%. All participants and/or their guardians provided assent and consent. Chi-square tests were used to assess the relationships between trauma, PTSD, anxiety and behavioral adherence. One-way ANOVA was conducted to examine group differences between HbA1c scores and the presence of suicidal ideation.
Results: 38.4% of participants had trauma symptoms and functional impairment. Rates of trauma secondary to accidental injury, medical traumatic stress, natural disaster and witness to family violence were 28.3%, 22.2%, 10.1%, and 6.1%, respectively. Neither trauma exposure nor PTSD predicted diabetes adherence. Anxiety was significantly associated with diabetes nonadherence (p=0.006). The group with suicidal ideation had higher HbA1c compared to the group without suicidal ideation (8.92 ± 1.40 vs. 8.30 ± 1.35, p=0.047).
Conclusions: Although trauma was common among young patients with T1DM, other factors, such as anxiety and suicidal ideation, maybe more important indicators of adherence and glycemic control.

Disclosure
R. Raj: None. M. Nguyen: None. A. Morales: None. A.L. Meadows: None.

Funding
Children’s Miracle Network/Kentucky Children’s Hospital Research Fund; National Institutes of Health (UL1TR001998)
562-P: Influence of Glycemic Control and Variability on Diabetic Retinopathy in Type 1 Diabetes Patients on Continuous Subcutaneous Insulin Infusion Therapy
Authors: LECUMBERRI EDURNE , BENGOA NURIA , ARGÜESO MARÍA FERNÁNDEZ , NATTERO CHÁVEZ LÍA 
Published: June 2020

Introduction: There is scarce evidence demonstrating a relationship between glycemic control or glycemic variability with diabetic retinopathy (DR).
Objectives: We aimed to determine the prevalence of DR and its association with time in range (TIR), and other association factors.
Methods: We performed a retrospective observational study with 130 T1DM patients on continuous subcutaneous insulin infusion (CSII). Data of the three previous months were downloaded and analyzed.
Results: Mean age was 37±13 years-old. 51.5% were female. Mean BMI was 24.8±4.0 Kg/m2. Duration of T1DM was 21±10 years. The mean HbA1c was 7.1±0.8%; before CSII 7.4±1.0%. Mean LDL-c was 100±26 mg/dL. The prevalence of DR was 20.8% (95%CI: 14.7 - 28.5); 19.2% non-proliferative DR and 1.5% proliferative DR. Most glycemic control and variability parameters were significantly higher in the DR+ group (Table 1). After applying the stepwise logistic regression model (p&lt;0.001, R2 0.561), the association factors for developing DR were: LDL-c, ExpB 0.97 (95%CI 0.95-0.99); duration of DM, ExpB 1.26 (95%CI 1.12-1.41); and HbA1c before CSII, ExpB 2.24 (95%CI 1.17-4.31).
Conclusions: Lower TIR and higher time in hyperglycemia were observed in patients with DR. LDL-c levels, long duration of DM and higher HbA1c before CSII were independent association factors for the development of DR.

Disclosure
E. Lecumberri: None. N. Bengoa: None. M. Fernández Argüeso: None. L. Nattero Chávez: None.
564-P: Differences in Diabetic Retinopathy Prevalence and Progression between Aboriginal and Anglo-Celt Australians: The Fremantle Diabetes Study Phase II
Authors: DRINKWATER JOCELYN J. , DAVIS WENDY A. , TURNER ANGUS W. , DAVIS TIMOTHY 
Published: June 2020

Background: There are limited contemporary data on the prevalence and progression of diabetic retinopathy (DR) in urban-dwelling Aboriginal Australians. We therefore compared the prevalence of DR and cumulative incidence of new/worsening DR (NWDR) between Aboriginal and Anglo-Celt Australians with type 2 diabetes (T2D) in the representative community-based Fremantle Diabetes Study Phase II (FDS2).
Methods: From 2008 to 2011, 932 Anglo-Celt and Aboriginal FDS2 participants with T2D underwent comprehensive baseline assessments and were invited to biennial reviews. Ethnic status was based on self-selection, country/countries of birth and parents’ birth, language(s) spoken at home, and country of grandparents’ birth. Fundus photographs were graded according to the Early Treatment Diabetic Retinopathy Study protocol. Prevalence of DR and cumulative incidence of NWDR for each ethnic group, and unadjusted and adjusted odds ratios (ORs), were calculated.
Results: Baseline DR data was available for 911 (97.7%) participants (mean age 66.0 years, median T2D duration 8.4 years, 49.7% males). There were 817 Anglo-Celt and 94 Aboriginal participants. Of these, 56% had follow-up data. Baseline prevalence of any DR was 33.0% in Anglo-Celts and 52.1% in Aboriginals (P&lt;0.001). During 4.2±0.4 years’ follow-up, the cumulative incidence of NWDR was 6.7% and 23.5%, respectively (P&lt;0.001). The unadjusted OR (95% CI) for Aboriginals for any DR and NWDR were 2.21 (1.43-3.39) and 4.32 (1.33-13.98), respectively. These ORs were attenuated after age and sex adjustment (1.21 (1.10-1.33) and 4.1 (1.2-14.1), respectively) but were no longer significant after adjusting for other DR risk factors including HbA1c and systolic blood pressure.
Conclusions: Urban dwelling Aboriginal Australians have substantial DR prevalence and progression, highlighting the need for better access to culturally appropriate management.

Disclosure
J.J. Drinkwater: None. W.A. Davis: Advisory Panel; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Proteomics International. Other Relationship; Spouse/Partner; Proteomics International. A.W. Turner: None. T. Davis: Advisory Panel; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Spouse/Partner; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Protemics International. Other Relationship; Spouse/Partner; Protemics International.

Funding
University of Western Australia; Australian Government Training Program; National Health and Medical Research Council of Australia
569-P: Plasma Metabolomic Profiling of Diabetic Macular Edema
Authors: XIAORONG ZHU 
Published: June 2020

Background: Diabetic macular edema (DME), a sight-threatening retinopathy, is a leading cause of vision loss in persons with diabetes mellitus. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop DME, suggesting the existence of other potential pathogenic factors underlying DME. This study aimed to investigate the plasma metabotype of patients with DME and to identify novel metabolite markers for DME. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of DME.
Methods: To match clinical parameters between case and control subjects, patients with DME (DME, n=30) or those with diabetes but without DME (Control, n=30) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS).
Results: A total of 188 distinct metabolites between DME and Control groups were identified (VIP &gt; 1, Fold Change &gt; 1.5 or &lt; 0.5, and P &lt; 0.05). These metabolites mainly included Lipids and lipid-like molecules (71%), organic acids and derivatives (17%), Organic oxygen compounds (8%) and others. The distinct metabolites between DME and Control groups were enriched in 5 KEGG pathways, namely, lysine degradation, arachidonic acid metabolism, riboflavin metabolism, sulfur relay system, and thyroid hormone synthesis. Finally, 4 metabolites were selected as candidate biomarkers for DME, namely, Violaxanthin, uridine, D-Glucopyranuronic acid, and Capryloylglycine. The area under the curve for these biomarkers were 0.89, 0.85, 0.86, and 0.82, respectively.
Conclusions: This study suggested that impairment in the metabolism and 4 potential metabolites were identified as metabolic dysregulation associated with DME, which might provide insights into potential new pathogenic pathways for DME.

Disclosure
X. Zhu: None.

Funding
National Key Research and Development Program of China (2017YFC0909600)
583-P: Effects and Safety of Pemafibrate, a Novel Hypolipidemic Agent in Japanese Type 2 Diabetes Patients Receiving Statins
Authors: KUSUNOKI MASATAKA , SATO DAISUKE , SAKAZAKI TAKAHIKO , NATSUME YUKIE , MIYATA TETSURO 
Published: June 2020

The combination therapy of statins and fibrates may increase the risk of hepatic dysfunction and myopathy, so this combination was contraindicated in patients with renal impairment and required careful administration even for patients with normal renal function. However, in Japan, patients with renal impairment were excluded from the relative contraindication category in 2018.
In the present study, we additionally administered 0.2 mg/day pemafibrate (PFB), a novel fibrate, for 6 months to 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and examined the efficacy and safety of the combination therapy in comparison with a PFB monotherapy group.
In the combination group, a significant decrease in serum total cholesterol level was observed after 6 months of PFB treatment compared to baseline, along with increase in HDL-cholesterol. A significant decrease in serum triglyceride and a significant increase in HbA1c were observed in both groups. Significant decreases in serum creatinine kinase, which is an indicator of myopathy, and serum γ-GTP, a parameter of hepatic dysfunction, were observed in the combination group.
These results demonstrated that the statin-PFB combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

Disclosure
M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. D. Sato: None. T. Sakazaki: None. Y. Natsume: None. T. Miyata: None.
589-P: Impaired Endothelial Nrf2 Expression Reduces Wound Neovascularization in Diabetic Mice
Authors: LEE JASMINE , VILLARREAL PONCE ALVARO P. , DAVID JOSHUA A. , KUHN JOSEPH , KWONG JENNIFER , CERADINI DANIEL 
Published: June 2020

The global cost of diabetes in the U.S. is 1.3 trillion dollars, with chronic diabetic foot ulcers accounting for up to 13 billion dollars annually. An underlying factor that contributes to the chronicity of these wounds is poor vascular flow, which impedes physiologic wound healing. Here, using an in vivo murine model of wound healing, we demonstrate that Nrf2 expression in endothelial cells is necessary for physiologic neovascularization. Full-thickness 10 mm stented excisional wounds were created on the dorsa of double transgenic mouse with inducible conditional deletion of Nrf2 in cadherin 5 expressing endothelial cells (KO), wildtype (WT), and heterozygous mice. Time to wound closure was delayed in the KO compared to WT mice (KO 33.0±1.73 days vs. WT 14.0±0 days) and Nrf2 KO healed similarly to diabetic mice (KO 33.0±1.73 days vs. Diabetic 31.0±1.41 days). Endothelial cells isolated from the wounds of KO mice via flow cytometry demonstrated significantly decreased angiogenic functionality when compared to heterozygous controls. KO endothelial cells formed significantly fewer branches (KO 64.75±14.81 branches/cm2 vs. control 282.8±46.7 branches/cm2, p=0.014) and fewer branching points (KO 39.0±5.18 branching points/cm2 vs. Control 150.8±15.34 branching points/cm2, p=0.0031), indicating impaired angiogenic activity. Immunofluorescent staining of endothelial cells within the wound beds of KO also demonstrate decreased vascularity compared to WT controls. We looked at regulation of the CXCR4/SDF-1 axis, key to angiogenesis, using C166 mouse endothelial cells. Nrf2 knockdown cells in hypoxia, results in reduced Nrf2 levels by 76.5% (p=0.001) and that of downstream marker NQO1 by 66.4% (p=0.02). Expression of CXCR4 and SDF-1 decreased 61.7% (p=0.001) and 47.6% (p=0.02) respectively. These findings suggest that the Nrf2 dysregulation associated with diabetes may contribute to the impaired angiogenesis and decreased revascularization present in chronic diabetic wounds.

Disclosure
J. Lee: None. A.P. Villarreal Ponce: None. J.A. David: None. J. Kuhn: None. J. Kwong: None. D. Ceradini: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-16-ACE-08 to D.C.)