bluuebunny/crossref_metadata_2025_split huggingface dataset:
42-OR: Effects of Oxidative Phosphorylation Complexes Defects on Beta-Cell Function
Authors: LANG ANNA L. , NISSANKA NADEE , TAMAYO ALEJANDRO M. , MORAES CARLOS T. , CAICEDO ALEJANDRO 
Published: June 2021

Background: The pancreatic beta cell is a highly metabolic cell type relying on mitochondrial metabolism for stimulus-secretion coupling. Specifically, the ATP-producing oxidative phosphorylation (OXPHOS) pathway is central to insulin secretion. Although disruptions in ATP production occur in beta cell dysfunction, the exact mechanisms remain unknown. We generated beta cell specific inducible knockout mouse models of OXPHOS Complex I, III, and IV to determine the direct effects of each OXPHOS complex on beta cell function. We hypothesize that individual complexes contribute distinctly to beta cell function.
Methods: Male OXPHOSf/f - MIPcreERT mice were administered tamoxifen (150mg/kg) or vehicle by I.P. injection for 5 days. Glucose and insulin tolerance were assessed 3 weeks after induction. Mice were anesthetized with ketamine/xylazine and perfused with PBS followed by 4% PFA. Pancreata were dissected, embedded in OCT, and cut for islet hormone staining. To determine mitochondrial respiration, Seahorse Bioenergetic Flux analysis was performed on isolated islets from all groups.
Results: Complex III knockout mice developed severe hyperglycemia and glucose intolerance at 3 weeks post-induction, while insulin tolerance remained the same. The other two models showed a trend towards hyperglycemia starting at 5 weeks, but retained their ability to regulate glucose at 3 weeks. Interestingly, no changes in islet cytoarchitecture were observed in any of the groups. Western blot analyses on islet lysates confirmed a marked, and comparable knockdown of the targeted complex in all 3 models. Defects were seen in glucose-stimulated mitochondrial respiration for all knockout models at 3 weeks.
Conclusions: Mice with Complex III deficient beta cells showed a robust diabetic phenotype compared to Complexes I and IV models despite all models having significant knockdown of the targeted complex. This supports the hypothesis that specific OXPHOS complexes contribute differentially to beta cell function.

Disclosure
A. L. Lang: None. N. Nissanka: None. A. M. Tamayo: None. C. T. Moraes: None. A. Caicedo: None.

Funding
National Institute of Environmental Health Sciences (R33ES025673)
428-P: The Association between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Diabetic Retinopathy
Authors: TAN YING , TANG XIXIANG , CHEN YANMING 
Published: June 2021

Retinal chronic inflammation plays a pivotal role in the development of diabetic retinopathy (DR). Monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is associated with inflammatory and oxidative stress status. Some studies suggest that an elevated MHR can be a biomarker for diabetic complications. However, there are not adequate studies on MHR and DR. A total of 771 patients with T2DM and 607 healthy controls were included in this cross-sectional study. MHR and eye examination were checked. The predictive role of MHR on the development of DR in T2DM patients was analyzed. The MHR in patients with DR was significantly higher than that of both the non-DR diabetic patients (P &lt; 0.05) and the healthy controls (P &lt; 0.01). No significance were observed in the MHR of different DR severity grades. Moreover, MHR was similar between patients with non-macular edema and macular edema. Logistic regression analysis demonstrated that MHR was independently associated with the development of DR in diabetic patients [OR =1.377, 95% CI: 1.176-1.613, P &lt; 0.01]. MHR can be an independent predictor of the development of DR in patients with T2DM.

Disclosure
Y. Tan: None. X. Tang: None. Y. Chen: None.
430-P: Urinary Proteome and Diabetic Retinopathy in the Direct-Protect 1 and 2 Trials
Authors: CUROVIC VIKTOR ROTBAIN , MAGALHÃES PEDRO , HE TIANLIN , HANSEN TINE W. , MISCHAK HARALD , ROSSING PETER 
Published: June 2021

Background: Given the association of diabetic retinopathy (DR) to diabetic kidney disease, we investigated the urinary proteome to the presence and deterioration of DR in type 1 and type 2 diabetes in a post-hoc analysis of studies investigating the effect of candesartan on the progression of DR.
Methods: Baseline urinary proteomic analysis was performed in 783 and 792 randomly chosen subjects from two RCTs: DIRECT-Protect 1 and 2. Endpoints were two-step and three-step change in DR score according to the Early Treatment of Diabetic Retinopathy Study protocol. Peptide levels were correlated to baseline DR score, using Spearman rank correlation (association presented as Rho), in a discovery set of 2/3 of participants in DIRECT-Protect 1. Identified peptide fragments were then tested cross-sectionally in a validation set of the remaining 1/3 in DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts in relation to baseline DR. Finally, peptides validated in the entire cohorts were tested longitudinally. Adjustment included sex, age, diabetes duration, smoking, total cholesterol, HbA1c, SBP, UAER, serum creatinine, and randomization group.
Results: Follow-up ranged from 4.0-4.7 years. 24 out of 427 investigated peptide fragments were associated with baseline DR in the discovery set after adjustment for multiple testing. Two of these (COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were also associated to baseline DR in the validation set (Rho: -0.22, p&lt;0.001 and Rho: -0.14, p=0.024). Neither was associated with the development of endpoints. Investigating the discovered fragments in the full cohorts, several collagen fragments were associated with baseline DR and endpoints, in both type 1 and type 2 diabetes, however without overlap.
Conclusions: Several urinary peptide fragments (mainly collagen) were associated with the presence of DR, however, they were not conclusively associated with worsening of DR.

Disclosure
V. Rotbain curovic: None. P. Magalhães: None. T. He: Employee; Self; Mosaiques Diagnostics GmbH. T. W. Hansen: Stock/Shareholder; Self; Novo Nordisk A/S. H. Mischak: Stock/Shareholder; Self; Mosaiques Diagnostics. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd.
432-P: Sodium Intake and Incidence of Diabetes Retinopathy in Elderly Patients with Type 2 Diabetes: Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT)
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , KAMADA CHIEMI , TANAKA SACHIKO , YOSHIMURA YUKIO , KODERA REMI , FUJIHARA KAZUYA , KAWASAKI RYO , MORIYA TATSUMI , SONE HIROHITO , ARAKI ATSUSHI 
Published: June 2021

Though excessive sodium intake is regarded as a crucial factor related to developing and worsening of diabetes complications, data on this topic in elderly patients with diabetes are sparse. We investigated the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65 - 85 years. The present analysis was conducted among Japanese patients with type 2 diabetes from outpatient clinics in 39 university and general hospitals in Japan. Data were analyzed on 912 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to diabetic retinopathy, overt nephropathy, cardiovascular disease, and all-cause mortality during 6 years. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders Mean sodium intake in quartiles ranged from 2498 mg to 5910 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&lt; 2300 mg/day). After adjustment for confounders, HRs for complications in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and complications. Among patients whose vegetable intake was less than the average of 268.7 g, HRs for diabetic retinopathy in patients in the 2nd, 3rd, and 4th quartiles of sodium intake compared with the 1st quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicated that high sodium intake under conditions of low vegetable intake is associated with elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes.

Disclosure
C. Horikawa: None. T. Moriya: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. A. Araki: None. R. Aida: None. S. Tanaka: None. C. Kamada: None. S. Tanaka: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. R. Kawasaki: None.

Funding
Japan Society for the Promotion of Science (19H04028)
434-P: Large Quantity of Alcohol Intake per Occasion was Positively Associated with Vision-Threatening Eye Diseases in Japanese Men with Type 2 Diabetes
Authors: YAMAMOTO MASAHIKO , FUJIHARA KAZUYA , YAGUCHI YUTA , OSAWA TAEKO , KANEKO MASANORI , KITAZAWA MASARU , SATO TAKAAKI , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO 
Published: June 2021

Heavy total alcohol consumption was reported to increase the risk of development and progression of diabetic retinopathy. However, differing from total alcohol consumption, whether the quantity of alcohol intake per occasion had harmful or beneficial effects related to severe eye diseases caused by diabetes remains unknown. To clarify this, we utilized ICD-10 and medical treatment codes from a nationwide claims database that finally included 21,392 men with type 2 diabetes (mean age 53 y, HbA1c 7.0%, mean follow-up period 4.3 y). During the study period, 425 patients developed vision-threatening treatment-required diabetic eye diseases (TRDED) (4.6/1000 person-years). Multivariate Cox analysis demonstrated that a large quantity of alcohol per occasion defined as ≥3 drinks per occasion was positively associated with future occurrence of TRDED. One drink was defined as a standard Japanese drink with a volume equivalent to 23 g ethanol. Hazard ratio in patients drinking large amounts of alcohol per occasion for incident TRDED was 4.49 (95% confidence interval, 1.98-10.19) compared with the reference group (≤1 drink per occasion) after adjusting for covariates including total alcohol consumption. This finding demonstrated that a large quantity of alcohol per occasion had a significant association with future vision-threatening retinopathy in men with type 2 diabetes. The mechanism of this finding with regard to severe retinopathy awaits further research.

Disclosure
M. Yamamoto: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. Y. Yaguchi: None. T. Osawa: None. M. Kaneko: None. M. Kitazawa: None. T. Sato: None. M. H. Yamada: None. Y. Matsubayashi: None.
436-P: Low Prevalence of Diabetic Retinopathy in Type 1 Diabetes Patients with a Long-Term Modernly Treated Disease and Very Good Glycaemic Control: A Retrospective Single-Center Analysis
Authors: SUROWIEC PAULINA , MATEJKO BARTłOMIEJ , KOPKA MARIANNA , FILEMONOWICZ-SKOCZEK AGNIESZKA , KLUPA TOMASZ , ROMANOWSKA-DIXON BOZENA A. , CYGANEK KATARZYNA , MALECKI MACIEJ 
Published: June 2021

Despite continuous progress in the therapy of type 1 diabetes (T1DM), diabetic retinopathy (DR) is still a common chronic complication. We aimed to analyse DR prevalence and its predictors in patients with T1DM lasting 10 years or more, treated with modern methods, and with excellent glycaemic control. The analysis included data from 384 (80.7% women) patients taking part in the Polish National Health Fund’s Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow between 2014-2020. A retrospective analysis of data from medical records was applied. T1DM patients of average 34 ± 9.2 years, mean BMI of 25.0 ± 3.9 and diabetes duration of 20.5 ± 7.9 years was included. The mean HbA1c of all patients throughout the follow-up period was 6.9 ± 1 % [52 mmol/l]. The analysed group consisted of 238 (62,0%) patients treated with CSII, 99 (25.8%) treated with MDI; and 47 (12.2%) who used both methods during the observation period. All patients used short-acting analogues, 144 (98.6%) MDI users were treated with long-acting analogues. DR was confirmed in 150 (39.1%) patients, 109 (72.2 %) of them were diagnosed de novo in the analysed period. Severe DR, defined as an advanced non-proliferative DR or proliferative DR, was observed in 31 persons (8.07% of the entire study group and 20.7% of the DR group).In the multivariate logistic regression model, T1DM duration (OR 1.13; 95% CI, 1.09-1.19), HbA1c level (OR 1.41; 95% CI, 1.08-1.84), LDL level (OR 1.79; 95% CI, 1.16-2.87), and combined incidence of non-DR micro- and macrovascular chronic complications (OR 1.86; 95% CI, 1.16-3.03) were independent risk factors for DR presence. In our long-term retrospective study, the prevalences of both any stage of DR and severe DR were lower than reported in other cohorts from earlier periods. Independent risk factors for DR in this highly selected cohort did not differ from the previously reported.

Disclosure
P. Surowiec: None. B. Matejko: Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care. M. Kopka: None. A. Filemonowicz-skoczek: None. T. Klupa: Advisory Panel; Self; Dexcom, Inc., Ypsomed Group, Employee; Spouse/Partner; Ascensia Diabetes Care, Research Support; Self; Abbott Diabetes, Speaker’s Bureau; Self; Bioton S. A., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi-Aventis. B. A. Romanowska-dixon: None. K. Cyganek: Advisory Panel; Self; Medtronic, Speaker’s Bureau; Self; Lilly Diabetes, Novo Nordisk. M. Malecki: Advisory Panel; Self; Abbott Diabetes, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Mundipharma International, Novo Nordisk, Sanofi-Aventis, Servier Laboratories.
437-P: MicroRNA-223 Expression Is Upregulated in Type 2 Diabetes and Associated with Diabetic Retinopathy in Cohort of Qatar Biobank: Functional Validation in Zebrafish Model
Authors: AKIL AMMIRA S. , DA’AS SAHAR , JERMAN LAILA A. , ABDELRAHMAN DOUA , HASAN WASEEM , FAKHRO KHALID 
Published: June 2021

MicroRNAs (miRNAs/miRs) are implicated in the pathogenesis of type 2 diabetes (T2D) and its long-term complications such as retinopathy. miRNAs circulating levels have explored as possible biomarkers for the advancement of T2D. We examined the expression of customized set of miRNAs in T2D Qatari nationals with and without diabetic retinopathy (DR) from Qatar Biobank 1000 Qatar omics cohort. MiR-223 appeared to be significantly upregulated in T2D in comparison to the healthy controls. MiR-223 previously found to play a role in insulin resistant human adipose tissues, human and murine obesity and potential regulators of optic nerve regeneration. To further investigate the potential role of miR-223 in the development of DR, we established a zebrafish (ZF) model to functionally validate this potential correlation. Our aim is to investigate the miR-223 with hyperglycemia on the developing retina in the ZF as a vertebrate model. Mimic miR-223 was injected into single cell ZF embryos and incubated in normal and induced hyperglycemia conditions. We have examined the glucose ratios, eye morphology and vasculature structure in the developing model in comparison to the control groups. To understand the cellular mechanisms involved in DR; histological examination, cell apoptosis and proliferation have been performed and to be evaluated. miR-223 over expression resulted in an alteration of the glucose metabolism within the ZF model. Glucose ratio was significantly increased in ZF embryos injected with mimic miR-223. Increased miR-223 in the developing ZF larvae together with hyperglycemia affected the retinal development. The eye size was significantly reduced with degenerated vasculature and altered eye morphology.
In conclusion, we have identified a novel correlation between DR development and miR-223. Targeting miR-223 in T2D patients may serve as promising therapeutic strategy to control DR in at risk T2D patients.

Disclosure
A. S. Akil: None. S. Da’as: None. L. A. Jerman: None. D. Abdelrahman: None. W. Hasan: None. K. Fakhro: None.

Funding
Qatar National Research Fund (NPRP9-229-3-041)
438-P: Contribution of Hypertriglyceridemia to Cardiovascular Disease in Korean Women: A Nationwide Population-Based Study
Authors: CHOE HUN JEE , MOON MIN KYONG , KOO BO KYUNG 
Published: June 2021

Introduction: The independent effect of serum triglyceride (TG) level on the development of cardiovascular disease (CVD) has been inconclusive, which might be due to heterogeneity of study populations. We aimed to evaluate the effect of TG level on CVD and mortality in Korean women with stratification according to the menopausal status, diabetes mellitus (DM) or LDL cholesterol level (LDL-C).
Method: We investigated Korean women aged 40-69 years who underwent health examination in 2009 and were followed up until 2018 using nationwide claim data covering 97.0% of the Korean population. The subjects were divided into four groups according to TG quartiles (Q): Q1 &lt;70 mg/dL, Q2 71-99 mg/dL, Q3 100-142 mg/dL, Q4 ≥143 mg/dL. The primary outcome was the incidence of CVD defined as composite of myocardial infarction and ischemic stroke.
Results: Among 2,208,347 women, primary outcome occurred in 62,255 (2.8%) subjects. As TG levels increased, the event rate of primary outcome increased in both premenopausal and postmenopausal women in the fully adjusted model (hazard ration [HR] per 1 Q, 1.10 [95% confidence interval (CI), 1.08-1.12] and 1.08 [95% CI, 1.07-1.09], respectively), which was maintained on further stratification according to DM or LDL-C (p&lt;0.05 in all). In premenopausal women without diabetes and LDL-C of less than 130 mg/dL, even those in Q2 had a significantly higher CVD risk compared to subjects in Q1 (p&lt;0.05), which was not found in the in subjects with diabetes or in the higher range of LDL-C.
Conclusion: TG is an independent prognosticator in the development of CVD in the Korean women aged 40-69 years. The dose-response relationship is more significant in patients without diabetes when LDL-C&lt;130mg/dL. These results imply that more emphasis should be set on TG when assessing women with elevated TG levels with otherwise few established risk factors.

Disclosure
H. Choe: None. M. Moon: None. B. Koo: None.
44-LB: Insulin Treatment Satisfaction Questionnaire Results for PRONTO-Pump-2 Study
Authors: PIRAS DE OLIVEIRA CAROLINA , PACZKOWSKI ROSIRENE , CHO JANG IK , JUNEJA RATTAN , POON JIAT LING , HANKOSKY EMILY R. , IGNAUT DEBRA A. 
Published: June 2021

Background: In PRONTO-Pump-2, a Phase 3, 16-week, randomized, double-blind clinical trial in patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII), ultra rapid lispro (URLi; a novel mealtime insulin), showed superior postprandial glucose control and noninferior HbA1c reduction, with less hypoglycemia compared to Humalog® (Lispro). We assessed treatment satisfaction in patients enrolled in this trial (URLi, N=215; Humalog, N=217), using the Insulin Treatment Satisfaction Questionnaire (ITSQ).
Methods: The ITSQ was administered to patients at baseline and endpoint (week 16 or early discontinuation). The 5 domains assessed were glycemic control, hypoglycemic control, insulin delivery device, inconvenience of regimen, and lifestyle flexibility. Domain scores were transformed to a scale of 0-100 for analysis, with higher scores indicating better treatment satisfaction. The change in each domain-specific and overall transformed score from baseline to endpoint (last observation carried forward) was analyzed using an ANCOVA model.
Results: At endpoint, for patients treated with URLi, glycemic control scores had increased from a baseline of 66.9 by +7.0 (standard error [SE] 1.59; p&lt;0.001), and scores for all other domains, except hypoglycemic control, had numerically increased. For patients treated with Humalog, glycemic control scores increased from a baseline of 61.3 by +3.9 (SE 1.51; p=0.010) while inconvenience of regimen scores decreased from a baseline of 80.0 by -2.5 (SE 1.13; p=0.029). At endpoint, the inconvenience of regimen score was significantly higher with URLi treatment compared to Humalog (between-treatment difference: 2.9 [95% CI 0.2, 5.6]; p= 0.034). No significant differences were observed in the overall ITSQ score between treatments.
Conclusion: Patients with type 1 diabetes treated with URLi using CSII reported to be satisfied with the glycemic control they experienced and perceived URLi treatment to be more convenient than Humalog.

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

Funding
Eli Lilly and Company