bluuebunny/crossref_metadata_2025_split huggingface dataset:
42-PUB: Income-Related Inequalities in Self-Reported Vision Problems among U.S. Adults, 1999–2018
Authors: CHEN YU , KIM MINCHUL , LUNDEEN ELIZABETH A. , ROLKA DEBORAH B. , EHRLICH JOSHUA R. , ANNE NEWMAN-CASEY PAULA , ELAM ANGELA , REIN DAVID B. , HOLLIDAY CHRISTOPHER S. , SAADDINE JINAN B. 
Published: June 2024

Introduction & Objective: Research has shown that the prevalence of vision problems is higher among U.S. adults with low income. Recent changes in income-related inequalities (IRI) in the prevalence of vision problems are unknown. We aim to examine trends in IRI in vision problems and to identify the relative contribution of determining factors.
Methods: We estimated annual IRI in vision problems in 1999−2018 among US adults aged ≥18 years using data from the National Health Interview Survey. Vision problems are defined as an affirmative response to the question: “Do you have trouble seeing, even when wearing glasses or contact lenses?”. We used the concentration index (CI) to measure IRI and quantified the extent to which the prevalence of vision problems concentrates in lower income versus higher income groups. We used the Wagstaff decomposition method to decompose CI into contributors. We examined trends from 1999−2018 in vision problems inequality and contributors to those trends over time.
Results: Between 1999−2018, the CIs were below 0, signifying that vision problems were more concentrated among individuals with lower incomes. The degree of IRI in vision problems increased from 1999−2018 (annual percent change=0.6, p=0.03). IRI in vision problems was greater among adults aged 45-64 years than other age groups. Decomposition analysis revealed that poverty-to-income ratio and public health insurance coverage were the largest contributors to IRI in vision problems, with smaller contributions made by smoking, physical inactivity, and female sex. Among all variables, non-White race/ethnicity, lower physical activity, and poverty-to-income ratio were the main factors explaining trends in vision problems inequality over time.
Conclusion: Self-reported vision problems were more prevalent in low-income populations, and IRI widened over time. The sustained growth in income inequality may lead to a larger population burden of vision problems.

Disclosure
Y. Chen: None. M. Kim: None. E.A. Lundeen: None. D.B. Rolka: None. J.R. Ehrlich: None. P. Newman-Casey: None. A. Elam: None. D.B. Rein: None. C.S. Holliday: None. J.B. Saaddine: None.
426-P: Association of Succinate and Adenosine Nucleotide Metabolic Pathways with the Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
Authors: JUNG INHA , NAM SEUNGYOON , PARK SOYOUNG , YOUNG LEE DA , HEE YU JI , A SEO JI , HO LEE DAE , HEE KIM NAN 
Published: June 2024

Introduction & Objective: The prevalence of diabetic kidney disease (DKD) is increasing, and biomarkers that can enhance prognosis beyond renal function and albuminuria are rare. This study aimed to evaluate the potential of adenosine, succinate, and their related pathways, including hyaluronic acid (HA), as predictors of DKD progression.
Methods: We examined 230 participants categorized as healthy controls, DKD non-progressors, and rapid progressors. Eligible patients with diabetes had at least five prior urine creatinine measurements during a median of 5.8 years of follow-up. Using previously collected eGFR data, rapid progressors were identified based on a decline in eGFR (ΔeGFR/year ≤−3 mL/min/1.73 m2/year or annual rate of eGFR decline ≥ 3.3%) before enrollment. At the end of the cohort, we measured the concentrations of urinary adenosine, succinate, HA, and serum cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation. Associations between eGFR, ΔeGFR, and albuminuria were analyzed after adjusting for DKD progression risk factors.
Results: Urinary succinate and serum CD39 levels were more elevated in rapid progressors compared to controls and non-progressors. This trend persisted when using the percentage criterion (≥40% decline in eGFR) for renal disease progression. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR at enrollment, ΔeGFR and albuminuria. However, among the various metabolites studied, multivariate regression analysis identified urinary succinate as an independent metabolite of rapid DKD progression and albuminuria.
Conclusion: Among several potential metabolites, only urinary succinate exhibited associations with rapid DKD progression.

Disclosure
I. Jung: None. S. Nam: Consultant; HieraBio Inc., Korea, Republic of. S. Park: None. D. Lee: None. J. Yu: None. J. Seo: None. D. Lee: None. N. Kim: None.

Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2023R1A2C2003479) and the Bio & Medical Technology Development Program of the NRF funded by MSIT (NRF-2019M3E5D3073102). This study was also supported by a National IT Industry Promotion Agency (NIPA) grant funded by the MSIT (No. S0252-21-1001, Development of AI Precision Medical Solution (Doctor Answer 2.0)) and a Korea Health Industry Development Institute (KHIDI) grant funded by the Ministry of Health & Welfare of Korea (No. HI16C1997 and No. HI23C0679).
431-P: Identification of the Serum Uric Acid Threshold for Predicting Diabetic Nephropathy Risk in Patients with Type 1 Diabetes
Authors: ZHANG MEI , HUANG MEI , WEI QIANYING , CHEN XIN , WANG SUYU , QIN YAO , DAI LIUYAN , YANG TAO 
Published: June 2024

Introduction & Objective: To clarify the correlation between SUA levels and the risk of DN in Chinese patients with T1DM, and determine the SUA threshold associated with an increased risk of DN.
Methods: Both cross-sectional study and longitudinal study were conducted. The cross-sectional study was conducted with 681 subjects with T1DM. Adjusted multivariable logistic regression analysis was used to investigate the association between SUA levels and the risk of developing DN in patients with T1DM. Restricted cubic spline (RCS) was applied to determine the optimal threshold for SUA. Longitudinal data were collected from 94 patients with at least 3 visits to evaluate the variability of SUA levels with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR).
Results: The 681 patients were divided into four groups based on the quartile SUA levels. The median SUA level was 4.18mg/dL. Among 681 participants in this analysis, median age was 42 (IQR 28-55) years and 52.4% were male, the incidence of DN was 12.6%. After adjusting for confounding factors, the SUA level was inversely significantly correlated with the risk of DN (OR 1.57 [95% confidence interval (CI) 1.26; 1.95], P&lt;0.001). The RCS plot revealed a U-shaped relationship between SUA levels and DN, with the identified threshold of SUA being 3.85mg/dL in female and 4.64mg/dL in male (Figure 1). Correlation analysis showed the SUA variability was significantly correlate with eGFR variability (r=0.206, p=0.046) and UACR variability(r=0.405, p&lt;0.01) (Figure 2).
Conclusion: Our study identified SUA as a significant risk factor for DN in Chinese T1DM patients and established the optimal threshold with 3.85mg/dL in female and 4.64mg/dL in male for predicting DN risk. Our findings provide important evidence for improving risk discrimination and reclassification of high-risk DN subjects in clinical practice.

Disclosure
M. Zhang: None. M. Huang: None. Q. Wei: None. X. Chen: None. S. Wang: None. Y. Qin: None. L. Dai: None. T. Yang: None.
439-P: Beat-to-Beat Blood Pressure Variability, Linkage with Sudden, High Blood Pressure Elevations, Implications to Treat Labile Arterial Hypertension in Diabetes
Authors: GMITROV JURAJ 
Published: June 2024

The goal was to estimate the link between blood pressure (BP) variability (BPV) and catecholamine BP surges. Mean femoral arterial BP (MAP), heart rate (HR) and ear lobe skin microcirculatory blood flow, by microphotoelectric plethysmography (MPPG), were recorded in conscious rabbits after 40 min carotid baroreceptor (CB) exposure to 350 mT static magnetic field (SMF), induced by Nd2-Fe14-B (n = 14) or sham magnets (n = 14), Fig. 1. Arterial baroreflex sensitivity (BRS) was estimated by HR and MAP responses to i.v. bolus inj. of phenylephrine (Ph) and nitroprusside (Ni), beat-to-beat BPV by MAP standard deviation (SD). SMF CB exposure significantly increased BRSNi (74.5 ± 17.8%, P &lt; 0.001) and microcirculation (23.8% ± 11.0%, P = 0.039); decreased MAP (−5.7 ± 1.7%, P &lt; 0.014), and Ph-induced MAP surge (−19.1%, P = 0.043), which is positively correlated with resting MAP (r = 0.342, P = 0.0383) and MAP SD (r = 0.383, P = 0.0194), and inversely with BRSPh (r = −0.47, P = 0.0156). CB magnetic stimulation increased Ni vasodilator effect, which acts as a nitric oxide (NO) donor, suggesting baroreflex to improve vessels sensitivity to NO-mediated dilation (impaired in diabetes), being a new physiology with BP buffering result. Enhanced BPV suggested to be a diagnostic tool for diabetics' susceptibility to morning surges of BP linked with major macrovascular events.

Disclosure
J. Gmitrov: None.
445-P: Waist–to–Body-Mass-Index Ratio Predicts Cardiovascular Events in Patients with Cardiovascular Disease Independently of Type 2 Diabetes
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

Waist circumference reflects central fat accumulation and is an important additive information to BMI. The Waist Circumference-to-Body-Mass-Ratio (W/BMI-Ratio) has been suggested to provide additional information on cardiovascular event risk. Its power to predict cardiovascular events in patients with established cardiovascular disease is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in 1200 patients with angiographically verified coronary artery disease (n=938) or sonographically proven peripheral artery disease. The mean follow-up time was 10.4±5.0 years. At baseline, there was no significant difference in the W/BMI-Ratio between patients with (n=422) and those without T2DM (3.6±0.4 vs. 3.6±0.3; p=0.442). Prospectively, the W/BMI-Ratio significantly predicted the incidence of cardiovascular events (n=642) both univariately (standardized HR 1.14 [1.07-1.22], p&lt;0.001) and after adjustment for age, gender, smoking, LDL cholesterol, HDL cholesterol, hypertension and T2DM (standardized adjusted HR=1.15 [1.07-1.23], p&lt;0.001); HRs were 1.12 [1.02±1.22], p=0.014 in patients without diabetes and 1.23 [1.09-1.38], p&lt;0.001 in those with T2DM, with a non-significant interaction W/BMI-Ratio x diabetes status (p=0.159). We conclude that the W/BMI-Ratio independently from diabetes status is a predictor for cardiovascular events in patients with established cardiovascular disease.

Disclosure
T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
470-P: Severe Liver Fibrosis (F4) Assessed via Liver Fibroscan Is Associated with Elevated NT-ProBNP in Asymptomatic Type 2 Diabetes Mellitus Patients Receiving SGLT2i Therapy
Authors: GUPTA VISHAL 
Published: June 2024

Aim: Identify relationship between different stages of liver fibrosis (LF) & N-terminal pro-B type natriuretic peptide (NT-ProBNP).
Methods: Between Oct’ 22 & Mar’ 23, 66 T2DM patients receiving dapagliflozin & waist cmf &gt; 80 cms (F) & &gt; 90 cms (M) irrespective of their A1c & who underwent Liver Fibroscan (Lfib) were retrospectively analysed & studied. Metavir stg classified patients: F0 (N); F1 (N - mild); F2 (Mild - mod); F3 (mod - severe); F4 (cirrhosis). LF was assessed by Lfib performed using ARFI. Exclusion: pregnancy, &lt;3 mnth illness, hospitalisation, H/O heart disease, alcoholism & hep B, C & autoimmune hepatitis (if raised LFT). Weight-kg (W), systolic/diastolic BP (mmHg), Lipid profile mg/dl (TC, LDL, TG, HDL), LFT, Hs-CRP mg/L, NT-ProBNP pg/ml, eGFR (Cr & Cyst-C) & UACR were recorded every 2-3 mnths & data presented over 1 yr.
Statistics: ANOVA - compared means between 3 data points & stgs of LF. One-Way ANOVA followed by post-hoc Tukey test compared NT-ProBNP to LF stages & P value &lt;0.05 was considered statistically significant (S). Baseline (B) characters: Males 86.4%, avg (age 56.88&lt;u&gt;+&lt;/u&gt;8.82, W 83.72&lt;u&gt;+&lt;/u&gt;11.96, SBP 134.79&lt;u&gt;+&lt;/u&gt;17.46, DBP 86.61&lt;u&gt;+&lt;/u&gt;11.94, A1c 7.77&lt;u&gt;+&lt;/u&gt;1.54, TC 153.72&lt;u&gt;+&lt;/u&gt; 46.18, LDL 86.76&lt;u&gt;+&lt;/u&gt;40.29, HDL 38.86&lt;u&gt;+&lt;/u&gt;8.08, TG 164.16&lt;u&gt;+&lt;/u&gt;90.82, hs-CRP 2.57&lt;u&gt;+&lt;/u&gt;2.83, GGT 49&lt;u&gt;+&lt;/u&gt;51.96, SGPT 40.44&lt;u&gt;+&lt;/u&gt;25.89, NT-ProBNP 46.65&lt;u&gt;+&lt;/u&gt;45.71, UACR 33.43&lt;u&gt;+&lt;/u&gt;99.55 & eGFRCys-C 84.98&lt;u&gt;+&lt;/u&gt;20.55). (B) - 1 yr: S reduction seen in Wt, DBP, A1c, TC, LDL, TG, hs-CRP & SGPT. S relation was seen with stage F4 LF & NT-ProBNP (123.36&lt;u&gt;+&lt;/u&gt;124.01, p-0.049) but not with other stages of LF (F0 49.67&lt;u&gt;+&lt;/u&gt;42.57, F1 54.40&lt;u&gt;+&lt;/u&gt;34.64, F2 17.66&lt;u&gt;+&lt;/u&gt;10.38, F3 27.35&lt;u&gt;+&lt;/u&gt;10.96) at the end of the study. There was no S association seen between liver enzymes & NT-ProBNP at any LF stg.
Conclusion: Severe liver fibrosis (F4) is associated with elevated NT-ProBNP in Indian patients with T2DM compared to other stages of LF despite receiving SGLT2i therapy. Further cardiac evaluation may be warranted in this population.

Disclosure
V. Gupta: None.
479-P: Imeglimin Improves Hyperglycemia-Induced Mitochondrial Dysfunction and Increases SIRT1 and NAD+ Biosynthesis in Schwann Cells
Authors: KATO AYAKO , NIHEI WATARU , YAKO HIDEJI , SANGO KAZUNORI , NAKAMURA NOBUHISA , NARUSE KEIKO , HIMENO TATSUHITO , KATO YOSHIRO , NAKAMURA JIRO , KAMIYA HIDEKI , KATO KOICHI 
Published: June 2024

Hyperglycemia-induced oxidative stress is a major cause of the pathogenesis of diabetic neuropathy, and hyperglycemia-induced mitochondrial ROS production is considered as a significant mechanism of increased oxidative stress. On the other hand, imeglimin is the first in a new glimin class of anti-diabetic drugs targeting mitochondrial bioenergetics. In addition, imeglimin has been reported to enhance insulin secretion by increasing nicotinamide adenine dinucleotide (NAD+) levels in rat islets via the salvage pathway involving nicotinamide phosphoribosyltransferase (NAMPT). Moreover, NAD+ has been shown to modulate sirtuin and PGC1α, which in turn ameliorate mitochondrial dysfunction. We investigated the effects of imeglimin on high glucose-induced cell death and mitochondrial dysfunction in Schwann cells. In addition, the effects of imeglimin on NAD+ levels, NAMPT activity, the rate-limiting enzyme in the salvage pathway for NAD+ synthesis, and SIRT1 expression, a longevity gene, were evaluated. Immortalized adult mouse Schwann (IMS32) cells were cultured in 5.5 mM normal glucose (NG) and 25 mM high glucose (HG) medium. Compared to NG, HG decreased cell viability and increased mitochondrial oxidative stress. HG decreased mitochondrial membrane potential, increased mitochondrial oxygen consumption rate (OCR), increased activity of complex I and decreased ATP levels. Imeglimin ameliorated the reduction in cell viability and improved these mitochondrial dysfunctions. In addition, imeglimin increased NAMPT activity and NAD+ levels in IMS32 cells under HG conditions. Furthermore, imeglimin also ameliorated the reduction in SIRT1 expression by HG. These results suggest that imeglimin may prevent diabetic neuropathy by attenuating hyperglycemia-induced mitochondrial dysfunction and cell death in Schwann cells, at least in part, through the enhancement of SIRT1 and NAD+ biosynthesis.

Disclosure
A. Kato: None. W. Nihei: None. H. Yako: None. K. Sango: None. N. Nakamura: None. K. Naruse: None. T. Himeno: None. Y. Kato: None. J. Nakamura: None. H. Kamiya: Speaker's Bureau; Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Boehringer-Ingelheim, Daiichi Sankyo, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Novartis Pharmaceuticals Corporation, Merck & Co., Inc., Sanwa Kagaku, Otsuka Pharmaceuticals Corporation. Research Support; Kissei Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly and Company, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Japan Tobacco Inc, Novo Nordisk. Speaker's Bureau; Taiho Pharmaceutical Co. Ltd., Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Teijin Pharma Limited, Bayer Inc. K. Kato: None.
483-P: Understanding the Macrostructural Foundations of Nerve Dysfunction in Diabetic Neuropathy
Authors: FLEMING THOMAS H. , KENDER ZOLTAN , SZENDROEDI JULIA 
Published: June 2024

Background & Objectives: Focal fascicular lesions have been identified in the sciatic nerves of individuals with diabetic neuropathy (DN). The presence of these lesions, which occurs in proximal-to-distal gradient, closely correlates with the severity of clinical symptoms. The objective of this study was to understand the structural nature of the fascicular lesions and gain insights into their pathophysiology.
Methods: A combinational approach of ex vivo magnetic resonance neurography (MRN) and in vitro imaging was used to identify, isolate, and analyze the structural nature of fascicular lesions from the sciatic nerves of individuals with and without type-2 diabetes (T2D). Comparative spatial proteomic analysis was then used to decipher the molecular composition of the lesions.
Results: Three fascicle types were identified: normal appearing fascicles (NAF-Ctrl), T2D-fascicles (NAF-T2D), and T2D-fascicles with lesions (T2D lesions). The T2D lesions, identified as hypertensive based on MRN signals, showed distinct differences from other fascicles—increased area, perineurium loss, accumulation of acid mucin, and reduced myelinated axons, suggesting endoneurial edema. 346 proteins were common across all types, with significant variations between NAF-Ctrl and T2D lesions. Notably, T2D lesions exhibited reduced neuroprotective pathways, such as such as protein kinase A, the pentose-phosphate pathway, and aldo-keto reductase/aldehyde dehydrogenase metabolism and activation of pathways linked to liver-derived autoantibody complement activation.
Conclusion: The combination of MRN imaging with histological analysis, had led to a deeper understanding of structural nature of fascicular lesions. The incorporation of spatial proteomics has furthered insights into lesion pathophysiology, unveiling potential therapeutic treatment strategies for this complex condition.

Disclosure
T.H. Fleming: None. Z. Kender: None. J. Szendroedi: None.

Funding
Deutsche Forschungsgemeinschaft (DFG; SFB1118 and SFB1158); the German Center for Diabetes Research (DZD)
490-P: Ongoing Treatments with High Concentration Capsaicin Topical System Results in Progressive Pain Reduction for Painful Diabetic Neuropathy—A Retrospective Real-World Analysis
Authors: GRAF GARY , ALLEN SAMUEL , CARNEVALE AUDREY 
Published: June 2024

The capsaicin 8% topical system is FDA-approved for the treatment of pain associated with diabetic neuropathy (PDPN) of the feet and post-herpetic neuralgia. The hypothesis that patients experience a progressive response with ongoing treatments was the purpose of this analysis. Eighteen patients who received at least 3 treatments were selected, some patients were not analyzed due to missing data. Efficacy was measured using a pain rating scale from 0-10. Initial pain level was taken before administering capsaicin 8%, with follow-up scores measured during an evaluation between treatments. Most patients had a 50% or greater reduction in pain, with fifteen responding on the first treatment, one on the second treatment, and two non-responders. Patients experienced an acute reduction in average pain intensity following each application, with an additive reduction in pre-treatment pain scores prior to the second and third applications (Figure 1). Capsaicin 8% induces analgesia by lysing aberrant nociceptive fibers. The regeneration of these nociceptors is associated with pain recurrence due to the continual consequence of diabetes. These data are consistent with previous studies and may signify a more normal nerve fiber regrowth in PDPN patients, suggesting the need for ongoing treatments to maintain this progressive response.

Disclosure
G. Graf: Consultant; Averitas Pharma, Inc. Speaker's Bureau; Averitas Pharma, Inc. S. Allen: Employee; Averitas Pharma, Inc., Lundbeck. A. Carnevale: Employee; Averitas Pharma, Inc.
495-P: Diabetic Retinopathy Is a Ceramidopathy Reversible by Systemic Anticeramide Therapy
Authors: BUSIK JULIA V. , DORWEILER TIM F. , SINGH ARJUN , GRANT MARIA B. , KOLESNICK RICHARD 
Published: June 2024

Introduction: Diabetic retinopathy (DR) is characterized by retinal endothelial cell (REC) death and inadequate vascular repair by dysfunctional circulating angiogenic cells (CACs). We have previously demonstrated an increase in ASM-mediated C16 ceramide and ceramide-rich platform (CRP) formation as a major pathogenic mechanism in the development of REC damage and CAC dysfunction in DR. Using anti-ceramide Abs, we aimed to prevent REC damage and restore CAC-mediated repair by dispersing CRPs, thus restoring retinal microvascular health and preventing DR.
Methods: Anti-ceramide Abs were administered in vitro or ex vivo at 10 (short chain fragment antibody; scFv) /100 (monoclonal antibody; mAb) μg/mL and in vivo (subcutaneously) at 60μg/g (mAb) bodyweight in STZ induced diabetic mouse model. Migration of CACs was assessed using trans-well assays ex vivo. In vivo vascular degeneration was captured using FITC-albumin technique. In vivo migration of GFP+ CACs (JAX:006567) was examined via confocal imaging.
Results: In vitro studies in BRECs show generation of vast ceramide rich platforms followed by apoptosis upon acute stimulation with 20ng/mL TNFa or 10ng/mL IL-1β. This phenotype was fully ameliorated when treated with anti-ceramide scFv. STZ mice showed a significant increase (42% CRP pos. cells) in CRP formation on day 3, with gradual increases on day 7, 14, 42, and 180 (70% pos.) post-hyperglycemia (n=9-12, p&lt;0.0001. Anti-ceramide treatment reduced CRP formation on CACs and protected from retinal vascular permeability 6-weeks post hyperglycemia in vivo (n=10-12; p&lt;0.01. In vivo migration and vascular repair of CACs was impaired in 6-month diabetic STZ mice compared to their age matched controls and rescued following anti-ceramide Abs intervention (scFv and mAb) in vivo (n=4-7; p&lt;0.08).
Conclusion: Anti-ceramide Abs restore microvascular health via normalization of both REC and CACs homeostasis to halt or reverse DR.

Disclosure
J.V. Busik: Consultant; Ceramedix, Inc. T.F. Dorweiler: None. A. Singh: None. M.B. Grant: None. R. Kolesnick: Stock/Shareholder; Ceramedix Holding LLC.

Funding
R01EY030766R01EY025383R01EY016077