bluuebunny/crossref_metadata_2025_split huggingface dataset:
433-P: Syndecan-1, a Marker of Endothelial Glycocalyx Degradation, Is Associated with Albuminuria in Type 2 Diabetes
Authors: KAKUTANI YOSHINORI , MORIOKA TOMOAKI , YAMAZAKI YUKO , OCHI AKINOBU , FUKUMOTO SHINYA , SHOJI TETSUO , EMOTO MASANORI 
Published: June 2023

The endothelial glycocalyx (EG) covers the luminal surface of vascular endothelium and is involved in various functions of endothelium including the microvascular permeability. Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of EG. Since the extracellular domain of SDC-1 is shed by inflammatory mediators, increased circulating levels of SDC-1 is considered as a marker of EG degradation. No study has thus far investigated the relationship between EG degradation and albuminuria in type 2 diabetes. This study aimed to investigate the association between EG degradation assessed by serum SDC-1 levels and urinary albumin to creatinine ratio (ACR) in type 2 diabetes. This study enrolled 370 Japanese patients with type 2 diabetes (T2D) and 219 nondiabetic controls (ND). Patients with severe kidney dysfunction whose estimate glomerular filtration rate (eGFR) was less than 30 mL/min/1.73m2 were excluded. T2D patients were divided into normoalbuminuria (A1), microalbuminuria (A2) and macroalbuminuria (A3) by ACR. Median value of serum SDC-1 levels in T2D with A1 stage was 24.5 ng/mL which was higher than that in ND (16.0 ng/mL) (p &lt;0.001). Median values of SDC-1 in T2D with A2 and A3 stages were 29.0 and 38.7 ng/mL, respectively, which were significantly different among albuminuria stages (p &lt;0.001). First, multivariate analysis including T2D patients with A1 stage and ND revealed that the presence of T2D was independently associated with serum SDC-1 level (β = 0.356, p &lt;0.001). Next, multivariate analysis in T2D patients with all albuminuria stages revealed that serum SDC-1 level was independently associated with ACR (β = 0.121, p = 0.012) after adjustment for known other risk factors for albuminuria. In conclusion, serum SDC-1 level is increased in T2D compared to ND and is an independent determinant of ACR in T2D patients. This study suggests a potential involvement of the EG degradation in albuminuria in T2D.

Disclosure
Y. Kakutani: None. T. Morioka: None. Y. Yamazaki: None. A. Ochi: None. S. Fukumoto: None. T. Shoji: Research Support; Ono Pharmaceutical Co., Ltd., Bayer Inc. Other Relationship; Kowa Company, Ltd. M. Emoto: None.
437-P: Establishing a Simple Decision-Making Model for the Differential Diagnosis of Diabetes Kidney Disease and Nondiabetes Kidney Disease in T2D Patients through Machine Learning
Authors: ZHANG LIN 
Published: June 2023

Objective: To study the 2-DM patients with renal biopsy, analyze the risk factors of DKD and establish a simple decision model to differentiate DKD and NDKD.
Methods: 99 2-DM patients were admitted to hospital in Beijing from December 1, 2018 to December 31, 2021. All of the patients accepted kidney biopsy and biochemical test, fundus photography and OCTA. According to the pathological reports, 99 cases were divided into DKD group and NDKD group. The difference indicators of the two groups were compared. The risk factors of DKD were analyzed by logistic regression. A simple and convenient method to distinguish DKD and NDKD was established through the decision tree model.
Results: This study was a cross-sectional study. Compared with DKD and NDKD groups, the ratio of male/female in DKD group was higher than that in NDKD group (P=0.033), DR prevalence rate was significantly higher than that in NDKD group (P&lt;0.001), course DM, FBG, HBAIC, SBP, TC and EGFR were also higher than those in NDKD group, and HGB decreased. Binary logistic regression analysis was conducted to determine whether DKD was combined. After adjusting for the above indicators, age, DR, course of DM, HBA1C and HGB were still independently related to DKD. A decision tree model was established with the training set: the course DM, DR, and HBA1C were risk factors of DKD. The accuracy of prediction classification is 75%, the sensitivity was 46.2%, and the specificity was 88.9%.
Conclusion: If the patients with type 2 diabetes kidney injury have poor blood glucose control, no DR but anemia, a renal puncture should be considered for definite diagnosis of NDKD.

Disclosure
L.Zhang: None.

Funding
Beijing Science & Technology Development of Traditional Chinese Medicine (JJ-2020-25)
44-OR: Structural Racism and Prevalence of Diabetes in a Nationally Representative Sample of U.S. Adults
Authors: EGEDE LEONARD E. , WALKER REBEKAH J. , CAMPBELL JENNIFER A. , LINDE SEBASTIAN 
Published: June 2023

Background: Prior research has established that historic redlining is a reliable indicator of structural racism. The goal of this study was to investigate the direct and indirect relationships between historic redlining and prevalence of diabetes in a national sample.
Methods: Using a previously validated conceptual model, we hypothesized pathways between structural racism and prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing instability, education, and unemployment. We combined census tract level data including diabetes prevalence from the CDC PLACES 2019 database, redlining using historic Home Owners’ Loan Corporation (HOLC) maps from the Mapping Inequality project, and census tract data from the Opportunity Insights database. HOLC grade (a score between 1=best and 4=redlined) for each census tract was based on overlap with historically HOLC graded areas. The final analytic sample consisted of 9,590 US census tracts. Structural equation modeling was used to investigate direct and indirect relationships adjusting for 2010 population.
Results: Higher prevalence of diabetes was directly associated with increased redlining (B=0.28, p&lt;0.001). Redlining was directly associated with incarceration (B=0.25, p&lt;0.001); poverty (B=-0.28, p&lt;0.001); housing instability (B=-0.09, p&lt;0.001)); education (B=-0.32, p&lt;0.001); and unemployment (B=-0.34, p&lt;0.001). Redlining was indirectly associated with prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing instability, education, and unemployment with strongest associations for discrimination (B=0.32, p&lt;0.001); binge drinking (B=-0.62, p&lt;0.001) and smoking (B=0.39, p&lt;0.001).
Conclusions: Redlining has significant direct and indirect relationships with diabetes prevalence. Discrimination and substance use may be important targets for interventions aiming to mitigate the impact of structural racism on diabetes.

Disclosure
L.E.Egede: None. R.J.Walker: None. J.A.Campbell: None. S.Linde: None.

Funding
National Institutes of Health (R01DK118038, R01DK120861, R01MD013826, K01DK131319)
441-P: Long-Term Effects of Intensive Lifestyle Intervention in Real-World Clinical Practice on Cardiometabolic Outcomes in Patients with Diabetes—A 15-Year Longitudinal Study
Authors: KHATER ABDELRAHMAN , AL-BADRI MARWA , SALAH TAREQ , DHAVER SHILTON E. , KIBAA KARIM , MCCARRAGHER RYAN , HAMDY OSAMA 
Published: June 2023

We previously demonstrated that achieving and maintaining ≥7% weight loss at one year in patients with diabetes (DM), through multidisciplinary intensive lifestyle intervention (ILI) in real-world clinical practice, predicts improvement in cardiometabolic outcomes at 5 and 10 years. In this prospective follow-up, we report 15-year results. We evaluated 122 patients with DM and obesity (mean age 53.2±10.0 years, 68% females, 90.2% type 2, mean DM duration 9.1±8.6 years, mean BMI 38.4±5.2 kg/m²) who underwent 12 weeks of ILI. The total cohort lost in average 10.7±4.6 kg (-9.6%, p&lt;0.001) after 12 weeks. At 1 year, they were divided into group A, who maintained &lt;7% weight loss (47.5%), and group B, who maintained ≥7% weight loss (52.5%). At 15 years, average weight loss in the entire cohort was 8.6±11.9 Kg (-7.6%, p&lt;0.001). Group A maintained an average weight loss of 3.9±6.5 kg (-3.6%) at 5 years, 3.8±9.4 kg (-3.9%) at 10 years and 3.8±10.0 kg (-4.0%) at 15 years. Group B maintained an average weight loss of 10.6±9.8 kg (-9.1%) at 5 years, 10.8±9.6 kg (-9.3%) at 10 years and 12.9±12.0 Kg (-11.0%) at 15 years. At 15 years, weight loss in group B remained significantly higher than in group A (p&lt;0.001). In group A, A1C reduced from 7.5±1.4% to 6.7±0.9% at 12 weeks, but rebounded to 8.0±1.9% at 5 years and 10 years and was 7.9±1.8% at 15 years. In group B, A1C decreased from 7.3±1.1% to 6.3±0.8% at 12 weeks, and was 7.4±1.6% at 5 years, 7.2±1.4% at 10 years and 7.3±1.5% at 15 years (p=0.04 between groups). Both groups maintained significant improvements in LDL- and HDL-cholesterol at 15 years, but group A had significant worsening of their serum triglycerides. Both groups had nonsignificant changes in blood pressure at 15 years. In conclusion, ILI in real-world clinical practice that results in ≥7% weight loss at one year in patients with DM and obesity is associated with continued improvement in cardiometabolic outcomes at 15 years.

Disclosure
A.Khater: None. M.Al-badri: None. T.Salah: None. S.E.Dhaver: None. K.Kibaa: None. R.Mccarragher: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation.
444-P: Satisfaction with Information Regarding Pharmaceutic Therapy in Angiographied Coronary Patients with Type 2 Diabetes
Authors: RATZ MAGDALENA , VOGEL JOHANNES , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2023

Satisfaction with information regarding pharmaceutic therapy is important because it may strongly affect the appropriate use of drug therapy including medication adherence. No data on this parameter are available in the clinically important population of patients with type 2 diabetes (T2DM) undergoing coronary angiography. We therefore consecutively enrolled a cohort of 272 patients who underwent coronary angiography for the evaluation of suspected or established stable coronary artery disease (CAD) from March through December 2022. From our patients, 94 (34.4% of the total study population) had T2DM according to ADA criteria. Satisfaction with information regarding pharmaceutic therapy was measured using the validated Satisfaction with Information about Medicines Scale (SIMS-D) which consists of two sub-scales covering action and usage or potential problems, respectively. Further, health literacy, which includes the ability to understand and follow instructions for treatment was determined using the EU-HLS-Q16 questionnaire. SIMS-D questionnaires were returned by 196 (71.8%) and EU-HLS-Q16 by 229 (83.9%) patients. Median total SIMS-D scores did not differ significantly between T2DM patients and nondiabetic subjects (11, interquartile range (IQR) 9 vs. 9, IQR 8; p=0.383); independent of T2DM status patients scored significantly lower on items targeting satisfaction with information about potential problems of medication than the in sub-scales for action and usage (p&lt;0.001). In analysis of covariance, health literacy independently of age and T2DM predicted SIMS-D (F=18.55; p&lt;0.001). From our findings we conclude that satisfaction with information about medicines in angiographied coronary patients does not depend on the presence of T2DM but is significantly impacted by health literacy.

Disclosure
M. Ratz: None. J. Vogel: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
446-P: Antihyperglycemic Medication Initiation after Cardiovascular Hospitalization in Older Adults with Diabetes Increases Hypoglycemia without Improving Survival
Authors: FARAHVASH ARMIN , SIVASWAMY ATUL , ABDEL-QADIR HUSAM , LEGA ILIANA C. 
Published: June 2023

Background: The short-term safety and long-term cardiovascular benefits of initiating new antihyperglycemic medications at hospital discharge are unclear, especially for elderly patients with acute cardiovascular disease. This study aimed to determine if initiation of a new diabetes medication is associated with differences in outcomes in this patient population.
Methods: This was a population-based cohort study of individuals ≥65 years with diabetes on antihyperglycemic medication who were discharged from a hospitalization for heart failure, acute myocardial infarction, or stroke in Ontario, Canada from April 2011 to March 2019. We categorized individuals based on initiation of a new diabetes medication (initiators) within 30 days of discharge. Primary outcome was a composite of death or cardiovascular hospitalization. Secondary outcome was rate of hypoglycemia. We performed a Cox-regression on a propensity matched cohort.
Results: A total of 54,117 individuals were included, with 5,129 (9.5%) initiators and 48,988 (90.5%) non-initiators. Median age was 78 years (IQR 71-84) and 56.7% were male. Matched pair analysis included 4,844 pairs of initiators and non-initiators with standardized differences of ≤0.05 for all baseline variables. Median follow-up was near 2.2 years in both groups. There were no significant differences in the hazard of the composite of death/cardiovascular hospitalization (HR 0.97, 95% CI 0.92-1.02, p=0.18) or the hazard of death (HR 0.98, 95% CI 0.93-1.04, p=0.56). There was a higher risk of hypoglycemia among initiators (113 [2.3%] vs 76 [1.6%]) within one year of follow-up (HR: 1.49, 95% CI 1.12-1.98, p=0.007).
Conclusion: Starting a new antihyperglycemic medication in patients with diabetes who are discharged after hospitalization for a cardiovascular event is associated with an increased risk of hypoglycemia but does not reduce mortality or cardiovascular events.

Disclosure
A.Farahvash: None. A.Sivaswamy: None. H.Abdel-qadir: Other Relationship; AstraZeneca, JAZZ Pharmaceuticals. I.C.Lega: None.
45-OR: Newborn Adiposity and Cord Blood DNA Methylation—An Epigenome-Wide Association Study in HAPO with Validation in Gen3G
Authors: JOSEFSON JAMI L. , KUANG ALAN , SCHOLTENS DENISE , ALLARD CATHERINE , LOWE WILLIAM , HIVERT MARIE-FRANCE 
Published: June 2023

Differential cord blood DNA methylation (cb DNAm) in response to hyperglycemia in pregnancy may be associated with neonatal adiposity, a risk factor for childhood obesity. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study enrolled a multiethnic cohort to evaluate glycemia in pregnancy and newborn adiposity measured by skinfold thicknesses. We conducted an epigenome-wide association study using HAPO as a discovery sample and performed a replication study in an independent cohort, Gen3G. We analyzed cb DNAm with Illumina EPIC arrays (791,359 CpG sites after QC) on 2712 HAPO samples. We assessed the association between sum of 3 skinfolds and cb DNAm using linear regression models adjusted for maternal and offspring covariates and cell counts. We identified 90 CpG sites after accounting for multiple testing (Bonferroni-adjusted p&lt;0.05). Using these sites identified in HAPO, we conducted similar regression analyses in 139 Gen3G cb DNAm samples to replicate findings. Similar associations at 7 CpG sites were identified including loci near KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis, and IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds IGF1 and insulin, the latter especially during fetal life. These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity.

Disclosure
J.L.Josefson: None. A.Kuang: None. D.Scholtens: None. C.Allard: None. W.Lowe: None. M.Hivert: None.

Funding
National Institutes of Health (R01HD034243, R01DK118403)
453-P: Serum Lipocalcin-2 Levels, Fat Distribution, and the Risk of Cardiovascular Events—A Chinese Community-Based Longitudinal Cohort
Authors: HU TINGTING , XU YITING , SHEN YUN , WANG YUFEI , MA XIAOJING , BAO YUQIAN 
Published: June 2023

Aims: We aimed to explore whether there was a joint effect of serum lipocalcin-2 (LCN2) levels and fat distribution or interaction on the development of cardiovascular disease (CVD) in a middle-aged and elderly, community-based cohort.
Methods: This prospective study included 1,349 participants (583 men and 766 postmenopausal women) aged 50-80 years, without evident CVD from Shanghai communities in 2013-2014. All participants underwent complete risk factor survey and body composition measurement at baseline. The follow-up assessment was conducted in 2021-2022 for cardiovascular events via phone calls and electronic medical records. Magnetic resonance imaging was used to assess fat distribution including subcutaneous fat area (SFA) and visceral fat area (VFA). SFA ≥ 75th percentile was classified as high, and VFA ≥ 80 cm2 was defined as high.
Results: During a mean follow-up of 7.6 years, 140 (10.4%) cases of cardiovascular events occurred, with 56 cases of ischemic heart diseases and 84 cases of cerebrovascular events. In fully adjusted Cox proportional hazards models, increasing baseline serum LCN2 levels were associated with a higher risk of cardiovascular events in women (HR for per 10 ng/mL increase: 1.11, 95%CI 1.02-1.20), but disappeared in men (HR for per 10 ng/mL increase: 1.00, 95%CI 0.93-1.08). Fat distribution modified the association between serum LCN2 levels and cardiovascular events in women, strengthening the association at low VFA levels (P interaction = 0.024), regardless of SFA levels (P interaction = 0.190).
Conclusions: Increasing LCN2 levels were independently and positively associated with the risk of cardiovascular events in women, which could be interacted by fat distribution at baseline.

Disclosure
T.Hu: None. Y.Xu: None. Y.Shen: None. Y.Wang: None. X.Ma: None. Y.Bao: None.
458-P: Proinflammatory Macrophage Phenotype Modulates Vascular Smooth Muscle Cell Differentiation via the Histone Demethylase JMJD3
Authors: MANGUM KEVIN D. , JOSHI AMRITA , MAZUMDER PURBA , WOLF-FORTUNE SONYA , BARRETT EMILY , MOORE BETHANY , DAVIS FRANK M. , GALLAGHER KATHERINE 
Published: June 2023

Patients with diabetes are at increased risk of a multitude of vascular diseases, including atherosclerosis, which is driven by macrophage-mediated inflammation. While it is known that atherosclerosis is characterized by a proliferative, synthetic smooth muscle phenotype that underlies disease, the exact role of other cell types, namely myeloid cells and their interaction with smooth muscle cells is less understood. Furthermore, how diabetes modifies atherosclerotic severity is another important question. To address this, we performed an epigenetic superarray to identify key chromatin modifying enzymes in vascular smooth muscle cells (vSMC) from normal diet (ND) and diabetic-induced obese (DIO) aortas. We identified the histone demethylase, JMJD3, which was significantly decreased in DIO compared to ND vSMC (p&lt;0.05). Furthermore, in our single cell RNA-seq data set from human atherosclerotic lesions, JMJD3 was expressed in smooth muscle cells. It is known that macrophages in atherosclerotic lesions exhibit a pro-inflammatory phenotype. To model this pro-inflammatory process, we stimulated bone marrow derived macrophages with LPS and found that supernatant from LPS-stimulated BMDMs significantly inhibited smooth muscle specific gene expression (SMA, SM22, CNN1, SM-MHC) as well as expression of JMJD3 compared to control media (p&lt;0.05). Additionally, siRNA-mediated knockdown of JMJD3 in vSMC reduced SMC-specific gene expression, and treatment of mouse aortic vSMC with the JMJD3 selective inhibitor, GSK4J, decreased smooth muscle gene expression (p&lt;0.05). Our data shows that pro-inflammatory macrophages drive reduced vascular smooth muscle gene expression and that JMJD3 in SMC is a regulator of this process. These results implicate JMJD3 in macrophage-smooth muscle cell crosstalk in the pro-inflammatory state and identify it as a potential therapeutic target in the management of atherosclerosis.

Disclosure
K.D.Mangum: None. A.Joshi: None. P.Mazumder: None. S.Wolf-fortune: None. E.Barrett: None. B.Moore: None. F.M.Davis: None. K.Gallagher: None.

Funding
National Institutes of Health (1F32DK131799-01); American College of Surgeons; Vascular & Endovascular Surgery Society
46-OR: Amelioration of Insulin Resistance after Delivery Lowers the Risk of Postpartum Type 2 Diabetes in Women with Gestational Diabetes Mellitus
Authors: SON HEEJUN , HO MOON JOON , CHO NAM H. , CHUL JANG HAK 
Published: June 2023

Background: Detecting the risk of postpartum diabetes in women with gestational diabetes mellitus (GDM) is essential for proper intervention. We investigated whether changes in insulin sensitivity after delivery affect the risk of diabetes in Korean women with GDM.
Method: In a prospective cohort including women with GDM, we included those who attended the postpartum visit at 2 months and yearly thereafter. The change in insulin sensitivity was defined as ∆Matsuda index, the difference between the initial postpartum visit and during pregnancy. We analyzed the risk of diabetes according to tertiles of ∆Matsuda index.
Results: During 3.4 years of follow-up, 60 out of 347 subjects (17.3%) developed diabetes. The incidence of diabetes decreased as the tertile of ∆Matsuda index increased (26.7%, 17.2%, and 7.8%, P = 0.001). Subjects in the second and third tertile of ∆Matsuda index showed lower risk of diabetes compared to the subjects in the first tertile (HR, 0.45; 95% CI, 0.24-0.82; HR, 0.18; 95% CI, 0.07-0.48) after adjusting for age, family history of diabetes, gravida, lactation, fasting glucose, and postpartum BMI.
Conclusion: Amelioration of insulin resistance lowers the risk of diabetes in Korean women with GDM. Although the assessment of insulin sensitivity is not standardized, changes in insulin sensitivity may be a useful predictor for diabetes in women with GDM.

Disclosure
H.Son: None. J.Moon: None. N.H.Cho: None. H.Jang: None.
460-P: Pulse Pressure Predicts Future Cardiovascular Events in Cardiovascular Disease Patients with Type 2 Diabetes
Authors: PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2023

Pulse pressure, i.e. the difference between systolic and diastolic blood pressure is a measure of arterial stiffness, which is a strong predictor of cardiovascular risk. Its impact on the risk of cardiovascular events in patients with type 2 diabetes (T2DM) is unclear and is addressed in the present study. We enrolled a large high risk cohort of 1327 patients with established cardiovascular disease (1009 patients with angiographically proven stable CAD and 318 patients with sonographically proven peripheral artery disease). T2DM was diagnosed according to ADA criteria. Prospectively, cardiovascular events were recorded over a mean follow-up period of 9.3±4.6 years. At baseline, pulse pressure was 60±17 mmHg in patients with T2DM (n=481) and 57±17 mmHg in subjects who did not have T2DM (p=0.002). During follow-up, 614 patients suffered cardiovascular events. The event rate was higher in patients with T2DM than in those who did not have diabetes (54.8% vs. 42.2% p&lt;0.001). Pulse pressure significantly predicted cardiovascular events after multivariate adjustment including diabetes status in the total study cohort, with a standardized adjusted hazard ratio (HR) of 1.14 [1.05-1.24]; p=0.003. Importantly, pulse pressure also predicted cardiovascular events in the very high risk subgroup of cardiovascular disease patients with T2DM (HR 1.20 [1.06-1.37]; p=0.006). We conclude that pulse pressure predicts cardiovascular events in cardiovascular disease patients with T2DM.

Disclosure
T.Plattner: None. C.H.Saely: None. A.Vonbank: None. A.Mader: None. L.Sprenger: None. M.Maechler: None. B.Larcher: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None.