bluuebunny/crossref_metadata_2025_split huggingface dataset:
420-P: Effects of Nonalbuminuric Type 2 Diabetes Mellitus on Renal Outcomes
Authors: CHOI DUGHYUN , PARK SAMEL , YOUNG LEE EUN 
Published: June 2024

Introduction & Objective: The classic pattern of diabetic kidney disease is typically followed by microalbuminuria. However, the pure impact of type 2 diabetes mellitus (T2D) without albuminuria on renal outcomes is not fully understood. This study aimed to investigate the renal outcomes in non-albuminuric T2D compared to non-albuminuric non-T2D subjects.
Methods: Data from the National Health Insurance Service-National Sample Cohort of Korea from 2009 to 2015 were analyzed. Subjects with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 at baseline and within the normal range of albuminuria were included. They were divided into T2D and non-T2D groups. The primary outcome was a composite renal outcome, consisting of the initiation of renal replacement therapy and a decline of ≥ 40% in eGFR from baseline.
Results: A total of 77,267 patients were analyzed (11,957 in the T2D group vs. 65,310 in the non-T2D group). In a linear mixed model, the T2D group showed a significantly greater annual decline in eGFR of -0.113 ml/min/1.73 m2 (95% CI: -0.222 to -0.003, p = 0.044) compared to the non-T2D group. The primary outcome, the adjusted hazard ratio for the composite renal outcome, was 1.57 (95% CI: 1.28-1.92, p &lt; 0.001).
Conclusion: Non-albuminuric T2D was associated with a greater annual decline in renal function and had a 1.5-fold increased risk of adverse renal outcomes compared to non-albuminuric non-T2D subjects.

Disclosure
D. Choi: None. S. Park: None. E. Lee: None.

Funding
National Research Foundation of Korea grant funded by the Korean government (2021R1G1A1009254)
421-P: Ferritin and COVID-19 Infection and Outcomes in American Indian and Alaska Native Dialysis Patients with Diabetes
Authors: HU MING , QUANDELACY TALIA , WANG YUEDONG , KOTANKO PETER , CONWAY REBECCA B. 
Published: June 2024

American Indians/Alaska Natives (AIAN) bear the greatest burden of diabetes and are overrepresented in the dialysis population. They were also hardest hit by COVID-19, w/higher mortality rates than any U.S. racial/ethnic group. Early in the pandemic, hyperferritinemia was prognostic of poor COVID-19 outcomes, including death. We determined the association of ferritin w/ COVID-19 infection, hospitalization, and mortality in AIAN dialysis patients w/ diabetes. We followed 1,065 AIAN in-center hemodialysis patients w/ diabetes from January 2020 to March 2022. For incident COVID infection, baseline ferritin was defined as the average from one year prior to two weeks prior to RT-PCR confirmed COVID-infection (days-365,-14). Change in ferritin was defined as the difference between the baseline average and two week prior average (-14,0) to the PCR positive test date. For non-infected patients, a randomly selected date following the distribution of PCR positive dates of COVID patients was chosen as the test date. Logistic regression assessed the association of ferritin and its change w/ COVID-19 infection, hospitalization and mortality, adjusting for age, sex, race, vaccination status, vintage, and lab values. During follow-up, the cumulative incidence of infection was 35.7%; in the infected, 26.7% were hospitalized and 12.6% died. While baseline ferritin was not linked to infection risk (p=0.42), TSAT (p=0.02) and ferritin change (p=0.09) were marginally. In the infected, ferritin two weeks prior to RT-PCR confirmed diagnosis were linked to hospitalization (p=0.02), while ferritin change was not (p=0.59). Neither baseline nor ferritin change was linked w/ mortality; but lower baseline hgb (p=0.09), higher neutrophils (p=0.09) and neutrophil to lymphocyte ratio (p=0.06) showed weak relationships w/ mortality. Ferritin was associated w/ future risk of COVID-19 infection and hospitalization but not mortality in AIAN dialysis patients w/ diabetes.

Disclosure
M. Hu: None. T. Quandelacy: None. Y. Wang: None. P. Kotanko: Other Relationship; Fresenius Medical Care. R.B. Conway: None.
43-PUB: A Bibliometric Analysis of Machine Learning and Type 2 Diabetes from 2010 to 2023
Authors: YANG YANLING , LIU ZHIGU , LIN BEISI , CHEN DANRUI , YAN JINHUA , ZENG LONGYI , XU WEN 
Published: June 2024

Objective: Machine learning in the research on type 2 diabetes (T2D) has garnered attention in recent years. Nonetheless, few studies offer a thorough picture of the knowledge generation landscape in this field. This comprehensive bibliometric analysis was conducted to discover global research trends and networks and to emphasize the most prominent countries, institutions, and key topics in this domain.
Methods: Articles on the link between machine learning and T2D from 2010 to 2023 were searched in the Science Citation Index-Expanded of Web of Science Core Collection. The results were classified into categories of prediction, screening and management. CiteSpace software, Vosviewer, the R package "bibliometrix" and the Online Analysis Platform of Literature Metrology were used to analyze the data.
Results: A total of 611 articles were retrieved on the link between machine learning and T2D. The number of publications increased dramatically in the past 5 years, with a sharply increase in the last 3 years. The United States dominated the field until 2021, and the dominance of China started in 2022. The United States was the most frequently involved country in international cooperation. Harvard Medical School was the most productive university. The co-citation keyword clustering labels displayed eight main clusters: precision medicine, counterfactual prediction, risk scoring, diabetic retinopathy, predictive model, gut microbiome, clinical decision support system, and bariatric surgery. The keyword bursts analysis indicated that validation, risk prediction, predictive model, predictor, and metabolomics were the research hotspots with high strength.
Conclusion: Machine learning is now being increasingly applied in the field of prediction, screening and management of T2D, especially over the last years with exponential growth. This bibliometric study provided systematic information and guidance to help explore the application and practice of machine learning in T2D for future research.

Disclosure
Y. Yang: None. Z. Liu: None. B. Lin: None. D. Chen: None. J. Yan: None. L. Zeng: None. W. Xu: None.

Funding
Natural Science Foundation of Guangdong Province (2022A1515012364)
450-P: Pulse Pressure as a Predictor of Cardiovascular Events in Cardiovascular Disease Patients with Differing Glycemic State
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

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. The power of pulse pressure to predict cardiovascular events in patients with differing glycemic state is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in a high-risk cohort of 1787 patients with cardiovascular disease (1472 patients with angiographically proven coronary artery disease and 315 with sonographically proven peripheral artery disease), over a mean follow-up period of 10.7±5.0 years. At baseline, pulse pressure significantly increased from patients with NFG (n=690) over those with IFG (n=505) to those with T2DM (n=592; 56±17 mmHg, 58±15 mmHg and 59±18 mmHg, respectively; ptrend=0.002). During follow-up, 913 of our patients suffered cardiovascular events; the incidence of cardiovascular events increased significantly from subjects with NFG over those with IFG to those with T2DM (49.9%, 44.2% and 60.3%, respectively; ptrend&lt;0.001).Pulse pressure in the total study population predicted cardiovascular events (standardized adjusted HR 1.13 [1.05-1.22], p&lt;0.001) in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index and LDL cholesterol and also after additional adjustment for the baseline glycemic state (HR=1.12 [1.04-1.21], p=0.002). In subgroup analyses, standardized adjusted HRs were 1.15 [1.02-1.30], p=0.027), 1.00 [0.85-1.17], p=0.971) and 1.17 [1.05-1.31], p=0.006) in patients with NFG, IFG and T2DM, respectively. An interaction term puls pressure by glycemic state was not significant (p=0.310), indicating that the glycemic state did not significantly impact the power of pulse pressure to predict cardiovascular events. From our data we conclude that pulse pressure is a predictor of cardiovascular events in CVD patients irrespective of the baseline glycemic state.

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.
456-P: The ApoB/LDL-C Ratio Predicts Cardiovascular Events in Coronary Artery Disease Patients Independent of Type 2 Diabetes Status
Authors: LARCHER BARBARA , PLATTNER THOMAS , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

A high ApoB/LDL-C ratio reflects small LDL particle size which like type 2 diabetes (T2DM) is associated with insulin resistance. Whether the ApoB/LDL-C ratio and the presence of T2DM are mutually independent predictors of cardiovascular events is unclear and is addressed in the present study. We enrolled a large high-risk cohort of 1200 patients with coronary artery disease. T2DM was diagnosed according to current ADA guidelines. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.5±4.9 years. At baseline, the ApoB/LDL-C ratio was significantly higher in patients with T2DM (n=422) than in subjects who did not have T2DM (0.81±0.18 vs. 0.74±0.15 p&lt;0.001). During follow-up, 662 patients suffered cardiovascular events. The Apo B/LDL-C ratio predicted cardiovascular events in univariate analysis (HR=1.11 [1.03-1.20] p= 0.006), and the event rate was higher in patients with than in those without T2DM (62.2% vs. 52.3%; p=0.001). In a multivariate adjusted Cox regression model both the ApoB/LDL-C ratio and T2DM significantly predicted cardiovascular events in a mutually independent manner, with standardized adjusted HRs of 1.11 [1.03-1.20]; p=0.008 and 1.39 [1.18-1.64]; p&lt;0.001, respectively. We conclude that in subjects with coronary artery disease the ApoB/LDL-C and T2DM are mutually independent predictors of cardiovascular events.

Disclosure
B. Larcher: None. T. Plattner: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
464-P: The Visceral Adiposity Index Predicts Cardiovascular Events Both in Coronary Artery Disease Patients With and in Those Without Diabetes
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyceride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study. We prospectively investigated 927 patients with angiographically diagnosed CAD over a mean follow-up time of 8.2±4.3 years. At baseline, the VAI was significantly higher in patients with T2DM (n=303) than in those who did not have diabetes (6.5±5.2 vs. 4.8±4.9; p&lt;0.001). During follow-up, we recorded 385 cardiovascular events. The VAI significantly predicted the incidence of cardiovascular events both univariately (standardized HR 1.09 [1.02-1.16]; p=0.011) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.11 [1.04-1.18]; p=0.002); also T2DM significantly predicted cardiovascular events in this fully adjusted model (adjusted HR 1.26 [1.04-1.52]; p=0.018) independently from the VAI. We conclude that the VAI and T2DM are mutually independent predictors of cardiovascular events in patients with CAD.

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.
47-PUB: FRAME—An Education Program for Newly Diagnosed Youth with Type 2 Diabetes
Authors: VAKHARIA MILI , ELISA DIAZ MARIA , MCKAY SIRIPOOM , LYONS SARAH , SONABEND RONA Y. , KIM GRACE K. 
Published: June 2024

Background: We launched a new multidisciplinary pediatric type 2 diabetes (T2D) inpatient education program, FRAME (Follow a Balanced Meal, Reduce Insulin Resistance with Lifestyle Change, Adhere to Medication, Monitor Blood Glucose & Comorbidities, and Engage Support System). It focused on MyPlate method and fixed insulin dosing rather than based on grams of carbohydrates. Our quality improvement (QI) aim was to decrease the percentage of youth with new onset T2D, diagnosed less than 6 months, placed on carbohydrate-based insulin dosing from baseline of 19% to 14% by December 2023.
Methods: Our team implemented the following Plan-Do-Study-Act cycles: 1. Created a FRAME Works T2D education program 2. Educated providers and ancillary staff 3. Implemented the education at all three hospitals 4. Initiated a post-hospitalization discharge knowledge assessment test.
Results: P-chart showed shift in center line with percentage of patients with T2D, diagnosed less than 6 months, on a carbohydrate-based dosing regimen decreasing from baseline of 19% to 10%, from December 2022 to December 2023 (Figure 1).
Conclusions: Our QI project successfully facilitated interprofessional led patient education for youth with T2D using the FRAME program. Our next steps are to develop an outpatient education curriculum with treatment algorithm and outcomes.

Disclosure
M. Vakharia: None. M. Diaz: None. S. Mckay: None. S. Lyons: None. R.Y. Sonabend: None. G.K. Kim: None.
471-P: Anti-NFKB Inhibitor Beta Antibody Correlates with Cardiovascular Disease in Type 1 Diabetic Patients with Autoimmune Disease
Authors: PARK KYOUNGMIN , PHAM LINDA , LI QIAN , GREGORY YU MARC , FU JIALIN , VISHVA TEJA JANGOLLA SURYA , WU I-HSIEN , KING GEORGE L. 
Published: June 2024

Cardiovascular disease (CVD) is a major cause of mortality in Type 1 diabetes (T1D). Studies suggest that autoimmunity may influence CVD development in T1D. We created a novel T1D-CVD mouse model by deleting ApoE via CRISPR/Cas9 editing in nonobese diabetic (ApoE-/-/NOD) mice, an autoimmune T1D model, and observed that both diabetic and nondiabetic ApoE-/-/NOD mice showed autoimmune insulitis and greater atherosclerotic lipid deposition and plaque formation compared to CongApoE-/‘- wild type (WT) mice. Plasma studies with autoantigen proteomic microarray from people with long-duration T1D&gt;50 years (“Medalists”), identified potential autoantibodies (AAb) targeting antigens in aortic plaques, which correlated to coronary artery calcium (CAC). One protein, nuclear factor-KB inhibitor beta (NFKBIB, p=0.0017), was higher in plasma of Medalists positive for HLA T1D risk alleles (HLA+) compared to HLA(-) Medalists. To quantify circulating anti-NFKBIB in Medalist samples, we developed an immunoassay using novel electrochemiluminescence technology. Our findings showed higher anti-NFKBIB AAb in HLA(+) versus HLA(-) Medalists. Moreover, in the HLA(+) group, higher anti-NFKBIB AAb was seen in those with CVD. To corroborate these findings from Medalist patients, we analyzed plasma from ApoE-/-/NOD mice with autoimmune T1D, as well as control nondiabetic CongApoE/NOD mice. Immunoblot analysis showed that only isolated IgG from plasma of ApoE-/-/NOD mice detected NFKBIB in aortic lysates and/or purified recombinant NFKBIB protein in a concentration-dependent manner, relative to IgG from control mice. Flow cytometry analysis of immunocytes revealed twofold increases in blood and para-aortic B- (CD19+, p=0.012) and T-cell (CD4+, p=0.008) populations of ApoE-/-/NOD mice compared to WT mice. These suggest that anti-NFKBIB AAb is a novel AAb present in people and mouse models with T1D and atherosclerosis, and may contribute to CVD development in T1D.

Disclosure
K. Park: None. L. Pham: None. Q. Li: None. M. Yu: None. J. Fu: None. S. Jangolla: None. I. Wu: None. G.L. King: None.

Funding
5R01HL161864-02, Beatson foundation #5R01HL161864-02
472-P: Molecular Pathogenesis of Sex-Specific Vascular Contributions to Cognitive Impairment and Dementia and in Type 1 Diabetes
Authors: WILSON SANTOS ED , KHATOON SUBIKA , ZHENG YUN-MIN , WANG YONG-XIAO 
Published: June 2024

Introduction & Objective: Type 1 diabetes (T1D) is a serious disease that affects millions of people worldwide and is a major factor for vascular contributions to cognitive impairment and dementia (VCID). However, whether and how sex affects VCID in diabetics is rarely reported. In this study, we compared cognitive and memory impairments in male and female mice with T1D and evaluated the underlying molecular mechanisms.
Methods: We injected streptozotocin (STZ) and then measured cerebral blood flow, ROS production, Tau, and Chk2 expression by Western blotting.
Results: Our findings indicate that intraperitoneal STZ-injection induced T1D in both genders of mice, showing largely elevated blood glucose, and decreased body weight. However, male diabetic mice showed greater cognitive impairment determined by an open-field test and memory loss measured by a novel object recognition test. Interestingly, ROS generation in isolated mitochondria and mitochondrial complex III from cerebral arterial smooth muscle (CASM) tissues was greater in male diabetic mice. ROS production in isolated mitochondria and mitochondrial complex III from cerebral cortex tissues was increased similarly in both male and female diabetic mice. We further found that male diabetic mice had higher DNA damage, as demonstrated by greater check kinase 2 (Chk2) phosphorylation in CASM tissues. Tau phosphorylation in CASM tissues was also largely increased in diabetic mice; this diabetic increase was no different between males and females. Noticeably, mitochondrial and complex III ROS production, Chk2, and tau phosphorylation all had similar increases in cerebral cortex tissues from both male and female diabetic mice.
Conclusion: Taken together, we conclude that T1D may cause greater mitochondrial complex III ROS production, greater DNA damage and greater Chk2 phosphorylation in male CASM tissues, thereby leading to more serious cognitive impairment and memory loss in male than female T1D.

Disclosure
E. Santos: None. S. Khatoon: None. Y. Zheng: None. Y. Wang: None.

Funding
R01HL122865R03AG070784R01HL108232
477-P: Peripheral Neuropathy—Evaluation of DPNCheck vs. mTCNS in Type 1 Diabetes
Authors: MARION LIPI A. , NEVAREZ CRYSTABELLA E. , MURTHY ANANYA B. , YU ELAINE W. 
Published: June 2024

Introduction: The handheld DPNCheck (DPNC) nerve conduction study (NCS) device has shown high sensitivity (SENS) and specificity (SPEC) against classical NCS for detecting peripheral neuropathy (PN), but studies comparing DPNC to clinical assessments are lacking. We aimed to evaluate DPNC against a validated clinical reference standard in adults with T1D.
Methods: Among 88 adults &gt;50 yrs with T1D, we assessed PN with the modified Toronto Clinical Neuropathy Scale (mTCNS) and bilateral sural nerve conduction velocity (VEL) and action potential amplitude (AMP) with DPNC. Abnormal AMP or VEL &lt;u&gt;&gt;&lt;/u&gt;1 leg=DPNC+. We used McNemar’s test and calculated SENS and SPEC to compare DPNC to mTCNS (score &lt;u&gt;&gt;&lt;/u&gt;3=PN+) as the reference.
Results: Mean age was 63+6 yrs, T1D duration 46±10 yrs and A1c 7.1±1%; 52% were male. Mean mTCNS score was 5.2+5, AMP 42+10 m/s and VEL 4.8+3 µV. Correlation between mTCNS and worse leg AMP and VEL was -0.36 and -0.52, respectively (p&lt;0.001). The proportion of subjects PN+ by mTCNS was similar to those DPNC+ using standard manufacturer cutoffs (DPNC-std; p=0.85) but significantly higher in those DPNC+ using age and height adjusted cutoffs (DPNC-adj; p&lt;0.001). DPNC-adj had 94% SENS but 28% SPEC; DPNC-std had 71% SENS and 63% SPEC.
Conclusion: DPNC has high SENS for detecting PN in T1D. Lower SPEC may reflect detection of subclinical PN rather than misclassification of true negatives. DPNC alone or combined with mTCNS may aid in early PN detection.

Disclosure
L.A. Marion: None. C.E. Nevarez: None. A.B. Murthy: None. E.W. Yu: Research Support; Amgen Inc.

Funding
National Institutes of Health (T32DK007028)
480-P: Serum Uric Acid–to–Creatinine Ratio Is an Independent Risk Factor of Sudomotor Dysfunction in Patients with Type 2 Diabetes
Authors: PENG JIE , CHEN XUEYAN , XU HUAN , TANG XIAOYUN , SHUI XING , YAN JINHUA , XU WEN , YAO BIN , DENG HONGRONG , YANG XUBIN 
Published: June 2024

Object: This study aimed to explore the relationship between serum uric acid to creatinine ratio (UCR) and sudomotor function in patients with T2DM.
Methods: Serum uric acid and serum creatinine were measured with an automated biochemistry analyzer. UCR was calculated. Sudomotor function was assessed through electrochemical skin conductance (ESC) measurements conducted with the SUDOSCAN device.
Results: A total of 781 patients with T2DM were enrolled (59% male, 55.09±13.23 years). Patients were further divided into three groups based on the mean ESC of the hand and foot (MEHF): the group with sudomotor severe dysfunction (SDF group, MEHF&lt; 40μS), the sudomotor moderate dysfunction group (MDF group, 40μS≤ MEHF≤ 60μS), and the group with normal sudomotor function (NSF group, MEHF &gt; 60μS). Compared with the NSF group, level of UCR of patients in MDF group and SDF group was significantly lower (P &lt; 0.0001) (Table 1). Spearman correlation analysis showed that the MEHF was negatively correlated with UCR (r = -0.144, P&lt;0.0001). After dividing UCR into tertiles, multivariate logistic regression analysis demonstrated that participants in the lowest UCR group had a significantly higher risk of sudomotor dysfunction by 67.2% than those in the highest group (OR = 1.672, 95%CI 1.171-2.387, P =0.005).
Conclusion: UCR is an independent risk factor of sudomotor dysfunction in patients with T2DM.

Disclosure
J. Peng: None. X. Chen: None. H. Xu: None. X. Tang: None. X. Shui: None. J. Yan: None. W. Xu: None. B. Yao: None. H. Deng: None. X. Yang: None.