bluuebunny/crossref_metadata_2025_split huggingface dataset:
382-P: Clinical Characteristics of Insulinoma Patients with Secondary Adrenal Insufficiency
Authors: WANG XIA , YU LUO , CHEN YAO , HUI XIE J. 
Published: June 2024

Objective: The purpose of this study is to investigate the clinical characteristics and high-risk factors of insulinoma combined with secondary adrenal cortical insufficiency.
Methods: This was a retrospective study including 44 surgically confirmed insulinoma patients and 16 diabetes patients with hypoglycemia. IBM SPSS Statistic 27 was used for statistical analysis.
Results: The proportion of low morning cortisol levels was significantly higher in insulinoma patients than in diabetes patients with hypoglycemia. Compared to diabetes patients with hypoglycemia, insulinoma patients had lower blood glucose levels during hypoglycemia. Additionally, serum cortisol levels in the morning and midnight were lower in insulinoma patients, with a significantly greater decrease in morning serum cortisol levels (Fig.1). In insulinoma patients group, both the insulin release index(IRI) &gt;1.2 group and the insulin levels &gt;38.6uIu/ml group had larger tumor diameters than the IRI &lt;0.3 group and the insulin levels 18.8-38.6uIu/ml group, respectively. The tumor diameters ≥1cm group had lower morning serum cortisol and ACTH than the tumor diameters&lt;1cm group.
Conclusion: Our study suggests that larger tumors may be associated with secondary adrenal insufficiency in insulinoma patients, thereby increasing perioperative risks of insulinoma patients.

Disclosure
X. Wang: None. L. Yu: None. Y. Chen: None. X.J. Hui: None.
394-P: Empagliflozin Ameliorate Renal Fibrosis in DKD
Authors: CAI XIANG , CAO HUANYI , WANG MEIJUN , YU PIAOJIAN , LIANG XIAOQI , LIANG HUA , XU FEN , CAI MENGYIN 
Published: June 2024

Introduction & Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal outcomes in diabetic kidney disease (DKD), but the mechanisms underlying this effect are not fully elucidated. Renal fibrosis is an important cause leading to renal failure in DKD. The purpose of this study is to investigate whether SGLT2 inhibitor empagliflozin can improve renal fibrosis in DKD models.
Methods: The DKD models used in this study include CD-1 mice treated with streptozotocin (STZ), C57/BL6J mice fed with high-fat diet (HFD), and ob mice fed with methionine/choline-deficient diet (MCD) /ob mice. Mice were administered empagliflozin (10mg/kg) daily by gavage for 4 to 8 weeks. Renal fibrosis was examined by pathological staining, immunofluorescence staining and western blot.
Results: After DKD induction, renal fibrosis was observed in three DKD mouse models indicated by PAS staining and Masson staining. Collagen III α1 chain (COL3A1) and alpha-smooth muscle actin (αSMA) were upregulated in DKD mouse models detected by immunofluorescence staining and western blot. Empagliflozin significantly ameliorated pathological changes of renal fibrosis and downregulated COL3A1 and αSMA.
Conclusion: Empagliflozin ameliorate renal fibrosis in DKD.

Disclosure
X. Cai: None. H. Cao: None. M. Wang: None. P. Yu: None. X. Liang: None. H. Liang: None. F. Xu: None. M. Cai: None.
397-P: The C/EBPß-XOR Axis and Genetic Risk for Diabetic Kidney Disease
Authors: EKPERIKPE UBONG , YU LIPING , DAEHN ILSE S. 
Published: June 2024

Introduction & Objective: Diabetic kidney disease (DKD) is the leading single cause of end-stage renal disease in the United States. Approximately 30% of diabetics develop DKD with comparable blood glucose levels, indicating a significant genetic predisposition. However, the underlying mechanisms that contribute to differential susceptibility are unclear. The glomerulus is the primary site of injury with hypertrophy and podocyte depletion being the hallmarks for progressive DKD. We have demonstrated that mitochondrial oxidative damage in glomerular endothelial cells (GECs), leads to podocyte loss via GEC-to-podocyte crosstalk in DKD susceptible DBA/2J (D2) mice compared to DKD resistant C57BL/6J (B6) mice.
Methods: We mapped potential genetic loci associated with podocyte depletion after long-term diabetes (6mth using 39 strains of BXD, parental B6 and D2 mice). We identified a significant cis-acting variant in the promoter of xanthine oxidoreductase (Xor). XOR catalyze the oxidation of purine substrates to uric acid and reactive oxygen species (ROS). Using CRISPR/Cas9 to knock-in the Xor risk variant into DKD-resistant B6 mice, we generated mutant B6-Xorem1 mice with significantly higher XOR activity than B6.
Results: This risk variant is a transcription factor binding site to C/EBPβ. We observed higher C/EBPβ expression in GECs from diabetic B6-Xorem1 mice. B6-Xorem1 mice had increased mitochondrial oxidative stress in GECs, podocyte depletion, basement membrane thickening, albuminuria, glomerulosclerosis and tubular injury. These changes were prevented with XOR inhibition. Interestingly B6-Xorem1 mice developed age-associated glomerulosclerosis. In vitro studies support a Xor and mitochondrial ROS interplay in endothelial cells that resulted in GEC dysfunction.
Conclusion: Xor promoter variants are causal for DKD susceptibility and may predispose to aging and other diabetic complications.

Disclosure
U. Ekperikpe: None. L. yu: None. I.S. Daehn: None.

Funding
National Institutes of Health (R01DK097253)
408-P: Long-Term Improvement in Renal Function following Intensive Lifestyle Intervention in Patients with Diabetes and Obesity—A 15-Year Longitudinal Study
Authors: SALAH TAREQ , AL-BADRI MARWA , ALMASIH BARBAR ASKAR ABD , KHATER ABDELRAHMAN , DHAVER SHILTON E. , MOTTALIB ADHAM , HAMDY OSAMA 
Published: June 2024

Nearly 30% of patients with diabetes mellitus (DM) develop diabetic nephropathy over time. The long-term effect of weight loss, through lifestyle intervention, on kidney function remains unknown.We evaluated 94 patients with obesity and DM (12.8% type 1 DM and 87.2% type 2 DM, age 53.9±9.9 years, diabetes duration 10.9±10.3 years, weight 108.0±18.8 kg, and BMI 38.1±5.0 kg/m2) who enrolled in a 12-week multidisciplinary intensive lifestyle intervention (ILI) conducted in real-world clinical practice. Patients were prospectively followed for over 15 years. At one year, we stratified participants according to their percentage weight loss into: group A, who maintained ≥7% weight loss (48.9%) and group B, who maintained &lt;7% weight loss (51.1%). At 15 years, the full cohort maintained an average of 8.0±2.8 kg weight loss (10.1±19.6%, p&lt;0.0001). Group A lost 12.8±4.1 kg (15.1±21.9%, p&lt;0.0001) and group B lost 3.9±3.4 kg (5.5±17.6%, p=0.024). A1C did not change from baseline in group A, but increased in group B (0.6±0.5%, p=0.027). Systolic blood pressure did not change in both groups. Diastolic blood pressure decreased only in group A from 77±3 mmHg to 73±3 mmHg (p=0.03). LDL-cholesterol and HDL-cholesterol significantly improved in both groups, however, triglycerides significantly increased in both groups. Estimated glomerular filtration rate (eGFR) increased in group A from 79.5±12.5 to 92.5±15.3 mL/min/1.73 m2 (p=0.02) and in group B from 80.5±7.5 to 90.8±13.3 mL/min/1.73 m2 (p=0.02). There was no significant change in urinary albumin/creatinine ratio from baseline or serum creatinine in both groups.We conclude that 12 weeks of ILI have a sustained improvement of renal function for up to 15 years after intervention. This improvement is more pronounced in those who maintained ≥7% weight loss at one year.

Disclosure
T. Salah: None. M. Al-Badri: None. A. Barbar Askar: None. A. Khater: None. S.E. Dhaver: None. A. Mottalib: None. O. Hamdy: Research Support; Eli Lilly and Company, Novo Nordisk. Consultant; Abbott Nutrition. Stock/Shareholder; Healthimation. Research Support; Gilead Sciences, Inc. Advisory Panel; Nemaura Medical, Twin Health, L-Nutra Inc.
410-P: Evaluating the Performance of the 2021 CKD–EPI Equation in People with Diabetes
Authors: KWOK RODNEY , MACISAAC RICHARD , KISHORE KARTIK , ZAFARI TINA , HACHEM MARIAM , KOYE DIGSU , RESEARCH GROUP DCCT/EDIC , SCHAEFFNER ELKE , JEONG TAEDONG , MIN WON-KI , BJORNSTAD PETTER , CHURILOV LEONID , EKINCI ELIF I. 
Published: June 2024

Introduction: In 2021, CKD-EPI equation without the race coefficient (2021 CKD-EPI equation) was recommended for use in clinical practice by international guidelines. The performance of the 2021 equation in people with diabetes is unknown. This study aims to assess and compare the performance of the 2021 CKD-EPI equation to the 2009 CKD-EPI equation in individuals with type 1 and/or type 2 diabetes.
Methods: Datapoints (n=16,182) were collected from people with type 1 and type 2 diabetes from six international cohorts (Diabetes Control and Complication Trial [DCCT, USA], Colorado [USA], Germany, Korea, Spain, and Australia), with mGFR assessed using exogenous filtration markers. The intra-class correlation coefficient between mGFR and eGFR for 2009 CKD-EPI equation and 2021 CKD-EPI equation was estimated using (a) a one-step intra-individual participant data meta-analysis approach, and (b) a four-level mixed-effect linear model which included studies and individual participants as first and second level random effects, method of measurement as third level fixed effect and time as fourth level random effect.
Results: Overall performance of the 2009 CKD-EPI equation was excellent (ICC: 0.96, 95%CI: 0.88, 0.99) and 2021 CKD-EPI equations (ICC: 0.87, 95%CI: 0.77, 0.93) was good. However, subgroup analyses based on clinically relevant GFR ranges (&lt;30, 30-59, 60-89 ml/min/1.73m2) revealed poor agreement between mGFR and eGFR measurements for the 2009 CKD-EPI equation (ICC: 0.41, 0.43, 0.40 respectively) and excellent agreement for GFR ≥90 ml/min/1.73m2 (ICC: 0.92). The 2021 CKD-EPI equation revealed poor agreement across GFR ranges &lt;30, 30-59 and 60-89 (ICC: 0.38, 0.41, 0.39 respectively) and moderate agreement for GFR ≥90 ml/min/1.73m2 (ICC: 0.55).
Conclusion: These findings suggest that the 2009 CKD-EPI equation still performs better than the 2021 CKD-EPI equation without the race co-efficient, especially in higher GFR ranges for people with diabetes.

Disclosure
R. Kwok: None. R. MacIsaac: None. K. Kishore: None. T. Zafari: None. M. Hachem: None. D. Koye: None. E. Schaeffner: Consultant; AstraZeneca. Other Relationship; National Kidney Foundation. T. Jeong: None. W. Min: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. L. Churilov: None. E.I. Ekinci: Advisory Panel; Lilly Diabetes. Research Support; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company. Board Member; Eli Lilly and Company. Advisory Panel; Abbott. Research Support; Endogenex, Versanis, AstraZeneca.

Funding
Australian Government Research Training Program (RTP) Scholarship
428-P: Discordance between Hemoglobin A1c and CGM-Assessed Glycemia in CKD
Authors: TANG MENGYAO , DE BOER IAN , KALIM SAHIR 
Published: June 2024

Background: Hemoglobin A1C’s accuracy and precision decrease in CKD, and there is an increased interest in using CGM as an alternative method for glycemic monitoring. However, most CGM data stems from type 1 or insulin-treated type 2 diabetes (T2D) patients with normal eGFR. We conducted a pilot study to evaluate CGM metrics in CKD, including patients with T2D not using insulin and those without diabetes.
Methods: We enrolled 10 CKD patients (6 with T2D and 4 without diabetes) who wore blinded CGM (DexCom G6) for 20 days. A1C was measured at the end. Discordance was defined as an absolute difference between A1C and glucose management indicator (GMI) &gt;=0.5%.
Results: Participants had a mean age of 68 and mean eGFR was 35 mL/min/1.73m². In participants with T2D (A1C range: 5.4-6.9%), there was wide range of CGM metrics: range of mean glucose was 115-215mg/dL, GMI 6.1-8.4%, CV 16-29%, TIR 13-96%. In participants without diabetes (A1C range: 5.2-6.1%), the range of mean glucose was 117-158mg/dL, GMI 6.1-7.1%, CV 16-29%, time-in-tight-range (70-140mg/dL) 37-86%. For several participants with similar A1C values, glycemic patterns differed substantially. Seven (70%) participants had A1C-GMI discordance, with A1C underestimating GMI (Fig).
Conclusion: Among CKD patients, large variations in CGM metrics existed and A1C-GMI discordance was common. Our findings warrant further investigation into the prevalence and predictors of such discordance.

Disclosure
M. Tang: Research Support; Dexcom, Inc. I. de Boer: Consultant; Boehringer-Ingelheim, Lilly Diabetes, AstraZeneca, Novo Nordisk, Alnylam Pharmaceuticals, Inc., George Clinical. Research Support; Dexcom, Inc., Novo Nordisk. S. Kalim: Advisory Panel; Alnylam. Speaker's Bureau; Fresenius Kabi.

Funding
American Heart Association (23POST1010825); DexCom (IIS-2023-007)
436-P: Stringent Glycemic Control and Long-Term Macrovascular Outcomes in People with Type 2 Diabetes in China—A Retrospective Study
Authors: PAN QI , SUN FENG , ZHANG MENG , SHEN PENG , SUN YEXIANG , LIN HONGBO , ZHAN SIYAN , GUO LIXIN 
Published: June 2024

Introduction & Objective: Safely achieving stringent glycemic control at hemoglobin A1c (HbA1c) ≤ 6.5% is recommended in some diabetes guidelines, and HbA1c &lt; 5.7% is considered a normal level. We aim to examine the association between stringent glycemic control and long-term macrovascular outcomes using real world data in China.
Methods: Data were retrospectively extracted from a regional data platform (2006/1/1-2021/10/31) in Yinzhou, Ningbo, China. Adult T2D patients with ≥ 1 HbA1c record from 2007/01/01-2016/10/31 were included to ensure ≥ 5 years of follow-up. Index date was the first HbA1c occurred ≥ 90 days after the initial T2D diagnosis. Index and sustained stringent glycemic control were defined as achieving HbA1c at ≤ 6.5% or &lt; 5.7% at index or every measurement during follow-up, respectively. Cox proportional hazard model was used to examine the association between stringent glycemic control and 3-point major adverse cardiovascular event (3P-MACE) occurred during follow-up, adjusting for demographic and clinical characteristics.
Results: A total of 7,049 patients (mean age 61.4±11.4 years, 3,751 [53.7%] female) were analyzed. Over a median follow-up of 6.7 years (interquartile range 5.5-7.9), 3P-MACE occurred in 1565 (22.2%) patients at an incidence rate of 3.4 per 100 person-years. Index and sustained stringent glycemic control were significantly associated with 3P-MACE risk reduction (all p&lt;0.05). For index stringent glycemic control, the adjusted hazard ratio (aHR) was 0.88 [0.79-0.98] for HbA1c ≤ 6.5% and 0.84 [0.70-1.00] for HbA1c &lt; 5.7%. For sustained stringent glycemic control, the aHR was 0.74 [0.63-0.86] for HbA1c ≤ 6.5% and 0.58 [0.42-0.79] for HbA1c &lt; 5.7%.
Conclusion: Stringent glycemic control was associated with significant risk reduction in long-term macrovascular outcomes in Chinese people with T2D. Intensive diabetes therapies may have long-term benefits for cardio-cerebrovascular outcomes in T2D patients.

Disclosure
Q. Pan: None. F. Sun: None. M. Zhang: None. P. Shen: None. Y. Sun: None. H. Lin: None. S. Zhan: None. L. Guo: Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Hengrui (USA) Ltd., Dreisamtech, Dongbao, Gan & Lee, Hansoh.

Funding
Eli Lilly and Company, Shanghai, China
437-P: Three Decades of Lipid-Lowering Therapy in Type 2 Diabetic Patients with Angiographically Proven Stable Coronary Artery Disease
Authors: VOGEL JOHANNES , RATZ MAGDALENA , ELSNER PASCAL , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend&lt;0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend&lt;0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend&lt;0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend&lt;0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend&lt;0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of &lt;55 mg/dL (ptrend&lt;0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Disclosure
J. Vogel: None. M. Ratz: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
444-P: Machine Learning Driven Prediction of Hyperglycemia, Acute Kidney Injury, and Atrial Fibrillation after Cardiac Surgery Using High-Resolution Metabolomics
Authors: KU DOHYUN , SAM VARGHESE JITHIN , SMITH MATTHEW R. , PEREZ-GUZMAN MIREYA , GUERRERO ARROYO LIZDA I. , BARTELT JACKSON , ZAHEDI TAJRISHI FARBOD , LI JING , PASQUEL FRANCISCO J. 
Published: June 2024

Stress hyperglycemia (SH), acute kidney injury (AKI), and atrial fibrillation (AF) are common complications after cardiac surgery. We examined the predictive value of metabolite changes on inpatient outcomes in participants undergoing coronary artery bypass graft surgery. Methods: We analyzed 8,631 and 10,919 metabolites from C18 chromatography and hydrophilic interaction liquid chromatography (HILIC) to predict SH, AKI, and AF. The study included 61 participants (mean age: 62.5; 16.1% female) with one missing SH. We imputed zero values in the metabolites with half the minimum value. For SH and AF, we utilized the log-ratios of metabolite measured during and before surgery as features, while for AKI, we employed those measured exclusively during surgery. We used the Mann-Whitney U-test to select significant features and the Partial Least Squares (PLS) regression for dimension reduction. PLS components, along with covariates such as age, sex, and BMI, were incorporated into machine learning (ML) classifiers, and the Random Forest classifier emerged as the most effective based on leave-one-out cross-validation (LOOCV) performance. Finally, we aggregated significant feature contributions across all LOOCV iterations to identify the most influential features.
Results: To predict SH, our ML pipeline achieved an AUC of 0.82, accuracy of 0.77, sensitivity of 0.84, and specificity of 0.71 identifying five significant features across all LOOCV iterations. For AF prediction, we achieved an AUC of 0.85, accuracy of 0.82, sensitivity of 0.91, and specificity of 0.77, with 97 significant features identified. For AKI, we attained an AUC of 0.74, accuracy of 0.72, sensitivity of 0.79, and specificity of 0.70 identifying 20 significant features.
Conclusion: Machine learning algorithms may aid in the identification of multiple potentially relevant biomarkers linked to adverse cardiometabolic outcomes after cardiac surgery.

Disclosure
D. Ku: None. J. Varghese: None. M.R. Smith: None. M. Perez-Guzman: None. L.I. Guerrero Arroyo: None. J. Bartelt: None. F. Zahedi Tajrishi: None. J. Li: None. F.J. Pasquel: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Ideal Medical Technologies, Novo Nordisk. Consultant; Dexcom, Inc., Medscape.

Funding
National Institutes of Health (K23GM128221)
448-P: The A Body Shape Index and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events In Patients with Established Coronary Artery Disease
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2024

The A Body Shape index (ABSI) is a validated measure of visceral adiposity that is calculated based on waist circumference, height and BMI. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in a cohort of 938 patients with CAD over a mean follow-up time of 8.1±4.2 years. At baseline, the ABSI was higher in patients with type 2 diabetes (T2DM; n=308) than in those who did not have diabetes (8.4±0.6 vs. 8.3±0.5; p=0.032). Prospectively, the ABSI significantly predicted the incidence of cardiovascular events (n=389) after adjustment for age, gender, smoking, hypertension, LDL cholesterol, HDL cholesterol, and T2DM (standardized adjusted HRs 1.12 [1.03-1.22]; p=0.009, respectively). T2DM in turn also significantly predicted cardiovascular events in this model with a HR of 1.23 [1.02-1.49]; p=0.034 after adjustment for ABSI.
We conclude that ABSI and T2DM are mutually independent risk factors for cardiovascular events in patients with established 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.