bluuebunny/crossref_metadata_2025_split huggingface dataset:
315-OR: Task-Induced Alterations in the Salience Network amongst Patients with Type 1 Diabetes
Authors: SANCHEZ RANGEL ELIZABETH , BELFORT-DEAGUIAR RENATA , LACADIE CHERYL , CHUNG TAMMY J. , SCHEINOST DUSTIN , MASON GRAEME F. , HWANG JANICE J. 
Published: June 2024

Introduction & Objective: Patients with Type 1 Diabetes (T1D) have altered brain functional connectivity (FC) at resting state, particularly in attention and decision-making brain regions. Recent studies have shown that assessing FC during a cognitive task may be more predictive of individual traits and function. In this study, we investigate how FC within the salience network (SAL), which integrates brain responses to external stimuli, is altered when patients with T1D perform cognitive tasks during euglycemia and mild hypoglycemia.
Method: Thirty-one subjects (20 T1D, 11M/9F, age 37 ± 13 yrs; BMI 27.4 ± 5.4 HbA1c 7.6 ± 0.9 %) and (11 HC, 4M/7F, age 30 ± 8 yrs; BMI 24.9 ± 2.9, HbA1c ± 5.3 ± 0.3%) completed a 2-step hyperinsulinemic-euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp both at rest and during three tasks: 2-back  (working memory), card guess (reward), and gradual-onset continuous performance (gradCPT; sustained attention). After standard preprocessing, pairwise FC between the nodes of the Salience (SAL) network (Left and Right anterior insula, dorsal anterior cingulate cortex) was calculated. FC in the SAL network was defined as the average of these pairwise values.
Results: Patients with T1D had lower FC during hypoglycemia in the SAL network compared to HC during resting state (P&lt;0.009) as well as 2-back (P&lt;0.024), Card Guess (P&lt;0.036), and gradCPT (P&lt;0.036) tasks. There were no significant relationships between FC and counterregulatory hormones.
Conclusion: Compared to HC, patients with T1D have lower FC in the SAL network during mild hypoglycemia while performing memory, attention and reward stimulating cognitive tasks. These findings suggest an important role for the SAL network in integrating brain responses during hypoglycemia.

Disclosure
E. Sanchez Rangel: None. R. Belfort-DeAguiar: Research Support; Fractyl Health, Inc. C. Lacadie: None. T.J. Chung: None. D. Scheinost: None. G.F. Mason: Consultant; Merck & Co., Inc. J.J. Hwang: None.

Funding
National Institutes of Health (R01DK123227)
32-PUB: Glycemic Variability after Initiation of SGLT2 Inhibitors in CKD
Authors: TANG MENGYAO , DE BOER IAN , KALIM SAHIR 
Published: June 2024

Background: SGLT2 inhibitors (SGLT2i) are widely used for cardiorenal protection in CKD patients, irrespective of diabetes. While their effect on A1C is smaller with lower eGFR, the impact of SGLT2i initiation on short-term glycemic variability is unclear.
Methods: In a pilot study, we enrolled 11 CKD patients with clinical indications for SGLT2i -7 with type 2 diabetes not on insulin, and 4 without diabetes. Participants wore DexCom G6 CGM for 10 days pre-SGLT2i and another 10 days post-SGLT2i initiation. Linear mixed-effects models with random intercepts were used to analyze glycemic variability, assessed by the hourly coefficient of variation (CV).
Results: The mean age of participants was 68 years, with 82% male, mean eGFR of 38 mL/min/1.73m², and median albuminuria of 347 mg/g. Mean A1C levels were 6.6% in participants with diabetes and 5.5% in those without. Nine participants received empagliflozin 10mg, two dapagliflozin 10mg. Following SGLT2i initiation, participants with diabetes showed no significant change in mean glucose (160±54 vs 155±50 mg/dL, p=0.52), GMI (7.1±1.3 vs 7.0±1.2, p=0.52), or TIR (67±37 vs 69±39%, p=0.66). There was no change in time above range or time below range. Only 1 participant on GLP-1 receptor agonist developed asymptomatic level 1 hypoglycemia. Similarly, patients without diabetes had no change in any of the previously mentioned CGM metrics. However, glycemic variability decreased post-SGLT2i initiation, as shown by hourly CV reductions (-0.40±0.13, p=0.002). The magnitude of hourly CV reduction was more pronounced in participants without diabetes compared to those with diabetes (p-interaction=0.002). Despite higher hourly CV during daytime than nighttime, the impact of SGLT2i initiation on CV was similar across time periods without significant interaction by time of day.
Conclusion: After SGLT2i initiation in CKD, while mean glycemia and TIR remained unchanged, glycemic variability diminished. This finding warrants further investigation in a larger study.

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)
323-OR: Genetic Basis of Diabetic Macular Edema and Proliferative Diabetic Retinopathy—Insights from Next Generation Sequencing in the DRGen Study
Authors: RANGASAMY SAMPATH , GENOMICS GROUP TGEN , MONICKARAJ FINNY , SUN JENNIFER K. , AIELLO LLOYD P. , DAS ARUP 
Published: June 2024

Introduction & Objective: Our prior research has shown a clear distinction between two types of diabetic retinopathy (DR): predominantly exudative diabetic macular edema (DME) and predominantly proliferative diabetic retinopathy (PDR). These clinical presentations often occur separately, with a large percentage of patients (85% for PDR, 80% for DME) not showing signs of the other type. This suggests that DME and PDR may not be a single disease entity that progresses linearly but rather distinct diseases driven by different molecular mechanisms and genetic factors.
Methods: We analyzed two distinct patient groups: i) only PDR and no signs of DME (n=182), and the other with only center-involving DME and no PDR (n =77). The severity of PDR was graded using the ETDRS standard protocol on ultrawide field retinal images. Whole-exome and whole-genome sequencing were performed to identify genetic factors, and a novel algorithm was used to evaluate the impact of coding variants in the cohort.
Results: Comparative analysis of patients with exclusive manifestations of PDR compared to DME revealed a unique genetic framework differentiating the two cohorts. Notably, the prevalence of rare functional variants was significantly elevated in the PDR group (p&lt;0.05). We discovered functional variants in genes, including CD36, MMRN2, EPHB2, PLAUR, and RAPGEF3, which are enriched in the angiogenesis pathway. Phenotype-centric gene variant analysis underscored the role of MMRN2, a key player in angiogenesis (p&lt;0.001). MMRN2 (Multimerin-2) is a crucial regulator of endothelial cell movement, functioning as a negative modulator of angiogenesis by inhibiting KDR activation through its interaction with VEGFA.
Conclusions: Rare functional variants may act as phenotype modifiers, potentially modulating the trajectory of DR into DME or PDR. Functional validation of these factors could represent new biomarkers and therapeutic targets for DR.

Disclosure
S. Rangasamy: None. F. Monickaraj: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. A. Das: None.

Funding
5R01EY028606
367-P: Clinical Characteristics of Type 1 Diabetes and Severe Hypoglycemia in Adult Continuous Glucose Monitor Users
Authors: CALLAHAN PATRICK , BOATENG-KUFFOUR ADRIANA , CHANDARANA KEVAL , GUPTA TINA , CHEN LIANG , KELLY CAITLIN S. , NGUYEN HUYEN , CHAPMAN KATHERINE S.M. , CORNELIUS EMILEE M. , WOLF WENDY , POLONSKY WILLIAM H. 
Published: June 2024

Introduction & Objective: Recurrent severe hypoglycemic events (SHE) are associated with impaired awareness of hypoglycemia (IAH). This study describes the demographic and clinical characteristics of adults with type 1 diabetes (T1D) and SHE/IAH.
Methods: Adult (≥18 years) continuous glucose monitor (CGM) users from the T1D Exchange Registry with self-reported T1D diagnosis ≥5 years completed an online survey with clinical and demographic characteristics. SHE cohorts were created based on SHE frequency in the past 12 months and the presence/absence of IAH (Modified Gold Score): problematic SHE (2+ SHE/IAH-; 1+ SHE/IAH+) and no SHE (0 SHE/IAH+; 0 SHE/IAH-). Participant characteristics were descriptively summarized (mean, standard deviation [SD]).
Results: A total of 1,847 T1D CGM users responded. The problematic SHE cohort (n=375) compared with the no SHE cohort (n=1,033) were older (age 49.0 vs. 45.6 years), more racially diverse (86.4% vs. 92.7% Caucasian), had lower levels of employment (58.4% vs. 71.2%), increased report of lower income &lt;$50,000 (25.1% vs. 16.9%), and more often reported Medicaid as their primary health insurance (10.4% vs. 3.1%). The problematic SHE cohort reported longer duration of T1D (31.9 [SD 16.0] vs. no SHE 28.6 [SD 14.8]), lower insulin pump use (78.4% vs. 85.9%), slightly higher recent HbA1c (6.9 [SD 1.1] vs. 6.6 [SD 0.9]), with more participants with HbA1c ≥7% (42.4% vs. 31.3%). More T1D-related complications were reported in the problematic SHE vs. no SHE cohort (retinopathy 28.3% vs. 21.5%; neuropathy 24.5% vs. 10.5%; nephropathy 8.3% vs. 4.5%; gastroparesis 19.5% vs. 6.5%; and cardiovascular disease 12.5% vs. 5.5%). Based on BMI calculated from reported height and weight, &gt;60% of participants were overweight or obese across all cohorts.
Conclusion: Findings suggest those who experience SHE have higher clinical burden and lower socioeconomic status, highlighting the need for innovative approaches to management for these individuals.

Disclosure
P. Callahan: Employee; Vertex Pharmaceuticals Incorporated. A. Boateng-Kuffour: Employee; Vertex Pharmaceuticals Incorporated. K. Chandarana: Employee; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Vertex Pharmaceuticals Incorporated, Novo Nordisk, Eli Lilly and Company. T. Gupta: Employee; Vertex Pharmaceuticals Incorporated. L. Chen: None. C.S. Kelly: None. H. Nguyen: None. K.S.M. Chapman: None. E.M. Cornelius: None. W. Wolf: None. W.H. Polonsky: Research Support; Abbott Diagnostics, Dexcom, Inc. Consultant; Eli Lilly and Company, Sanofi. Advisory Panel; embecta. Consultant; Vertex Pharmaceuticals Incorporated. Advisory Panel; 9am Health.

Funding
Vertex Pharmaceuticals Incorporated
385-P: MDSC-Mediated Neutrophil Extracellular Traps–Based Targeting of Diabetic Vasculopathy—Dapagliflozin for Vascular Remodeling in Diabetic Nephropathy
Authors: CHEN KEYU , GAO ZEZHENG , WANG HAN , CHENG TANG , LI XIUYANG 
Published: June 2024

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide, and its pathogenetic mechanism is closely associated with vascular endothelial dysfunction. Myeloid-derived suppressor cells (MDSCs) recently have been found to be participated in diabetic microangiopathy, especially DN, which can promote beneficial vascular remodeling by releasing neutrophil extracellular traps (NETs) and removing senescent vascular endothelium. Therefore, targeting MDSC-NETs may also be an important mechanism for dapagliflozin to ameliorate DN. Focusing on this mechanism, based on the KKay mice model of spontaneous DN, we combined phenotyping and electron microscopy to obtain the evidence that dapagliflozin was effective in ameliorating urine albumin creatine ratio and the structural damage of glomerular vascular endothelium.Then through immunohistochemistry, flow cytometry, quantitative cytokine antibody array, metabolomics, proteomics, and other multi-omics correlation analyses, to find that dapagliflozin significantly increased M-MDSC and PMN-MDSC levels in the peripheral blood of KKay mice. Dapagliflozin was found to improve glomerular endothelial function and hemodynamics by NETs-formatting, leukocyte transendothelial migration, complement and coagulation cascades, VEGF-JAK-STAT3 pathway, and reduced vascular-related pro-inflammatory cytokines such as CCL4, IL-22, IL23, TREM-1, CCL17, IGFBP5, and TGFb1. Meanwhile, dapagliflozin regulates the metabolism of amino acids and phospholipids represented by L-glutamine and phosphatidylcholine in renal tissues, attenuates the metabolic inflammatory state of glomerular endothelium, and promotes vascular repair and remodeling.

Disclosure
K. Chen: None. Z. Gao: None. H. Wang: None. T. Cheng: None. X. Li: None.
4-OR: Fat Contents in Pancreatic Body and Liver Are Synergistic Risk Factors for Impaired Glucose Regulation in PCOS
Authors: SHAN CHANG , YU JIE , ZHU YU-CHEN , ZHAO JIAN , WANG LI-HUI , LI YU-SHAN , LIN SI-YU , LIU WEI , LU QING , TAO TAO 
Published: June 2024

Introduction & Objective: Women with polycystic ovary syndrome (PCOS) are more prone to glucose metabolic abnormalities, which is thought to be related to increased visceral adiposity. This study aimed to evaluate the relationship between fat deposition in the pancreas and liver and glucose metabolism in PCOS.
Methods: This study included 160 women with PCOS diagnosed according to the Rotterdam 2003 criteria between April 2019 and September 2022. All participants underwent the anthropometric and biochemical assessments including an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat deposition in the pancreas and liver.
Results: Pancreatic interlobular fat volume, pancreatic body fat content and liver fat content were significantly higher in PCOS with diabetes than normal glucose tolerance (P &lt; 0.05). Increased pancreatic body fat [OR 2.21 (95% CI 1.01 - 4.85), P = 0.047] and hepatic average fat [OR 2.92 (95% CI 1.13 - 7.51), P = 0.026] were independently associated with higher risks for impaired glucose regulation (IGR). Patients with high pancreatic body fat and high hepatic average fat had increased risk for IGR after multiple confounding adjustments [OR 5.49 (95% CI 1.63 - 18.47), P = 0.006]. Combining pancreatic body fat and hepatic average fat with age, BMI, WHR, TG and FAI, the AUC for predicting IGR in PCOS was 0.789 with a sensitivity of 0.713 and a specificity of 0.800.
Conclusion: Fat contents in the pancreatic body and liver are synergistic risk factors for IGR in PCOS.

Disclosure
C. Shan: None. J. Yu: None. Y. Zhu: None. J. Zhao: None. L. Wang: None. Y. Li: None. S. Lin: None. W. Liu: None. Q. Lu: None. T. Tao: None.

Funding
National Natural Science Foundation of China (82170807, 82370797); the Natural Science Foundation of Shanghai (12ZR1417800); the Shanghai Sailing Program (21YF1425300); the National Nature Promotion Project, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (RJTJ23-ZD-005); the Bethune Charitable Foundation (J202103E006); the Shanghai Medical and Health Development Foundation (SHMHDF DMRFP_II_10) and the Medical Guidance Science and Technology Support Projects of Shanghai Municipal Science and Technology Commission (18411968700).
416-P: Variability of Metabolic Risk Factors for Kidney Function Decline in Diabetes Compared with Nondiabetes—A Cluster Analysis of Community-Based Prospective Cohort Study
Authors: RYANG SOREE , MI KIM JEONG , IM MYUNGSOO , KIM DOOHWA , AH YOON SANG , KIM JINMI , SOO KIM SANG 
Published: June 2024

Introduction & Objective: We aimed to identify different patterns of estimated glomerular filtration rate (eGFR) trajectories depending on diabetes status using long-term prospective cohort and to find the association and variability between risk factors, and patterns of eGFR trajectories.
Methods: At baseline, 2,084 participants were recruited from the Korean Genome and Epidemiology Study, followed up for 10 years. We divided participants into two groups based on their diabetes status. We used clustering trajectory analysis to identify different eGFR trajectory patterns and used logistic regression to identify association between trajectories and variability of chronic kidney disease (CKD) risk factors.
Results: We identified four distinct patterns of eGFR trajectories. About 4% of participants were belonged to rapid eGFR decline cluster, with more rapid decline rate compared to nondiabetes group. In diabetes group, systolic blood pressure (sBP) was associated with rapid eGFR decline at cross-sectional and longitudinal analysis (OR 2.58 [95% CI 1.07-6.23], p=0.035 and 3.34 [95% CI 1.03-6.02], p=0.043).
Conclusion: There was a difference in rate of kidney function decline according to diabetes status. Among CKD risk factors, sBP was important risk factor for rapid eGFR decline aspect baseline and variability in diabetes.

Disclosure
S. Ryang: None. J. Kim: None. M. Im: None. D. Kim: None. S. Yoon: None. J. Kim: None. S. Kim: None.

Funding
Korean Diabetes Association and National Research Foundation of Korea (2019F-8)
422-P: Ferritin and COVID-19 among Dialysis Patients with Diabetes
Authors: QUANDELACY TALIA , HU MING , WANG YUEDONG , KOTANKO PETER , CONWAY REBECCA B. 
Published: June 2024

Early in the COVID-19 pandemic, severe hyperferritinemia, independent of inflammation, manifested as a laboratory characteristic prognostic of poor COVID-19 outcomes, including death. To determine the association between ferritin and COVID-19 infection, hospitalization and mortality in dialysis patients w/ diabetes, we followed 114,881 in-center hemodialysis patients w/ diabetes from January 2020 to March 2022. For incident COVID infection, average ferritin levels from one year to two weeks prior to RT-PCR determined COVID-infection (days-365,-14) were used as baseline. Change in ferritin was defined as the difference between the baseline average and two weeks prior average (-14,0) to the PCR positive test date. For non-infected patients, a PCR test date was randomly chosen. Logistic regression assessed the association of ferritin and change in ferritin w/ COVID-19 infection, hospitalization and mortality, adjusting for age, sex, race, vaccination status, vintage, and lab values. During follow-up, the cumulative incidence or COVID-19 was 23%; in the infected, 33% of the population was hospitalized and 11% died. In multivariable adjusted analysis, higher baseline ferritin (p&lt;0.01) and change in ferritin (p&lt;0.001) were linked w/ increased risk of COVID-19 infection. However, in the infected, neither baseline (p=0.13) nor change in ferritin (p=0.07) were linked w/ hospitalization. Positive change in ferritin, but not baseline ferritin (p=0.85), showed a trend towards an increased mortality risk (p=0.06). Other significant clinical risk factors were lower hgb (p&lt;0.001) for COVID-19, higher baseline NLR (p&lt;0.05) and not being vaccinated (p&lt;0.001) for hospitalization, and higher neutrophil to lymphocyte ratio (&lt;0.001) for mortality. Our data suggest baseline and rise in ferritin are associated w/ risk of COVID-19 but show a weaker relationship w/ hospitalization and death. NLR, which is also indicative of inflammation, is a stronger risk factor for hospitalization and mortality in patients w/ diabetes.

Disclosure
T. Quandelacy: None. M. Hu: None. Y. Wang: None. P. Kotanko: Other Relationship; Fresenius Medical Care. R.B. Conway: None.
424-P: Persons with Type 2 Diabetes Who Had Macroalbuminuria Prior to Impaired Glomerular Filtration Exhibited Increased Arteriolar Hyalinosis
Authors: SUZUKI AKIHIKO , MORIYA TATSUMI , MATSUBARA MADOKA , HAYASHI AKINORI , MIYATSUKA TAKESHI 
Published: June 2024

There is a certain number of people with diabetes who have decreased GFR without albuminuria. Diabetic kidney disease is comprehensive concept including typical and atypical diabetic nephropathy including such cases. However, it is still unknown which histological parameters precisely predict increased albuminuria or reduced GFR in persons with type 2 diabetes. To address this, we hypothesized that index of arteriolar hyalinosis (IAH) could be a predictor for onset of macroalbuminuria and eGFR&lt;60 mL/min/1.73 m2 (chronic kidney disease, CKD) during early diabetic nephropathy. The subjects consisted of 34 persons with type 2 diabetes (22 men; age, 46±9 years; eGFR 92.4±18.2 mL/min/1.73 m2, 17 normoalbuminuria, 17 microalbuminuria) who underwent percutaneous renal biopsy. These subjects were divided into 3 groups, onset of macroalbuminuria in advance (MA; n=9), onset of eGFR&lt;60 in advance (G; n=8) and no onset of CKD (C; n=17) during the observation period (19±6 year). Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes. There was no difference in age, sex, duration of diabetes, HbA1c, eGFR, blood pressures at the baseline among 3 groups. Urinary albumin was significantly increased in MA than G and C groups (p=0.034, 0.001, respectively). The IAH was significantly larger in MA (1.95±0.70) than G (1.41±0.44, p=0.049) and C (1.37±0.49, p=0.014) groups while other histological parameters did not reach significant extent. The logistic analysis indicated that IAH score and urinary albumin are associated with MA (p=0.028 and p=0.015, respectively). Multiple regression analysis revealed that arteriolar hyalinosis (p=0.042) and urinary albumin (p=0.025) were associated with MA group.
In conclusion, persons with type 2 diabetes having macroalbuminuria prior to reduced GFR tend to have arteriolar hyalinosis at the baseline.

Disclosure
A. Suzuki: None. T. Moriya: None. M. Matsubara: None. A. Hayashi: None. T. Miyatsuka: None.
427-P: Influence of Blood Pressure Management on the Renal Outcome in Patients Treated with SGLT2 Inhibitors and GLP1 Receptor Agonist
Authors: KOBAYASHI KAZUO , TOYODA MASAO , KAWANAMI DAIJI , TAMURA KOUICHI 
Published: June 2024

Background: Both sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1Ras) showed robust evidences for not only cardiovascular but also renal outcomes and the combination treatment of these drugs is increasing in clinical practice. We previously reported that the preceding drug did not influence the renal outcomes in patients with these combination treatments. We also reported the importance of post blood pressure (BP) management for the renal outcomes in SGLT2i-treated patients, however, it is poorly surveyed in patients with the combination treatment.
Method: A retrospective study was conducted in 418 patients who were treated with both SGLT2i and GLP1Ra. The progression of the albuminuria stage, the eGFR decline of ≥30%, or both were defined as the renal composite outcome. The cut off value of post-treatment mean arterial pressure (post-MAP) were calculated using receiver ROC curve analysis. The patients were divided into two groups by the cut-off value and propensity score (PS) matching method was performed for comparisons between the two groups.
Results: The calculated cutoff value of post-MAP was 87.3 mmHg and the patients were divided into two groups: 281 patients in post-MAP≥87.3 group and 137 patients in post-MAP&lt;87.3 group. Of the 111 PS-matched patients in each group, the renal composite outcome after the combination treatment was observed in 38 patients (34.2%) in post-MAP≥87.3 group, which was significantly higher than in 18 patients (17.1%) in post-MAP&lt;87.3 group (p=0.005). The progression of albuminuria stage was significantly more frequent in post-MAP≥87.3 group (23.4%) than post-MAP&lt;87.3 group (8.1%) (p=0.004), however no significant difference was observed for the eGFR decline of ≥30%.
Conclusion: Poor BP management after combination treatment of SGLT2i and GLP1Ra treatment worsened the renal composite outcomes, especially the progression of albuminuria stage.

Disclosure
K. Kobayashi: None. M. Toyoda: None. D. Kawanami: None. K. Tamura: None.