bluuebunny/crossref_metadata_2025_split huggingface dataset:
177-OR: Time Below Range (TBR) and Its Link to Impaired Awareness of Hypoglycemia (IAH) and Severe Hypoglycemia (SH)—Evidence from the Association of British Clinical Diabetologists (ABCD) Study
Authors: DESHMUKH HARSHAL , WILMOT EMMA G. , CHOUDHARY PRATIK , CULL MELISSA L. , RYDER ROBERT E. , SATHYAPALAN THOZHUKAT , WALTON CHRISTOPHER 
Published: June 2024

Objectives: The primary objective of this study was to explore the relationship between the Time Below Range (TBR) and Impaired Awareness of Hypoglycemia (IAH) and Severe Hypoglycemia (SH).
Methods: Our study used data from people with diabetes using isCGM in the ABCD audit. Hypoglycemia awareness was evaluated using the Gold score, with a score of ≥4 denoting Impaired Awareness of Hypoglycemia (IAH). SH was defined as hypoglycemia necessitating third-party assistance. Logistic regression analysis was used to identify the association between TBR% (&lt;70 mg/dl) at the last follow-up (used as a continuous independent variable) and follow-up Gold score and the number of SH between isCGM initiation and follow-up. Youden’s J index was used to identify the optimal TBR% cutoffs for detecting IAH and SH.
Results: The study consisted of 15,777 people with diabetes with at least one follow-up, of which TBR data was available for 5030 people. The median TBR% in the study population was 4% (IQR 2%-6.6%). Following adjustment for age, gender, and BMI, TBR was significantly associated with both SH (Beta=0.02 P=0.001) and IAH (Beta=0.01 P=0.006). The determined optimal TBR cutoffs for identifying follow-up IAH and SH were 3.35% and 3.95%, respectively. These cutoffs yielded sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 65%, 43%, 19%, and 85% for IAH and 73%, 42%, 5%, and 97% for SH.
Conclusion: Our study, based on real-world data, shows a clear association between TBR% and IAH and SH in people with diabetes. Our findings broadly align with the international consensus recommending a TBR of &lt;4% in individuals with type 1 diabetes. However, we observed that this cutoff has limited discriminatory power in predicting SH and IAH, emphasising the need for nuanced approaches in establishing optimal TBR thresholds for distinct diabetes-related outcomes.

Disclosure
H. Deshmukh: None. E.G. Wilmot: Other Relationship; Abbott. Speaker's Bureau; AstraZeneca. Other Relationship; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, embecta, Medtronic, Novo Nordisk. Advisory Panel; Roche Diabetes Care. Other Relationship; Sanofi. Speaker's Bureau; Ypsomed AG. P. Choudhary: Advisory Panel; Abbott, Biolinq. Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. Advisory Panel; Ypsomed AG, Vertex Pharmaceuticals Incorporated. M.L. Cull: None. R.E. Ryder: Speaker's Bureau; Abbott, Besins Healtcare, BioQuest, GI Dynamics. Consultant; GI Dynamics. Other Relationship; Novo Nordisk. T. Sathyapalan: Research Support; Abbott. Advisory Panel; Rhythm Pharmaceuticals, Inc., Pfizer Inc. C. Walton: None.
1772-P: Monocarbonyl Analogs of Curcumin C66 and B2BrBC Modulate Diabetes-Related Gene Expression in Rat Pancreatic Cells
Authors: STOJCHEVSKI RADOSLAV , BOGDANOV JANE B. , HADZI-PETRUSHEV NIKOLA , MLADENOV MITKO , PORETSKY LEONID , AVTANSKI DIMITER 
Published: June 2024

Monocarbonyl analogs of curcumin (MACs) lacking a β-diketone moiety have been shown to exhibit improved stability and better bioavailability than curcumin. This study aimed to evaluate the effects of two MACs (C66 and B2BrBC) on the expression of genes related to the onset, development, and progression of diabetes in rat pancreatic RIN-m cells. The cells were cultured in complete RPMI 1640 medium and treated with C66 or B2BrBC (50 μM) or vehicle for 72 h, followed by treatment with streptozotocin (STZ) (1.5 mM) or vehicle for an additional 24 h. Quantitative PCR array analysis was performed using a rat diabetes panel comprising 84 genes. The data demonstrated that C66 and B2BrBC significantly modulated the expression of 16 genes involved in growth regulation in RIN-m cells and genes associated with inflammation, immune response, and energy metabolism. Notably, C66 and B2BrBC inhibited the STZ-induced expression of pro-inflammatory Tnf and Icam1 while increasing the expression of Ins1. Moreover, C66 pretreatment influenced Ctla4 and Serpine1 expression, and B2BrBC pretreatment affected Mapk8, Serpine1, and Igfbp5 levels compared to STZ treatment alone. Cells treated with MACs and STZ showed a different pattern of gene expression for Igfbp5, Gpd1, Agt, Serpine1, Cebpa, Retn, Ccl5, and Srebf1 compared to vehicle-treated cells. Our findings show that C66 and B2BrBC modulate the expression of essential diabetes-related genes, which may serve as a basis for further research on MACs and contribute to the development of novel therapeutic targets and strategies.

Disclosure
R. Stojchevski: None. J.B. Bogdanov: None. N. Hadzi-Petrushev: None. M. Mladenov: None. L. Poretsky: None. D. Avtanski: None.

Funding
Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research
1775-LB: Role for Glucagon-Like Peptide 1 Receptor Agonists in Symptomatic Post-bariatric Hypoglycemia
Authors: ALQAZLAN TAMIM , ALSAEED ASEEL A. , OTHMAN TAREQ T. , ALSHEHRI ALI , ALMEHTHEL MOHAMMED 
Published: June 2024

Introduction & Objectives: Post-bariatric surgery patients suffer from weight gain and hypoglycemia. Role of GLP-1 in such patients is not established. We studied the effects of GLP-1 agonists on hypoglycemia, weight and hypoglycemic attitudes and behavior among patients who had bariatric surgery.
Methods: In a cross-sectional study, conducted at a Medical City in Saudi Arabia, adult patients who underwent bariatric surgery and prescribed GLP-1 agonist were included. Data were collected on socio-demographic, medical history, weight, BMI, hypoglycemic episodes, and Hypoglycemic Attitudes and Behavior Scale (HABS). Wilcoxon Ranked Sum, McNemar and test of homogeneity were used to assess the differences before and after the GLP-1.
Results: Out of 21 patients included in the analysis, 33% were male and 48% had diabetes. Vertical sleeve gastrectomy (62%) was the most common procedure. Liraglutide was most common GLP-1 analog used. There was significant reduction in the weight and BMI. In the HABS, except the domain of confidence, other domains remained unchanged post GLP-1. Hypoglycemia episodes per week also showed significant change after GLP-1. Symptoms of hypoglycemia did not change significantly. (Table 1)
Conclusions: In this study, use of GLP-1 was found to have positive impact on weight and hypoglycemia among bariatric surgery patients. Large scale studies are needed to generate more robust evidence.

Disclosure
T. AlQazlan: None. A.A. AlSaeed: None. T.T. Othman: None. A. Alshehri: None. M. Almehthel: None.
1776-LB: Hyperglycemia Stimulates Local Lactate Production in the Hypothalamus
Authors: UZO CHUKWUEMEKA , CHAN OWEN 
Published: June 2024

We previously demonstrated that poorly controlled type 1 diabetes leads to an increase in extracellular lactate concentrations in the ventromedial hypothalamus (VMH) that contributes to suppressing the counterregulatory hormone responses to hypoglycemia. The mechanisms underlying the increase in VMH lactate in diabetes are not clear. The current study evaluates whether this lactate is derived from the periphery or whether it is generated locally in the brain. To answer this question, we gave conscious, freely moving male Sprague-Dawley rats a 50% glucose bolus (1g/kg) intravenously and measured changes in interstitial glucose and lactate in the VMH using microdialysis while infusing either artificial extracellular fluid (aECF; N=13) or sodium oxamate (OXA; N = 11), a lactate dehydrogenase-A inhibitor, through microinjection needles that targeted the VMH. Our results show that the glucose bolus led to a rapid and dramatic rise in plasma glucose levels, followed by an increase in plasma lactate (300% and 150% change from baseline, respectively). In addition, glucose and lactate in the hypothalamus also increased significantly. However, in animals treated with OXA, the rise in hypothalamic lactate was significantly reduced (P-value = 0.018). In summary, our data suggest that elevated blood glucose in diabetes possibly triggers the local production of lactate in the brain, which may contribute to the development of counterregulatory failure to hypoglycemia.

Disclosure
C. Uzo: None. O. Chan: None.

Funding
University of Utah Diabetes, Metabolism Research Center
1781-LB: Diet-Induced Upregulation of LRG1 Contributes to Renal Lipotoxicity and Damage in Chronic Kidney Disease
Authors: WEI CONG , MORALES DESIRAE , RYU JIYOON , HADLEY JASON , BAI JULI , DUGGIRALA RAVINDRANATH , LYNCH JANE L. , XIAO LI L. , DONG LILY Q. 
Published: June 2024

Obesity and diabetes significantly elevate the risk of chronic kidney disease (CKD). While renal lipotoxicity and damage serve as markers of CKD, the mechanisms driving its progression remain poorly understood. In this study, we measured the protein levels of leucine-rich alpha-2-glycoprotein 1 (LRG1), an adipokine up-regulated in the serum of obese humans and mice, in mouse urine samples. Elevated levels of urine LRG1 were detected in obese mice fed a high-fat diet (HFD) compared to their lean counterparts. Furthermore, whole-body Lrg1 knockout mice exhibited resistance to HFD-induced lipid accumulation and tubular cell damage in the kidney, accompanied by improved ER stress and reduced Chop activity relative to wild-type littermates. Cellular studies revealed that LRG1 treatment alone induced lipid accumulation and fibrogenesis in HK-2 proximal tubule cells by inhibiting fatty acid β-oxidation (FAO) and triggering apoptosis. Moreover, co-treatment of LRG1 with low-dose palmitate acid (50 μM) had a synergistic effect on lipid accumulation in HK-2 cells. In summary, our findings suggest that LRG1 is a urinary protein, and its augmentation in urine may serve as a biomarker for obesity-induced insulin resistance and CKD. Thus, therapeutic targeting of LRG1 could represent an effective strategy to mitigate ectopic fat deposition in the kidney and prevent the exacerbation of obesity-induced CKD.

Disclosure
C. Wei: None. D. Morales: None. J. Ryu: None. J. Hadley: None. J. Bai: None. R. Duggirala: None. J.L. Lynch: Research Support; Beta Bionics, Inc., Novo Nordisk. L.L. Xiao: None. L.Q. Dong: None.

Funding
the Baptist Health Foundation
1783-LB: Acute Hyperglycemia Induces Human Podocyte Apoptosis by Increasing Monocyte Release of TNF-α through ER Stress/ROS Activation of ADAM17/iRhom2 Expression
Authors: MEI ZHANG RONG , OH JISU , KUTZ GRETA A. , DUSSO ADRIANA S. , BERNAL-MIZRACHI CARLOS 
Published: June 2024

Introduction: Targeting glycemic control based on hemoglobin A1c (A1c) reduces but does not abolish the onset and progression of chronic kidney disease (CKD), suggesting factors other than A1c contribute to the residual risk. Acute hyperglycemia is associated with the development of microalbuminuria, but the underlying mechanisms are unknown. This study aimed to identify if acute hyperglycemia is directly toxic to podocytes or by inducing a proinflammatory monocyte phenotype to cause podocyte apoptosis.
Methods: Monocytes, isolated from healthy subjects, were cultured under euglycemic (5mM) or hyperglycemic (16.7 mM) conditions +/- 10 nM GLP-1 for 6h. QPCR measured monocyte expression of iRhom2 and Adam17, genes responsible for TNF-α release. THP-1 cells, differentiated to macrophages with 160 nM PMA for 48h, were exposed to 5 or 16.7 mM D-glucose for 24h +/- 10 nM GLP-1. Human immortalized podocytes were exposed to 5 or 16.7 mM D-glucose conditioned media from monocytes or THP-1 macrophages for 24h. Caspase 3/7 assessed podocyte apoptosis. TNF-α was tested by ELISA.
Results: Acute hyperglycemia had no direct effect on podocyte apoptosis, but induced a proinflammatory monocyte and THP-1 secretome with high TNF-α release causing podocyte apoptosis. In monocytes, acute hyperglycemia for 6h was sufficient to increase oxidative and ER stress and induce ADAM17/iRhom2 expression, facilitating TNF-α release. Monocyte and THP-1 exposure to GLP-1 prevented acute hyperglycemia induction of ADAM17/iRhom2 expression, TNF-α release, and podocyte apoptosis.
Conclusion: These results show a mechanism by which acute hyperglycemia accelerates the early onset of CKD, and highlights the anti-inflammatory role of GLP-1 independent of glycemic control to reduce CKD progression in diabetes.

Disclosure
R. Zhang: None. J. Oh: None. C. Bernal-Mizrachi: None.

Funding
American Heart Association Career Development Award (855967)
1796-LB: Adipocyte-Derived Extracellular Vesicles (AdEVs) Contribute to Insulin Resistance and Atherosclerosis in Obesity
Authors: RIMA XILAL Y. , SHANTARAM DHARTI , LIU JOEY Z. , WRIGHT VALERIE P. , DOON-RALLS JACOB , AMARI ANASTASIIA , JALILVAND ANAHITA D. , NEEDLEMAN BRADLEY J. , NORIA SABRENA , BRETHAUER STACY , PERRY KYLE A. , REATEGUI EDUARDO , HSUEH WILLA 
Published: June 2024

Introduction: Cardiovascular disease is the leading cause of death worldwide. Obesity is a well-known major risk factor for atherosclerosis with 60% of all atherosclerotic burden due to metabolic syndrome, while other factors remain unknown. Adipose tissue (AT) inflammation is likely a contributor. Recently, extracellular vesicles (EVs) have emerged as potential mediators of intercellular and interorgan communication, with EV secretion from adipocytes increasing 4-fold in obese mice. Adipocytes are a primary source of circulating microRNAs (miRNAs), an essential component of AdEV cargo, as well as lipids. Therefore, we hypothesize that AdEVs impact atherosclerosis and may mediate obesity-accelerated vascular damage.
Methods: To test this hypothesis, we retro-orbitally administered 1010 AdEVs harvested from obese and lean mice into 52-week-old atherosclerosis-prone (LDLR-/-) mice, which develop accelerated complex lesions when consuming a western high-fat diet (WHFD).
Results: Despite matched body weights and similar plasma cholesterol levels post-AdEV injection, en-face analysis of the aorta confirmed a significant increase in the atherosclerotic lesions of mice that received AdEVs from obese donors (25 - 30%; p &lt; 0.0001) compared to those that received AdEVs from lean donors (14 - 20%; p &gt; 0.05), which resembled the effect of the saline control. Moreover, mice that were administered AdEVs from obese donors developed worse insulin resistance after AdEV injection than AdEVs from lean donors (p &lt; 0.05). In humans, AdEVs from obese individuals activated monocyte-derived macrophages and initiated a pro-inflammatory cascade, while AdEVs from lean individuals had similar effects to saline. Furthermore, the AdEVs from lean and obese individuals demonstrated differential expression of miRNA and lipid cargo.
Conclusion: These observations highlight the critical role of AdEVs and their cargo in mediating obesity-associated atherosclerosis.

Disclosure
X.Y. Rima: None. D. Shantaram: None. J.Z. Liu: None. V.P. Wright: None. J. Doon-Ralls: None. A. Amari: None. B.J. Needleman: Speaker's Bureau; Metronics, Intuitive Surgical. Advisory Panel; Revmedica. S. Noria: None. S. Brethauer: None. K.A. Perry: Research Support; Ethicon, Inc. E. Reategui: None. W. Hsueh: None.
1799-LB: Identification of Proteomics Signature for Vascular Complications in Type 2 Diabetes
Authors: FRANCIS HABIB , JANUSZEWSKI ANDRZEJ S. , O'ROURKE MATTHEW , HUANG MICHAEL L. , HARDIKAR ANANDWARDHAN A. , JOGLEKAR MUGDHA V. , SULLIVAN DAVID , JENKINS ALICIA , MOLLOY MARK P. , KEECH ANTHONY C. , BEHALF OF THE FIELD STUDY INVESTIGATORS ON 
Published: June 2024

Introduction: Robust predictive measures for Type 2 diabetes (T2D) vascular complications to facilitate early intervention strategies are needed.
Methods: Fasting plasma from 363 Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial participants (mean±SD) age: 61.3±6.4 yrs, 5.6±5.4 yrs T2D, HbA1c: 6.7±1.2% (49.7±13.4 mmol/mol), were collected at baseline and stored (-80°C) until quantitative proteomics analysis of tryptic peptides. Protein signatures associated with future micro- or macrovascular complications (100 and 54 subjects, respectively) were identified using a random forest approach, adjusted for treatment allocation. Exhaustive search using logistic regression was then carried out to optimise models. Pathway analysis was carried out using the NIH functional annotation tool, DAVID Bioinformatics. Resources.
Results: Fifty targets were selected: 14 were associated with microvascular, 13 with macrovascular complications and 23 were common for both. Pathway analysis revealed six main pathways: cholesterol metabolism, platelet activation, complement and coagulation, focal cell adhesion, actin cytoskeleton and hypertrophic cardiomyopathy. In logistic regression, the optimal model for prediction of microvascular complications with overall p&lt;0.0001, AUC=0.74 contained Cadherin-5, Clusterin, Ceruloplasmin, Glutathione peroxidase 3 and Inter-alpha-trypsin inhibitor heavy chain H3. For macrovascular complications the model contained Zinc-alpha-2-glycoprotein and Coagulation factor V (p&lt;0.0001, AUC=0.72). For any micro- or macro-vascular complications, the model contained Cholinesterase, Ceruloplasmin, Mannose-binding protein C and Coagulation factor V (p&lt;0.0001, AUC=0.70).
Conclusion: Proteomic signatures represent a promising first step towards identifying protein signatures associated with T2D complications. Future research will aim at finding therapeutic targets in the metabolic pathways identified by those proteins.

Disclosure
H. Francis: None. A.S. Januszewski: None. A.A. Hardikar: None. M.V. Joglekar: None. D. Sullivan: None. A. Jenkins: Research Support; Abbott, Viatris Inc. Advisory Panel; Abbott. Research Support; Medtronic. Board Member; Insulin for Life. Research Support; Leona M. and Harry B. Helmsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), Jaeb Center for Health Research, National Institutes of Health, National Health and Medical Research Council Australia. M.P. Molloy: None. A.C. Keech: Research Support; Abbott, Amgen Inc., Bayer Inc., Kowa Company, Ltd., Mylan. Speaker's Bureau; Novartis Pharmaceuticals Corporation. Research Support; Novartis Pharmaceuticals Corporation, Sanofi, Viatris Inc.

Funding
National Health and Medical Research Council (GNT1147897)
1806-LB: Improvement in Sensory Function and Achieving Remission of Type 2 Diabetes Mellitus through Digital Twin Technology—A One-Year Intervention Study
Authors: SHAMANNA PARAMESH , DHARMALINGAM MALA , VADAVI ARUN , KESHAVAMURTHY ASHOK , BHONSLEY SUCHITRA , MOHAMED MALUK , SHAH LISA , THAJUDEEN MOHAMED , PANANDIKAR MAHIKA , JOSHI SHASHANK R. 
Published: June 2024

Introduction and Objectives: Digital twin (DT) platform uses Artificial Intelligence (AI) and Internet of Things, to integrate multi-dimensional data for precision nutrition and health recommendations via the mobile app and by coaches. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Status of sensory functions were assessed by monofilament test (MF) and vibration perception (VP) in patients on DT platform.
Methods: We monitored 181 T2DM patients, across 4 centers, for remission of T2DM, with a focus on participants with sensory neuropathy. Statistical analysis, including the Pearson correlation coefficient, explored the link between HbA1c levels and change in sensory functions.
Results: Mean age, duration of diabetes, were 44 years (±8.6) and 3.7 years (±2.7). Mean HbA1c decrease was 3.03 (8.9% to 5.8), indicating significant improvements from baseline to Day 360. 75.69% of the participants (n=137) achieved remission. Sensory function evaluations showed significant improvement: 96.4% (26 of 27) improved touch sensitivity in MF test (p=0.0013), and 63.0% (46 of 73) showed better vibration perception in VP test (p&lt;0.0001). The correlation between remission and sensory test improvements was found to be weak, with MF changes showing a very slight negative correlation (r=-0.0187) and VP changes a slight positive correlation (r=0.0798), indicating that achievement of remission is not a strong predictor of sensory function recovery.
Conclusion: DT has a transformative potential for sensory function recovery among T2DM undergoing remission, evidenced by significant improvements in MF and VP tests. However, the minimal correlation between remission and sensory improvement suggests that the recovery of sensory functions in diabetic neuropathy involves a complex interplay of factors, emphasizing the need for comprehensive management approaches and further research into neuropathic recovery mechanisms.

Disclosure
P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. L. Shah: Employee; Twin Health. M. Panandikar: None. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim.
1807-LB: Comparison between Normal and Diabetes Patients’ Foot Neuro Activity
Authors: KIM WI , PARK MIN S. 
Published: June 2024

One simple diagnostic method to determine foot insensitivity is a nanofilament test or sending a weak electric shock to the patient to detect their response. However, accuracy is an issue due to controlling neurostimulation in the patient. We have developed a device that can detect neuro signals using an electric wavelength between 3-100Hz. We utilize TGAM, which is typically used to detect EEG signals. The device is connected to three different parts located near the Achilles tendon. Synapse signals were collected from 5 normal and diabetic subjects (fasting glucose level over 180mg/dl) by lifting the foot every 3 seconds for 1 minute, using electrodes coated with AgCl. Analog data from the subjects were converted into decimal data and plotted. From the 1-minute response, diabetes patients generated an average of 18.21 signaling spots, whereas normal subjects generated an average of 26.49 signaling spots. Additionally, the total signal created by normal subjects is 633.42% greater than that of diabetes patients. Based on the results, we can conclude that impaired foot movement occurs in diabetes patients due to high glucose levels, which may delay muscle movement by transmitting smaller signal numbers. Furthermore, the signal stimulation itself is also less than normal. Therefore, the progression of diabetic foot may decrease patient movement due to function loss, resulting from reduced signal activity and poor signal transmission.

Disclosure
W. Kim: None. M.S. Park: None.