bluuebunny/crossref_metadata_2025_split huggingface dataset:
1671-P: Safety and Effectiveness of Bariatric and Metabolic Surgery in Older Japanese Patients
Authors: HAYASHI AIKO , TAKEMOTO MINORU , TANAKA TOMOHIRO 
Published: June 2024

Introduction & Objective: According to the current guidelines in Japan, the upper age limit for bariatric and metabolic surgery is 65 y. This study aimed to examine the appropriateness of this upper age limit.
Methods: Using the database maintained by the Japanese Society for Treatment of Obesity, we conducted an analysis of patients in two age groups: those aged &lt;65 y and those aged ≥65 y. Our analysis focused on postoperative weight loss, improvement in comorbidities, and frequency of perioperative complications.
Results: A total of 3649 patients aged &lt;65 y (mean, 43.9 ± 9.5 y) with a preoperative body mass index of 42.5 ± 8.1 kg/m2, while 70 aged ≥65 y (mean, 67.2 ± 3.1 y; maximum,78 y) with a preoperative body mass index of 40.7 ± 6.9 kg/m2. Patients aged ≥65 y had a higher rate of diabetes, dyslipidemia and hypertension. The rates of reoperation, intraoperative complications, and postoperative complications did not differ between the age groups. Both groups achieved significant weight loss postoperatively, and no differences in the improvement of comorbidities were noted.
Conclusion: Metabolic surgery is safe and effective for older patients with clinically severe obesity. Weight loss was less in patients aged ≥65 y, but the percentage of total weight loss did not differ between the groups.

Disclosure
A. Hayashi: None. M. Takemoto: None. T. Tanaka: None.
1690-P: Clinical Outcomes among Nondiabetic Obese Population with Concomitant Metabolic Dysfunction–Associated Steatotic Liver Disease—A Nationwide Study
Authors: KISHORE SINDHU , KHOKHLOV LEONID , MATEO FERNANDO R. , RAJBHANDARI PRANITA , IKPEZE TOCHUKWU , KISHORE MEHWISH , AJENAGHUGHRURE GODBLESS E. , THAPA ANUP 
Published: June 2024

Obesity, a disease increasing cardiometabolic risks and mortality, often accompanies metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is characterized by fat accumulation in the liver without other secondary causes. This study explores clinical outcomes in obese patients without DM co-diagnosed with MASLD. Conducted as an observational study, it utilized data from the National Inpatient Sample from 2017 to 2020 focusing on obese adults over 18 years, with a BMI &gt;30 kg/m^2, and MASLD diagnosis, excluding those under 18 or with DM. Multivariable logistic and Poisson regression analyses determined the clinical outcomes, considering a p-value &lt;0.05 significant. Among 1,140,000 obese adults without DM, 23.4% had MASLD, predominantly white males aged 53-57. The study compared MASLD and non-MASLD groups, revealing higher rates in % in the MASLD group for conditions like anemia (21.8 vs 13.5), pulm HTN (7.6 vs 4), HF (26.6 vs 15.9), Afib (18.7 vs 13.7), PVD (2.4 vs 2.2), ACS (7 vs 4.2), STEMI (1.1 vs 0.6), COPD (19 vs 14.6), CKD (19.5 vs 11), PE (7.2 vs 5.2) and incidences of nicotine (19 vs 15.8) and alcohol use (16 vs 4.3). The former group also had worse primary and secondary outcomes as detailed in Table 1. The findings underscore the importance of obesity detection and management in such populations for better clinical outcomes and prognosis.

Disclosure
S. Kishore: None. L. Khokhlov: None. F.R. Mateo: None. P. Rajbhandari: None. T. Ikpeze: None. M. Kishore: None. G.E. Ajenaghughrure: None. A. Thapa: None.
1704-P: Misperception of One’s Own Obesity Status—Causes and Consequences—Insights from a Large Nationwide Survey
Authors: AGARWAL SANJAY , VISWANATHAN VIJAY , SHARMA JK , SHUNMUGAVELU MINAKSHISUNDARAM , VIRMANI ANIL , MAKKAR BRIJ , KAPOOR NITIN , DESHPANDE NEETA 
Published: June 2024

Introduction & Objective: Correct self-perception of BMI (Body Mass index) status is essential to adopt a healthy lifestyle and experience improved quality of life. The current study evaluates the extent of misperception in the Indian population and its influence on an individual’s perspective on obesity management.
Methods: A large-scale pan-Indian electronically captured survey was conducted using a translated and validated form and disseminated to the public using multiple modalities. The survey responses included demographics, history of comorbidities, perception of BMI, lifestyle practices, and attitude towards obesity management. Chi-square test for proportions was used to compare the responses between groups with correct perception or misperception (overperception - perceived BMI status is higher than actual BMI; undermisperception - perceived BMI status is lower than their actual BMI.
Results: Among the participants (N = 60285), 35.75% had a misperception of their BMI status, higher among men (35%) than women (29.6%). Almost 91% of those with misperception had underperceived their BMI status. The history of comorbid illness was significantly lower with misperception. Among those with a high actual BMI, 73% were unaware of overweight status and 92% of these participants had not taken efforts to lose weight. One-third of the population with misperception did not consider obesity as a disease and were reluctant to receive weight loss information (84.5%).
Conclusion: Misperception of self BMI status is high among the Indian population and could contribute to a setback in their self-awareness of health status (co-morbidities) and reluctance attitude towards obesity management.

Disclosure
S. Agarwal: None. V. Viswanathan: None. J. Sharma: None. M. Shunmugavelu: None. A. Virmani: None. B. Makkar: None. N. Kapoor: None. N. Deshpande: None.
1708-P: Effect of Oral Semaglutide in Glycemic Control and Weight Reduction for People with Type 2 Diabetes Mellitus Having a BMI ≥25 kg/m2—A Six-Month Real-World Study
Authors: KESAVADEV JOTHYDEV , SHANKAR ARUN , SABOO BANSHI D. , ASHIK ASHA , NAINA JUNAID , JOTHYDEV KRISHNADEV , BASANTH ANJANA , RAJ K SOURAV , JOTHYDEV SUNITHA 
Published: June 2024

Overweight and obesity are increasingly recognized as potential targets for early intervention. Unlike injectable treatments, oral formulations are more easily accepted by people with diabetes. In Asian Indians, BMI ≥ 25 kg/m2 is considered obesity. Study participants were de-identified from the electronic medical records of a comprehensive diabetes centre in Kerala, India. The primary outcome variables were assessed at baseline and again at 6 months. Subjects with data spanning from March 2022 to July 2023 and a BMI ≥ 25 kg/m2 were included in the study. Those without follow-up data were excluded. Over six months, oral semaglutide (N=221) significantly reduced HbA1c by 1.38% (95% CI = 0.7 to 2.1, p &lt; 0.001) in T2DM with BMI ≥ 25 kg/m2. A significant reduction was observed with a Mean Absolute Difference (MAD) of 2.2 kg/m2 in BMI (95% CI = 1.1 to 3.3, p &lt; 0.001) and 4.76 kg in weight (95% CI = 2.7 to 6.8, p &lt; 0.001). 27 participants (8%) discontinued due to side effects. (Figure). In this real world study 1 in 3 T2D with obesity achieved a weight loss of 5% and 1 in 2 T2D with obesity achieved reduction in insulin dose. This study provides real-world evidence of sustainable improvements in A1C, weight, and BMI among T2D treated with oral semaglutide.

Disclosure
J. Kesavadev: None. A. Shankar: None. B.D. Saboo: None. A. Ashik: None. J. Naina: None. K. Jothydev: None. A. Basanth: None. S. Raj K: None. S. Jothydev: None.
1711-P: A 3D High-Content Islet Imaging Toolbox
Authors: TITLE ALEXANDRA C. , JAWUREK SAYRO , RUFER CHANTAL , FORSCHLER FELIX , KODIYAN BEN , YESILDAG BURCAK 
Published: June 2024

Previously, we optimized hanging-drop based, scaffold-free and high-throughput reaggregation of primary islet cells to obtain uniform islets that display long-term and robust function. Using our model, we reported type 1 and 2 diabetes relevant stress models that rely on analysis of insulin secretion and insulin and ATP contents. While these biochemical assays effectively assess islet function and viability, they lack the ability to report at a single-cell resolution. Here, we showcase multiple 3D high-content confocal microscopy applications that provide single-cell insights into pancreatic cell function, identity, survival and proliferation. During islet culture, inflammatory stress was induced using proinflammatory cytokines, activated peripheral blood mononuclear cells or islet-specific cytotoxic T lymphocytes. For metabolic stress, glucolipotoxic culture conditions were used. Gene expression was modified via adeno-associated viral transduction during reaggregation. Islet function and viability were analyzed through basal and stimulated insulin secretion, insulin and ATP contents. 3D confocal imaging protocols of key diabetes-relevant targets were established by optimization of islet fixation, permeabilization, blocking, antibody staining, clearing, and high-content imaging followed by high-resolution, multicolor 3D microscopy. In addition, cell tracker dyes were utilized to observe longitudinal real-time islet-immune cell interactions. Images were analyzed with custom CellPathFinder pipelines. These established methods enable quantitative analysis of islet hormone content, amyloid deposition, HLA expression, transduction efficiency, T-cell infiltration, and β- and non-β-cell death, survival, mass and proliferation. In summary, by combining cutting-edge spheroid and 3D high-content imaging technologies, we developed unique tools for quantitative, high-throughput, and automated phenotypic characterization of pancreatic islets in parallel with a variety of functional parameters.

Disclosure
A.C. Title: Other Relationship; Biomea Fusion, Inc., Boehringer-Ingelheim, Novo Nordisk, Merck & Co., Inc. S. Jawurek: Other Relationship; Boehringer-Ingelheim, Merck & Co., Inc., Biomea Fusion, Inc., Novo Nordisk. C. Rufer: Other Relationship; Boehringer-Ingelheim, Novo Nordisk, Merck & Co., Inc., Biomea Fusion, Inc. F. Forschler: Other Relationship; Biomea Fusion, Inc., Boehringer-Ingelheim, Merck & Co., Inc., Novo Nordisk. B. Kodiyan: Other Relationship; Biomea Fusion, Inc., Novo Nordisk, Boehringer-Ingelheim, Merck & Co., Inc. B. Yesildag: Other Relationship; Novo Nordisk, Boehringer-Ingelheim, Biomea Fusion, Inc., Merck & Co., Inc.
1716-P: MiR-106b-5p Protects against Islet ß-Cell Dysfunction and Apoptosis by Modulating the Endoplasmic Reticulum Homeostasis Pathway
Authors: XU WEILONG , YU JIANGYI , ZHOU XIQIAO 
Published: June 2024

Introduction & Objective: Apoptosis plays important roles in the pathophysiology of Type 2 diabetes mellitus (T2DM). Loss of functional β-cell mass is one mechanism by which diabetes can develop. ER stress plays an important role in the progressive reductions in insulin secretion that are associated with β-cell failure and apoptotic β-cell death.We aimed to elucidate the specific molecular mechanisms of β-cell apoptosis by exploring the relationship between miRNA and endoplasmic reticulum homeostasis.
Methods: RNA sequencing was performed to analyse the islets of high-fat diet (HFD)-fed mice and those of normal chow-fed mice (NCD). The function in β-cells of the selected miR-106b-5p was assessed after its overexpression or knockdown in MIN6 cells and primary islet cells, as well as in siRNA-treated mice. Then, RNA pull-down, RNA immunoprecipitation and coimmunoprecipitation were performed to investigate the mechanism of miR-106b-5p regulation of islet function.
Results: MiR-106b-5p was dramatically downregulated in the islets of the obese mice, as well as in the sera of obese donors with type 2 diabetes. Treatment with miR-106b-5p showed a significant decrease in the number of apoptotic β-cells and increased β-cell mass in HFD mice.Furthermore, we demonstrated that miR-106b-5p reshapes endoplasmic reticulum homeostasis and improves β-cells’function by downregulating the expression of GRP78.
Conclusion: Taken together, we clarified that the modulation of the ER homeostasis pathways by miR-106b-5p shifts the translational status from repression to the recovery phase and improves the survival of β-cells by protecting them from apoptosis.

Disclosure
W. Xu: None. J. Yu: None. X. Zhou: None.

Funding
National Natural Science Foundation of China(82174293, 82205025, 82104751)
1732-P: ATP Dynamics in ß-Cell Primary Cilia Depend on Bidirectional Signaling from Ciliary Glycolysis to Mitochondria
Authors: MING HUANG SHIH , FOSTER HANNAH R. , HUGHES JING , MERRINS MATTHEW J. 
Published: June 2024

Primary cilia are specialized antenna-like sensory and signaling organelles present in pancreatic β-cells that play important roles in mediating insulin secretion. However, it remains unclear how cilia are provided with ATP. Here, β-cell deletion of the ATP-generating enzyme pyruvate kinase (PK) was used to investigate autonomous ciliary signaling, while β-cell deletion of mitochondrial Pck2, which supplies PK with mitochondrial PEP, was used to assess extraciliary signaling from the mitochondria. The dynamics of plasma membrane and ciliary signaling were examined in intact islets using live-cell 3D imaging of 5HT6 targeted biosensors. At elevated glucose, plasma membrane ATP/ADP, fructose 1,6-bisphosphate (FBP), and cAMP/PKA exhibit regular oscillatory patterns. Glucose elevation elicited a pronounced drop in plasma membrane ATP/ADP that contrasted with the sustained rise in ATP/ADP observed in cilia, and in many cases antiphasic ATP/ADP oscillations were observed between the two compartments. The cytosol represents a third “compartment” where glucose induced a monotonic rise in ATP/ADP, as shown with untargeted biosensors. In contrast with ATP/ADP, ciliary FBP did not rise in response to glucose, suggesting highly efficient glycolytic signaling within the axoneme. Experiments performed at low glucose with leucine stimulation were used to isolate retrograde PEP signaling from mitochondria to cilia. The leucine-dependent rise in ciliary ATP/ADP observed in control cells was strongly reduced by β-cell deletion of PCK2 or PKm1, with a further reduction in the PKm1/2 double knockout. Taken together, our findings indicate distinct signaling dynamics in the plasma membrane and ciliary domains, and demonstrate the importance of PK and an extraciliary PEP cycle for control of ciliary bioenergetics.

Disclosure
S. Huang: None. H.R. Foster: None. J. Hughes: None. M.J. Merrins: None.

Funding
NIH/NIDDK (R01DK113103 and R01DK127637); United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service (I01BX005113)
1750-P: Rescuing Human Beta-Cell Dysfunction Induced by Proinflammatory Cytokines and Glucotoxicity
Authors: TESI MARTA , SULEIMAN MARA , SEMERARO ROBERTO , DE LUCA CARMELA , BOSI EMANUELE , DEL GUERRA SILVIA , MAGI ALBERTO , CNOP MIRIAM , EIZIRIK DECIO L. , MARSELLI LORELLA , MARCHETTI PIERO 
Published: June 2024

Introduction & Objective: Residual insulin secretion (IS) from surviving beta cells (BC) can be hampered by a stressful T1D islet microenvironment (e.g. cytokines - Cyt, increased glucose - G). We evaluated the effects of Cyt and Cyt+G on isolated human islet (HI) IS, assessed if BC dysfunction is reversible, and explored the associated molecular mechanisms.
Methods: HI from five nondiabetic organ donors (age, 78±15 yrs; BMI, 24.4±3.8 kg/m2) were exposed to Cyt (50 U/ml IL-1β + 1000 U/ml IFN-γ) at 5.5 or 11.1 mM G for 24h, followed by 72h culture in normal medium (wash-out, WO). IS at 3.3 and 16.7 mM G was assessed, and HI transcriptome evaluated by RNA sequencing.
Results: Cyt increased IS by 2-fold at 3.3 and 16.7 mM G, with an insulin stimulation index (ISI) of 5.3±2.3 (similar to that of control HI: 5.0±2.7). After WO, no change in IS was observed. Combined Cyt+G decreased ISI by &gt; 50% (2.1±0.6); it improved after WO (4.0±1.1), due to better IS at 16.7 mM glucose. Transcriptome of Cyt+G washed-out vs exposed HI showed 3,137 differentially expressed genes (padj&lt;0.01, log2FC≥1, ≤-1, 1,443 up- and 1,694 down-regulated). By GSEA, 10 pathways were positively enriched (including Glycolysis/Gluconeogenesis, AMPK signaling and Metabolic pathways) and 65 negatively enriched (including Cytokine-cytokine receptor interaction, signaling by IL-17, TNF, JAK-STAT and NF-kB, Spliceosome, Protein processing in ER).
Conclusion: Short-term exposure to Cyt increased HI IS, which persisted after WO. Combined Cyt+G impaired BC function, which recovered after WO. The improvement was associated with transcriptomic changes in metabolic processes, inflammatory pathways and the innate immune system. These data suggest that human BC function can be rescued in a T1D-like environment by alleviating the insult and/or targeting underlying molecular mechanisms.

Disclosure
M. Tesi: None. M. Suleiman: None. R. Semeraro: None. C. De Luca: None. E. Bosi: None. S. Del Guerra: None. A. Magi: None. M. Cnop: None. D.L. Eizirik: None. L. Marselli: None. P. Marchetti: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk.

Funding
Innovative Medicines Initiative 2 (115,797 and 945,268), European Commission and Italian Ministry of University and Research within the PNRR Project (M4C2-I1.3 PE_00000019 HEAL ITALIA)
1786-LB: Twenty-Four-Hour Ambulatory Blood Pressure and Vascular Complications in Type 1 Diabetes Subjects—Systematic Review and Meta-analysis of Prospective Studies
Authors: HOFFMEISTER MARIANA C. , FRIEDRICH EDUARDO P. , LOVISON VINÍCIUS H. , RODRIGUES TICIANA 
Published: June 2024

Introduction & Objective: Office blood pressure (BP) measures may not identify early changes in BP that may indicate risk of development or progression of complications in diabetic individuals. The 24hour ambulatory blood pressure (ABP) offers more BP measures, including sleeping time. Our objective was to evaluate the ABP as a predictor of vascular outcomes in office normotensive patients with type 1 diabetes subjects (T1D) over time.
Methods: Systematic review with meta-analysis at Embase, PubMed/Medline and Web of Science database including cohort studies in normotensive T1D patients underwent to ABP at baseline and subsequent evaluation of vascular complications during follow-up. Measurements of difference (mmHg) were obtained using a random effect model for each variable of ABP (systolic and diastolic BP - day, night and 24h).
Results: Only 7 out of 364 articles were included, 635 participants were evaluated, age 25.8±6.2 years, 57% male, diabetes duration 11.8±5.3 years, HbA1c 8.5%±1.6, over 4.2 years. Lower nighttime systolic BP -4.37 mmHg (95%CI -6.96;-1.79, p0.0009, I²30%) and nighttime diastolic BP-3.97 mmHg (95%CI -5.85;-2.10, p &lt;0.0001, I²0%,) at baseline were associated to renal protection. Lower nighttime diastolic BP -3.62 mmHg (95%CI -7.18;-0.06, p0.042, I²0%), daytime diastolic BP -2.69 mmHg (95%CI -4.84;-0.55, p0.0138, I²0%) and 24h diastolic BP -3.65 mmHg (95%CI -6.56;-0.75, p0.037, I²0%) were associated with better ocular outcomes. Macrovascular and neuropathy outcomes were not found.
Conclusion: In T1D patients lower nocturnal BP values ​​were associated with better microvascular outcomes. The office BP would not be able to identify these cases. ABP should be included in the care of patients with diabetes.

Disclosure
M.C. Hoffmeister: None. E.P. Friedrich: None. T. Rodrigues: None.

Funding
CAPES and CNPq
18-OR: The Effect of a Dietary Intervention on Insulin Sensitivity in Type 1 Diabetes and the Role of Dietary Advanced Glycation End-Products—A 12-Week Randomized Clinical Trial
Authors: KAHLEOVA HANA , ZNAYENKO-MILLER TATIANA , BARNARD NEAL 
Published: June 2024

Background: This study compared the effect of a low-fat vegan diet with a portion-controlled diet on insulin sensitivity in people with type 1 diabetes and explored the role of dietary advanced glycation end-products (AGEs).
Methods: Fifty-eight adults with type 1 diabetes were randomly assigned to a vegan (n=29), or a portion-controlled group (n=29) for 12 weeks. Insulin sensitivity was assessed, using the carbohydrate to insulin ratio. The content of all meals was recorded using the Cronometer mobile application. Total insulin dose was calculated as a sum of basal and bolus insulin units injected per day.
Results: Insulin sensitivity increased in the vegan group by 6.6 (p=0.002), compared with no significant change in the portion-controlled group (-1.6; p=0.26; treatment effect +8.2 [95% CI, +3.6 to +12.8]; p=0.001). Total dietary AGEs decreased in the vegan group by 7,123 ku/day (95% CI, -9,493 to -4,756; p&lt;0.001), compared with no significant change in the portion-controlled group (treatment effect -5,076 ku/day [95% CI, -8,605 to -1,548]; p=0.006). Change in total dietary AGEs correlated negatively with changes in insulin sensitivity (r=-0.48; p=0.004) and remained significant after adjustment for changes in BMI (r=-0.35; p=0.048). A 1-unit increase in insulin sensitivity was associated with a reduction in dietary AGEs by 2,090 ku/day.
Conclusions and Interpretation: This study suggests that a low-fat vegan diet improves insulin sensitivity in people with type 1 diabetes compared with a portion-controlled diet, and the reduction in dietary AGEs seems to be one of the mediating mechanisms. Larger trials are needed to confirm these findings.

Disclosure
H. Kahleova: None. T. Znayenko-Miller: None. N. Barnard: None.

Funding
Institute for Technology in HealthcarePhysicians Committee for Responsible Medicine
1801-LB: Discovering Novel Cathepsin L Inhibitors Using Artificial Intelligence for Diabetic Nephropathy
Authors: LI QI 
Published: June 2024

Introduction & Objective: Cathepsin L (CTSL) has been demonstrated to play a significant role in the pathogenesis and progression of Diabetic Nephropathy (DN). However, there are currently no CTSL inhibitors available for clinical use. This study utilizes artificial intelligence models to discovering novel CTSL inhibitors and explores their application in DN.
Methods: We developed a neural network model to predict the inhibitory potential of molecules against CTSL activity. This model was then applied to a library of biologically active compounds and conducted activity assays on the top-ranked molecules. We then co-treated HK2 cells with selected CTSL inhibitors and free fatty acids to observe changes in epithelial-mesenchymal transition and inflammation levels between the medicated and normal groups.
Results: We identified five small molecules significantly reduced the activity of CTSL in a live-cell system at the nanomolar level. Notably,10μM of S7391 significantly reduced CTSL expression levels in HK2 cells, while restoring the levels of epithelial-mesenchymal transition-related genes and inflammatory factors to those of the control group.
Conclusion: We successfully developed a deep learning model capable of predicting whether small molecule compounds can inhibit the enzymatic activity of CTSL and identified five small molecules that can inhibit CTSL's enzymatic activity at the nanomolar level. Among these, S7391 was able to reverse renal tubular damage induced by free fatty acids, indicating its potential as a therapeutic drug for diabetic kidney disease through the inhibition of CTSL activity.

Disclosure
Q. Li: None.

Funding
National Natural Science Foundation of China (81930019)