bluuebunny/crossref_metadata_2025_split huggingface dataset:
1679-P: L-arginine Ameliorates Polycystic Ovary Syndrome and Attenuates Intestinal Oxidative Stress by Regulating Gut Microbiota
Authors: DILIMULATI DILIQINGNA , CAI MEILI , ZHANG YUQIN , QU SHEN , ZHANG MANNA 
Published: June 2023

More than half of Polycystic ovary syndrome (PCOS) women are overweight or obese, and weight gain amplifies and worsens the symptoms of PCOS. Hence, it is essential to further understand and treat PCOS women with obesity. Therefore, this study tried to use a multi-omics approach that integrates the gut microbiome, serum metabolomics, serum transcriptomics, and clinical indicators to distinguish obese PCOS from obese non-PCOS women. The stool and blood samples from 33 obese PCOS patients and 30 obese control women were collected. The sequencing results suggested there were significant differences in gut microbiome and metabolites between obese PCOS women and obese women. Of which, the level of L-arginine (Arg) in obese PCOS patients was significantly lower than that in the control group and associated with gut microbiota alterations. Further correlation analysis between metabolite and clinical phenotype showed that Arg was significantly correlated with the clinical phenotype of obese PCOS patients. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) with a high-fat diet (HFD) to induce obese PCOS mice models for 3 weeks. PCOS mice were randomly divided into four groups: Arg group, Arg + antibiotic cocktail (ABX) group, PCOS group, and PCOS + ABX group. After 3 weeks of Arg supplementation, the estrous cycle, ovarian morphology, intestinal oxidative stress and intestinal barrier integrity were improved in Arg group PCOS mice, while testosterone levels and insulin resistance levels were decreased. However, these improvements were not observed in the Arg plus ABX group, suggesting that ABX-mediated depletion of the gut microbiome would eliminate these improvements. Then the 16s rRNA sequencing was performed to determine the gut microbiota of the four groups. The results showed that Arg can ameliorate reproductive characteristics of PCOS and attenuate intestinal oxidative stress by regulating gut microbiota.

Disclosure
D.Dilimulati: None. M.Cai: None. Y.Zhang: None. S.Qu: None. M.Zhang: None.
1689-P: Macrophage SUCLA2-Coupled Glutamine Metabolism Drives Obesity
Authors: JIANG HAOWEN 
Published: June 2023

Activation and infiltration of macrophages in adipose tissue are closely linked to obesity and are implicated in the pathogenesis of metabolic diseases. Glutamine is an essential energy resource that supports the inflammatory activation of macrophages, however, the underlying mechanism remains unknown. We found that AMP-activated protein kinase (AMPK) was the key regulator for mitochondrial glutamine metabolism. Once inflammatory activation of macrophages, increased ATP production from glutaminolysis inhibited the activity of AMPK, then removed its inhibitory effect of glutamine metabolism, resulting in the succinate accumulation derived IL-1β production and secretion. Mechanically, macrophage AMPK phosphorylated at Ser60 of succinyl-CoA synthetase β subunit (SUCLA2) that was responsible for catalyzing the succinate production, decreases its activity resulting in the reduction of the succinate accumulation derived IL-1β production and secretion correspondingly. Moreover, myeloid cell-specific knockout of the α subunit of AMPK exacerbated obesity and insulin resistance through IL-1β production and secretion in macrophages. Both the obstruction of the IL-1β signaling pathway by the neutralizing antibody and the decreasing of IL-1β production and secretion by myeloid cell-specific knockout of IL-1β could repair insulin resistance and obesity derived by AMPK deficiency in macrophages. Our study revealed that AMPK-mediated SUCLA2 phosphorylation drove the mitochondrial glutamine metabolism and the IL-1β production and secretion in macrophages, and targeting macrophage AMPK-SUCLA2 pathway might be a potential strategy for obesity and insulin resistance therapy.

Disclosure
H.Jiang: None.
1694-P: Impact of Bariatric Surgery on Increased Circulating Levels of Several Biomarkers for Neurodegenerative Diseases in Obese Chinese
Authors: YANG RANYAO , LI HUIXIN , YANG WAH , WU QIUPING , JIN LEIGANG , SONG ERFEI , WANG CUNCHUAN , XU AIMIN 
Published: June 2023

Background: Increasing studies have shown a strong association of obesity with neurodegenerative disorders. However, there is scarce evidence for the direct link between obesity and neurodegeneration. In addition, although bariatric surgery is well-known to be an effective therapy for obesity-related metabolic dysfunctions, its impact on cognitive function remains uncertain. This study aims to address these questions by monitoring several well-established circulating biomarkers for neurodegeneration in morbidly obese subjects receiving bariatric surgery.
Methods: The single molecule array, an ultra-sensitive enzyme-linked immunosorbent assay technique, was used for measurement of plasma levels of p-tau 181, tau, Aβ42 and Aβ40 in 36 morbidly obese individuals (BMI=39.46±7.87) before and after bariatric surgery for 12 months and 55 lean subjects (BMI=21.79±2.84).
Results: Plasma levels of p-tau 181, tau, Aβ42 and Aβ40 in obese individuals, were significantly elevated compared to lean individuals, and positively correlated with several indices of obesity, including body weight, BMI and waist circumference. In obese subjects who received bariatric surgery, significant improvements on many metabolic parameters were observed, such as BMI, HOMA-IR and triglyceride. However, circulating p-tau 181 levels in obese individuals kept unchanged before and after treatment, while tau, Aβ42 and Aβ40 levels increased from 4.34±0.74 to 6.06±0.38 pg/ml, 4.37±0.51 to 8.47±0.41 pg/ml, and 98.89±11.53 to 174.14±8.99 pg/ml, respectively.
Conclusions: Circulating levels of several neurodegenerative biomarkers are elevated in obesity but such changes cannot be reversed by bariatric surgery. These findings implicate the adverse effects of obesity at the early stage of life on neurodegeneration may be last-lasting and hardly repairable, highlighting the importance of maintaining a healthy weight in prevention of neurodegenerative diseases.

Disclosure
R.Yang: None. H.Li: None. W.Yang: None. Q.Wu: None. L.Jin: None. E.Song: None. C.Wang: None. A.Xu: None.

Funding
Hong Kong Research Grants Council (AoE/M/707-18)
1697-P: Waist Circumference, Hippocampal Volume, and Cognitive Impairment—A Mendelian Randomization
Authors: ZHANG JINYAN , LUAN SISI , ZHOU JIANBO 
Published: June 2023

The Relationship Between Central Obesity, Cognitive Function, Structural Brain Outcomes: A Mendelian Randomization Study
We investigated the relationship between central obesity and cognitive function, brain structure using a Mendelian randomisation (MR). Our exposures were genetic instruments for waist circumstance (WC, 65 variants) and our outcomes were cognitive performance and hippocampal volumes. We used conventional inverse-variance weighted (IVW) MR as the primary analysis method, alongside MR sensitivity analyses. Using IVW, genetic liability to WC was associated with cognitive performance (exponentiated ß=-0.16, 95%CI=0.07; 0.24), volume of left hippocampus (expß=-0.15, 95%CI=0.02; 0.27) and volume of right hippocampus (c=-0.14, 95%CI=0.01; 0.27). Furthermore, we found two variants in hippocampal volume that were also associated with WC, these two variants were associated with cognitive function (expß = 0.006, 95%CI=0.003; 0.009). Overall, we observed evidence of causal association between genetic instruments for WC and cognitive performance, and volume of hippocampus may be a mediator linking WC with cognitive function.
Table 1 MR estimates of the effect of WC on cognitive function and left or right hippocampus volume.

Disclosure
J.Zhang: None. S.Luan: None. J.Zhou: None.
17-OR: ADA Presidents' Select Abstract: CGM Initiation within Six Months of T1D Diagnosis Associated with Lower HbA1c at 3 Years
Authors: MANN ELIZABETH A. , ROMPICHERLA SAKETH , NOOR NUDRAT , MIYAZAKI BRIAN , GOLDEN LAUREN , SARHIS JENNIFER , AKTURK HALIS K. , LEE JOYCE M. , DESALVO DANIEL , GOMEZ PATRICIA , EBEKOZIEN OSAGIE , PRAHALAD PRIYA 
Published: June 2023

Background: Early initiation of CGM after T1D diagnosis has been associated with lower HbA1c in the years following diagnosis in single-institution studies. This multi-institution study evaluated the association between the timing of CGM initiation and HbA1c at 3 years post-diagnosis.
Methods: Data were obtained from the T1D Exchange QI Collaborative, representing 52 centers across the US. Of the 33,942 youth ≤18 years with T1D &gt;12 months in the Collaborative data set, those who started CGM within 12 months of diagnosis were included. LOESS plots evaluated the relationship between timing of CGM initiation and HbA1c.
Results: Of the 5,339 youth included in this analysis, median age was 9 (IQR 6) and 26% had public health insurance. Initiation of CGM occurred within 3-months of diagnosis for 43%, between 3-6 months for 27%, and 6-12 months for 30%. There was no significant difference in CGM initiation based on insurance or the social construct of self-identified race and ethnicity, used as an indicator of systemic racism. Median HbA1c at 3 years was lower for those who initiated CGM within 3 months and between 3-6 months of diagnosis compared to those starting CGM at 6-12 months (7.3 ± 1.7 and 7.5 ± 1.7 vs. 7.9 ± 1.7; Figure 1).
Conclusion: In summary, early initiation of CGM within the first 6 months of diagnosis is related to improved A1c outcomes at 3 years post-diagnosis.

Disclosure
E.A.Mann: None. P.Gomez: None. O.Ebekozien: Advisory Panel; Medtronic, Research Support; Eli Lilly and Company, Dexcom, Inc. P.Prahalad: None. S.Rompicherla: None. N.Noor: None. B.Miyazaki: None. L.Golden: None. J.Sarhis: None. H.K.Akturk: Advisory Panel; Senseonics, MannKind Corporation, Research Support; Medtronic, Tandem Diabetes Care, Inc., Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company, IM Therapeutics. J.M.Lee: Advisory Panel; GoodRx, Consultant; Tandem Diabetes Care, Inc. D.Desalvo: Consultant; Dexcom, Inc., Research Support; Insulet Corporation.
170-LB: Do Telemedicine vs. In-Person Outpatient Type 1 Diabetes Visits Immediately Improve Glycemic Control?
Authors: FERBER CHRISTOPHER J. , WILHALME HOLLY , MITTELMAN STEVE , MOIN TANNAZ , HICKS REBECCA A. 
Published: June 2023

Background: Children with type 1 diabetes (T1D) require frequent outpatient evaluation to assess glucose trends, modify insulin doses, and stay up to date with screening. Continuous glucose monitoring (CGM) has become more prevalent in recent years and provides a detailed glycemic control assessment. Telemedicine is increasingly utilized in lieu of in-person visits, especially since the onset of the COVID-19 pandemic.
Objective: To assess a difference in CGM profile parameters in the periods immediately before and after T1D follow-up visits and determine whether being seen by telemedicine versus in-person impacts this difference.
Methods: A dual center retrospective chart review was conducted including outpatient T1D follow up visits for patients aged 5-21 years old utilizing Dexcom CGM during the 2021 calendar year. CGM profile parameters assessed were Time in Range (TIR) and Glucose Management Indicator (GMI) during the period 4-weeks leading up to each outpatient visit, compared to the 2-week and 4-week period immediately following.
Results: A total of 269 outpatient visits (41.2% telemedicine) among 135 patients were included from both study sites. Mean TIR increased by 1.63 and 1.35% during the 2-week and 4-week period after each visit, respectively (p = 0.003, 0.013). Mean GMI also improved, decreasing by 0.07% and 0.06% during the 2-week and 4-week period after each visit, respectively (p = 0.003, 0.021). These changes in TIR and GMI were not statistically different between telemedicine versus in-person visits (p = 0.40, 0.29).
Conclusions: This study detected a small, but statistically significant improvement in CGM profile parameters immediately after outpatient visits. Telemedicine versus in-person visits were comparable. These findings suggest that multiple visits over time are needed to obtain a sustainable, clinically relevant change in glycemic control, and telemedicine can be utilized just as effectively as traditional visits to achieve this goal.

Disclosure
C. J. Ferber: None. H. Wilhalme: None. S. Mittelman: None. T. Moin: None. R. A. Hicks: None.
170-OR: Hyperglycemia in Patients without Diabetes in the Emergency Department and Subsequent Cascade of Care
Authors: MASHOUF KIMIA , JOHNSON ARIANNE , WILSON MARK 
Published: June 2023

Introduction: Hyperglycemia in patients without a history of diabetes (DM) is common in the Emergency Department (ED). Data describing how this is routinely managed is lacking. In this study, we report how often patients in the ED without a history of diabetes and hyperglycemia (blood glucose (BG) &gt; 200 mg/dL) receive a HbA1c and diabetes education (DE).
Methods: This retrospective study evaluates patients in our ED with a random BG ≥ 200 mg/dL and no prior history of DM based on medical record review. In total, 110 charts were analyzed. These patients were divided into two groups: admitted for inpatient treatment (AD) and discharged from the ED (DCED). 90-day endpoints included: HbA1c performed and completion of DE. We also compared the frequency of diabetes diagnosis in these populations.
Results: Of the 110 patients studied, 62 (56%) were AD and 48 (44%) were DCED. Within 90 days from the ED visit, 40 (65%) of AD had an HbA1C performed compared to 18 (38%) of DCED. Of AD patients, 25 (63%) were diagnosed with DM based on HbA1c ≥ 6.5%, compared to 13 (72%) of those DCED. Of patients with a new diagnosis of DM, 22 (88%) of AD received DE, while only 4 (31%) of DCED patients received DE.
Conclusion: We have determined that patients with hyperglycemia without a history of DM in our ED are inadequately screened for DM. 53% of this population received HbA1c evaluations within 90 days. Of patients who had a HbA1c performed, 66% were diagnosed with diabetes. AD patients were approximately twice as likely as those DCED to have a HbA1c performed. AD patients with a diagnosis of diabetes were three times as likely to have met with a diabetes educator relative to those DCED. Hyperglycemia in our ED is an opportunity to diagnose DM that is currently underutilized.

Disclosure
K.Mashouf: None. A.Johnson: None. M.Wilson: Stock/Shareholder; Novo Nordisk, Dexcom, Inc.
1705-P: Expression of Selected MicroRNAs in Adipose Tissue-Derived Mesenchymal Stem Cells and Metabolic Syndrome
Authors: WYSTRYCHOWSKI GRZEGORZ , SIMKA-LAMPA KLAUDIA , WITKOWSKA AGNIESZKA , SOBECKO EWELINA , SKUBIS-SIKORA ALEKSANDRA , SIKORA BARTOSZ , WOJTYNA EWA , GWIZDEK KATARZYNA , GOLDA AGNIESZKA , WRÓBEL MARTA , KRUSZNIEWSKA-RAJS CELINA , GOLA JOANNA 
Published: June 2023

Adipose tissue mesenchymal stem cells (AdMSC) secrete microRNAs (miR). Although miR are involved in pathogenesis of metabolic syndrome, the role of those secreted by AdMSC remains elusive.
We aimed to assess expression of selected miR by AdMSC in relation to basic metabolism parameters in nondiabetic adults.
For this preliminary study 10 obese, 8 overweight and 5 normal weight subjects with no inflammatory or cancerous disease were enrolled, including 19 female and 6 prediabetic ones. AdMSC were harvested from abdominal subcutaneous fat and cultured in standard conditions. Expressions of four miR reported in metabolic disturbances were estimated with RT-qPCR. Total and visceral fat were assessed with bioimpedance.
Expression of miR-21, miR-122, or miR-192 did not correlate with any clinical parameter. On the other hand, expression of miR-155 [2-ΔCt] was lowest in obese subjects (3.69±2.67 vs. 7.07±4.42 in overweight and 10.25±7.05 ×10-3 in normal weight ones, P =0.04, K-W ANOVA). It correlated inversely with BMI, total fat mass, visceral adiposity, and serum CRP, whereas positively (marginally significantly) with serum HDL-cholesterol (table 1).

Expression of miR-155 in AdMSC appears blunted in visceral obesity, which correlates with HDL-dyslipidemia and microinflammation. This calls for further study of AdMSC miR secretome in the pathogenesis of metabolic syndrome with focus on miR-155.

Disclosure
G. Wystrychowski: Other Relationship; Polfa Tarchomin. K. Simka-Lampa: None. A. Witkowska: None. E. Sobecko: None. A. Skubis-Sikora: None. B. Sikora: None. E. Wojtyna: None. K. Gwizdek: None. A. Golda: Other Relationship; Servier Laboratories. M. Wróbel: Other Relationship; Novo Nordisk, Lilly, Boehringer Ingelheim Inc. C. Kruszniewska-Rajs: None. J. Gola: None.

Funding
Medical University of Silesia, Katowice, Poland
1706-P: Obesity-Related Cancer Increased Sharply in Young Adults among Chinese Population from 2007 to 2021
Authors: YANG JIN-KUI , LIU CHANG , YUAN YINGCHAO 
Published: June 2023

Objective: The burden of obesity-related cancer has rarely been investigated. This study aims to investigate the trends of incidence of obesity-related cancer in a Chinese population.
Method: During 2007-2021, a population-based registry of cancer covering 14.14 million people was performed in 207 medical sites by the Beijing Municipal Health Commission Information Center. We compared the trends of incidence of obesity-related cancers and non-obesity-related cancer.
Results: Overall, there were 651,482 incident cancer patients in this population from 2007 to 2021. Of these patients, 48.49% were obesity-related cancers. For all obesity-related cancers combined, the age-standardized incidence rates (ASR) showed a significant upward trend (3.6% per year, P&lt; 0.001). Conversely, for non-obesity-related cancers, the ASR was stable during this period (Fig.1 Age-specific differences of all cancers: A,B: annual changes; C,D: incidence rate ratio; E,F: incidence). We predict that the ASR for obesity-related cancers will increase 2.62-fold in 2035 compared to 2021, and will increase mainly in people younger than 50 and decrease in those over 75 years.
Conclusion: Obesity-related cancer incidence significantly increased from 2007 to 2021. While most cases were diagnosed in old people, the obesity-related incidence increased sharply in young adults. These will increase the burden of cancer in the future.

Disclosure
J.Yang: None. C.Liu: None. Y.Yuan: None.

Funding
National Natural Science Foundation of China (81930019)
1708-P: Comparing 9- vs. 12-Month Implantation in the Worldwide EndoBarrier (EB) Registry
Authors: RYDER ROBERT E. , YADAGIRI MAHENDER , MUNRO LYNNE , FRYDENBERG HARRY , FISHMAN SIGAL , BYRNE JAMES P. , TEARE JULIAN P. , DE JONGE CHARLOTTE , WILLEM GREVE JAN , MCMASTER JESSICA J. , CHISHOLM JACOB , KOW LILIAN , MASON JOHN C. , COHEN RICARDO V. , SEN GUPTA PIYA 
Published: June 2023

Uncertainty exists re risk: benefit of proximal intestinal exclusion with EB, a novel endoscopic duodenal jejunal liner device for obesity, both with and without diabetes. In view of this, during 2017, an independent, secure, on line registry was established under the auspices of the Association of British Clinical Diabetologists, for the collection of safety and efficacy data worldwide. As of December 2022, data had been entered on 1022 patients, of whom 195 (age 51.6±10.3 years, 53% male, 81% white ethnicity, BMI 39.9±6.9kg/m2) had both 9- and 12-month data entered. EB had considerable impact on weight and HbA1c (Table). There was no difference between the mean±SD reduction in HbA1c or weight at 9- vs 12-months (HbA1c: 1.39±1.67% vs 1.38±1.66% (p=0.98); weight: 11.7±8.3kg vs 12.0±8.3kg (p=0.44). The higher the HbA1c the greater the fall but again no difference between 9- and 12-months (Table). In the full registry, 43/1022 (4.2%) experienced serious adverse events (SAE). 15/43 (34.9%) SAE would have been avoided by removal at 9-months (9 liver abscess, 4 GI bleed, one cholecystitis). It was particularly noteworthy that 9/13 (69.2%) liver abscess SAEs would have been avoided by removal at 9-months. This international data from the EB registry suggests that the benefits of EB are achieved in 9-months and a reduction in the recommended implantation period from 12- to 9-months would reduce SAEs, especially the liver abscess SAE.

Disclosure
R.E.Ryder: Other Relationship; Novo Nordisk, Speaker's Bureau; GI Dynamics, BioQuest. J.J.Mcmaster: None. J.Chisholm: None. L.Kow: None. J.C.Mason: None. R.V.Cohen: Advisory Panel; GI Dynamics, Research Support; Medtronic, Johnson & Johnson Medical Devices Companies. P.Sen gupta: Other Relationship; Novo Nordisk. M.Yadagiri: None. L.Munro: None. H.Frydenberg: None. S.Fishman: None. J.P.Byrne: Advisory Panel; Oxford Medical Products, Join Embla, Stock/Shareholder; Join Embla. J.P.Teare: None. C.De jonge: None. J.Greve: Advisory Panel; GI Dynamics.

Funding
Association of British Clinical Diabetologists
1710-P: Uncovering Germline Copy Number Deletions Associated with Obesity and Lipid Traits by UK10K Whole-Genome Analysis
Authors: HUN OHN JUNG 
Published: June 2023

We investigated the association of common high-confidence germline copy number deletions (CNDs) with metabolic traits by analyzing UK10K consortium data, where whole genome sequencing (WGS) was performed on 3,781 participants in two UK cohorts, TwinsUK (n=1,854) and ALSPAC (n=1,927). TwinsUK enrolled adult (mean age=59) females and ALSPAC followed children from birth to adolescence. BMI, total fat mass (TFM), truncal fat mass (TrFM), HDL, LDL, VLDL, glucose and insulin were measured. After excluding rare CNDs (MAF&lt;5%) 1,222 (TwinsUK) and 1,211 (ALSPAC) common CNDs remained for association analyses. The genome-wide significance threshold was set at 4.09×10-5(TwinsUK) and 4.13×10-5(ALSPAC) after Bonferroni correction at level α=0.05 and five CNDs achieved genome-wide significance. At ALSPAC, a common (MAF=0.11) 7kb deletion on chromosome 11 (55031591-55038554;BMI at 15yrs,β=1.49, P=2.75×10-6;TFM at 9yrs,β=0.96, P=2.63×10-6;TrFM at 9yrs,β=0.45, P=2.15×10-6) with loss of exons from 2 to 6 in TRIM48 (Tripartite Motif Containing 48), E3 ubiquitin-protein ligase, was associated with childhood obesity. Two other loci at chromosome 8 (intergenic, 24972435-24990944;BMI,β=0.93, P=1.78×10-5;TFM,β=1.39, P=3.58×10-6; TrFM,β=0.64, P=4.56×10-6) and 11 (intron 2 deletion of lincRNA, LOC44040, 49759283-49760872;BMI,β=1.03, P=1.72×10-6; TFM,β=1.29, P=1.31×10-5; TrFM,β=0.60, P=1.66×10-5) were associated with childhood obesity. At TwinsUK, a common (MAF=0.29) 823bp deletion in intron 3 of lncRNA, LINC01923, on chromosome 18 (74347187-74348010,β=-0.22, P=4.15×10-7) was associated with low HDL. The genome-wide significant association of 3kb deletion in GUSBP1 (GUSB Pseudogene 1) enhancer on chromosome 5 (21611834-21614796) with childhood obesity (TFM at 9yrs,β=1.26, P=2.52×10-5) in ALSPAC was replicated in adult females of TwinsUK (TFM, P=3.79×10-2). Studies are warranted that investigate germline CNDs associated with metabolic traits.

Disclosure
J.Ohn: None.

Funding
Seoul National University Bundang Hospital Research Fund (18-2018-0006)