bluuebunny/crossref_metadata_2025_split huggingface dataset:
1893-LB: Effects of High Fibers and Probiotics Supplements Diet and Lifestyle Intervention in Type 2 Diabetes or Prediabetes—A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
Authors: WANG XIANGHONG , WEN JINGHUI , PANG LICHUN , LI PENG , GENG XIAOJING , ZOU LINGLING , YANG ZHE , LI XIAOBING , LU HONGYUN 
Published: June 2024

High-fiber diets and lifestyle interventions have been shown to be the most effective ways to treat metabolic diseases such as obesity and diabetes, but which treatment is more effective and how effective the combination of these two interventions remain unclear. This study evaluated the clinical efficacy of a high-fiber and probiotic supplement diet (HFPD) combined with a lifestyle intervention (LSII) in overweight or obese patients with type 2 diabetes mellitus (T2DM) or prediabetes, and analyzed their impact on patients' gut microbiota and metabolomics. A randomized, double-blind, placebo-controlled trial was conducted in obese or overweight patients with T2DM or prediabetes (ChiCTR1800016411). 110 eligible participants were enrolled, randomly assigned to 4 groups (1:1:1:1) as following, HFPD add LSII group (HL), HFPD add non-LSII group (HNL), placebo add LSII group (PL), and placebo add non-LSII group (PNL) to complete the this 12-weeks treatment. Our results showed that HbA1c in the HL group decreased significantly compared with that in the PL group (-0.7±0.7% vs -0.4±0.9%, P=0.0166). The Hip circumference in PL group decreased more significantly than that in PNL group (-2.2±3.1 cm vs -0.2±3.6 cm, P=0.0244). In addition, compared with PNL group, HL group was significantly better in reducing body weight (-4.2±3.7kg vs -1.7±3.6 kg, p=0.0203), body mass index (-1.6±1.5kg/m2 vs -0.7±1.3kg/m2, p=0.0249), hip circumference (-3.3cm±4.1cm vs -0.2±3.6cm, p=0.0070), HbA1c (-0.7±0.7% vs -0.2±0.7%, p=0.0147) and HOMA-IS (0.18±0.36 vs -0.01±0.20, p=0.0263). Combining further 16S rRNA sequencing and untargeted metabolomics studies suggests that HFPD and LSII both contribute to reducing weight and BMI in obese or overweight T2DM patients, and their combined use is particularly significant in improving metabolic parameters. This may be related to the improvement of the patients' gut environment.

Disclosure
X. Wang: None. J. Wen: None. L. Pang: None. P. Li: None. X. Geng: None. L. Zou: None. Z. Yang: None. X. Li: None. H. Lu: None.
1906-LB: Identification of Missed Mealtime Insulin in Type 1 Diabetes Using Connected Insulin Pens
Authors: WOLPERT HOWARD , XUE JIE , CHEN CHAO , DAVIDSON MICHAEL B. , BOSS ANDERS , JOHNSON JENNAL , DASSAU EYAL 
Published: June 2024

Introduction & Objective: Omission of only three mealtime insulin doses a week is associated with a 1% increase in HbA1c. Retrospective Identification of missed mealtime insulin doses is challenging, but the integration of connected insulin pen (CIP) and CGM data will enable the identification of missed mealtime insulin by healthcare professionals. This study was undertaken to evaluate different approaches to characterize insulin dosing practices.
Method: CIP and CGM data from the Type 1 Diabetes Exercise Initiative study participants (with minimum of 3 recorded insulin injections and 2 meals per day for 190-day period) was analyzed to evaluate methodologies to identify missed mealtime insulin. Three algorithms to identify glucose excursions (MAGE, Delta G, Mo-Delta G) and several insulin dosing windows (before and after onset of the glucose excursion) were examined to evaluate the accuracy and opportunity for intervention.
Results: Analysis of data from 22 subjects (age 34±13; A1c 6.9±0.9% [mean±SD]) meeting inclusion criteria indicated that 12-13% of the 398, 397 and 304 glucose excursions identified with the different algorithms had no insulin recording in a ±2h window from excursion onset.
Conclusions: The integrated analysis of CIP and CGM data provides actionable insights about insulin dosing behavior that could drive improvements in glycemic control in people with T1D.

Disclosure
H. Wolpert: Research Support; Abbott. Consultant; Eli Lilly and Company. J. Xue: Employee; Eli Lilly and Company. C. Chen: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.B. Davidson: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Boss: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Johnson: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. E. Dassau: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
1919-LB: GlucoseReady—Technical Validation of a Novel GxP Platform for Real-Time CGM Capture
Authors: ANDERSON DAVID , MERICKEL MICHAEL , BEST ALLEN , SEVERSON BRIAN T. , DJURHUUS CHRISTIAN B. , GOLDMAN JONATHAN 
Published: June 2024

Introduction: FDA guidance recommends continuous glucose monitoring (CGM) for diabetes clinical trials. Real-time monitoring in such trials demands high-speed data frameworks. Here, we sought to develop a fully GxP-compliant platform that integrates with CGM devices and rapidly transmits regulatory submission quality data to study servers.
Methods: Software acquired glucose readings directly from Dexcom G6 CGM transmitters and sensors via Bluetooth. Live transmitter samples were considered real-time readings; backfill samples were excluded from real-time classification. Software synchronized with study servers after each sample acquisition, pending network connectivity. Descriptive statistics were evaluated for this pilot study.
Results: CGM readings (n=5,996) were generated over a 24 day study period. Median inter-sample interval was 5.0 minutes, and 99.4% of all sample intervals were between 4.9 and 5.1 minutes. Sample validity was high (98.6%), where 1.3% of samples were lost to sensor warmup and 0.05% of samples were lost to sensor error. Real-time measurements made up 96.4% of readings. Median transmitter sync time was 0.50 seconds (IQR: 0.26 - 0.75 seconds). Server upload times were fastest at 12 seconds; median upload time was 10.3 minutes (IQR: 5.3 - 25.3 minutes). Participant showed normal glycemic variability (19.7%), time-in-range (97.3%), and glycemic risk index (3.6%), with few Level-1 (n=3) and Level-2 (n=1) hypoglycemic events.
Conclusions: We developed a fully GxP-compliant high-speed data platform directly integrated with CGM devices. There is potential for low latency data availability - on the order of seconds - and further investigation is required to understand sources of server upload lag, for example network connectivity. Future development of this platform will include integrated hypo forms triggered by CGM data streams. Further work is needed to understand network dynamics of this framework in a larger study cohort.

Disclosure
D. Anderson: Employee; Clinical ink. M. Merickel: None. A. Best: Employee; Clinical Ink. B.T. Severson: Employee; Clinical Ink. C.B. Djurhuus: Stock/Shareholder; Novo Nordisk A/S. J. Goldman: Employee; Clinical ink.
1969-LB: Insulin Deficiency in Women with Early Postpartum Glucose Intolerance
Authors: GITLIN EMILY S. , KULKARNI VANDANA , ALEXANDER MALLIKA , NAIK SHILPA , KOLE ADITI , TAMBE SANJAYKUMAR , DESHPANDE PRASAD , BROWN TODD , MATHAD JYOTI S. , CHEBROLU PUJA 
Published: June 2024

Diabetes during pregnancy (GDM) increases type 2 diabetes (T2DM) risk after delivery. Insulin deficiency postpartum may play a greater role in T2DM development than insulin resistance in South Asian populations due to early life undernutrition and lack of excessive weight gain. We studied insulin pathophysiology after pregnancy in Indian women with GDM. Women were enrolled at delivery and followed until 6 months postpartum at an Indian public hospital serving lower socioeconomic strata. Fasting oral glucose tolerance testing (75 g) with insulin levels at 0, 30, and 120 min at 6 weeks (baseline) and 6 months postpartum were used to assess insulin resistance (by HOMA-IR) and insulin deficiency (by insulinogenic index (IGI) and fasting insulin oral disposition index (oDI)). Prediabetes and T2DM were defined per ADA criteria. Among 49 women at baseline, median age was 28 yrs (IQR 25-32). By 6 months postpartum, 9/49 women (18.4%) had T2DM and an additional 13/49 (26.5%) had prediabetes. IGI and oDI at 6 weeks postpartum were significantly lower in women who had prediabetes/T2DM by 6 months postpartum compared to women with normal glucose tolerance ([0.21 vs 0.48, p=0.03] and [0.03 vs 0.06, p&lt;0.01], respectively), whereas there was no difference in HOMA-IR. Insulin deficiency postpartum may be more predictive of future T2DM than insulin resistance in South Asian women. Larger longitudinal studies are needed to further examine this association.

Disclosure
V. Kulkarni: None. M. Alexander: None. S. Naik: None. A. Kole: None. S. Tambe: None. P. Deshpande: None. T. Brown: Consultant; Merck & Co., Inc., Janssen Pharmaceuticals, Inc., ViiV. J.S. Mathad: None. P. Chebrolu: None.

Funding
Weill Cornell Fund for the Future Grant (R01A162235)
1980-LB: Post-recovery of Acute Hyperglycemia during Hospitalization and Incident Cardiovascular Health Outcomes
Authors: SANTOS MARIA P. , LEY SYLVIA H. 
Published: June 2024

Introduction & Objective: While research links acute hyperglycemia to adverse hospitalization outcomes, post-discharge implications are unclear. We examined the association between acute hyperglycemia during hospitalization and incident cardiovascular health outcomes post-discharge using a large-scale EHR database.
Methods: Using data from the National COVID Cohort Collaborative, we analyzed 5174261 patients in the U.S. with hospital admission between March 1, 2020, and March 1, 2022. Acute hyperglycemia was defined as blood glucose levels exceeding 140 to 180 mg/dL in patients without a pre-existing diabetes diagnosis. Outcomes were defined as physician-diagnosed cerebrovascular disorders, dysrhythmias, inflammatory heart disease, ischemic heart disease, heart failure, and thrombotic disorders ascertained more than 30 d after discharge until end of follow-up on January 31, 2024. HRs were analyzed by Cox regression, adjusted for age, sex, race/ethnicity, hypertension, obesity, coronary artery disease, chronic kidney disease, chronic lung disease, and cardiovascular medication use.
Results & Conclusion: Individuals with acute hyperglycemia during hospitalization faced a higher risk of incident cardiovascular disease (Figure). Those experiencing acute hyperglycemia during hospitalization may benefit from longer-term follow-up focusing on cardiovascular health.

Disclosure
M.P. Santos: None. S.H. Ley: None.

Funding
National Heart, Lung, and Blood Institute of the National Institutes of Health (T32HL158290).
2008-LB: Identification of Genome-Wide Significant Loci for Childhood Glycemic Traits in HAPO Follow-up Study
Authors: DIEGUEZ ABIGAYIL , JOSEFSON JAMI L. , LOWE WILLIAM L. , KUANG ALAN , SCHOLTENS DENISE , GEOFFREY HAYES M. 
Published: June 2024

Introduction & Objective: Type 2 Diabetes (T2D) among children is increasing. Compared to T1D and adult-onset T2D, it is more aggressive with more rapid disease progression. The genetic risk associated with youth-onset T2D has not been elucidated. We performed a GWAS of childhood dysglycemia and precursors to T2D in a diverse youth cohort.
Methods: The Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study (HAPO FUS) cohort, a diverse cohort of children (N=4,160, ages =11-14 years) representing several ancestry groups (African=AFR, Mexican American=AMR, South Asian=SAS, European=EUR, and East Asian=EAS) was used to identify genetic variants associated with glucose dysregulation. The primary outcomes included the lowest quartile of Disposition Index (DI) and Matsuda index (MI), and highest quartile of sum of glucose Z-scores from a fasting 2-hr OGTT (2hGZ). Genome-wide SNP data were imputed to TOPMed. GWAS was performed using an additive model, adjusting for field center, 3 principal components of genetic ancestry, maternal confounders during pregnancy, and offspring confounders during childhood.
Results: We identified two genome-wide significant associations in AFR (intronic in SHOC1 and C8ORF37-AS1) and one in EAS (intergenic between GPIHBP1 and LY6H) with lowest quartile of DI. Four additional genome-wide significant associations were found in AFR (ADI1, MOK, intergenic between SLC37A3 and KDM7A-DT, and intergenic between LINC01541 and GTSCR1) for 2hGZ. One genome-wide significant locus in EAS (intronic in C2CD2) and one in EUR (intronic within INSC) were identified with MI. No associations were identified in our AMR or SAS populations.
Conclusion: Multiple loci were associated with markers of dysglycemia in ancestry-specific analyses of HAPO FUS children. While loci previously reported to be associated with glycemic measures were not identified, subsequent analyses with greater power using trans-ethnic meta-analyses will likely identify additional loci.

Disclosure
A. Dieguez: None. J.L. Josefson: None. W.L. Lowe: None. A. Kuang: None. D. Scholtens: None. M. Hayes: None.

Funding
AD: National Institutes of Health (5T32DK00716JLJ); NIH (R01DK118403MGH: R01DK117491, R01HD100630)
2017-LB: Comparison of Nuclear Preparation for Single-Nucleus RNA-seq of Adipose Tissue
Authors: ONOGI YASUHIRO , WADA TSUTOMU , FUJISAKA SHIHO , SASAOKA TOSHIYASU , IIDA KEITA , OKADA YUKINORI , KADOWAKI MAKOTO , SAITO SHIGERU , TOBE KAZUYUKI 
Published: June 2024

Introduction & Objective: To appreciate the pathophysiological changes in the transcriptome and cell type landscape during obesity, single-nucleus (sn)RNA-seq overcomes the difficulty of maintaining intact transcripts. Sedimentation of dissociated live cells is used to concentrate adipocytes (Ads) and stromal cells. The current study compared the single cell level transcriptome in libraries with and without the fractionation.
Methods: C57BL/6J mice were fed an HFD for 12 weeks starting at 8 weeks of age. Dissected epididymal fat from the same donor was divided into three conditions: 1) nuclei from unfractionated frozen fat (UF), 2) nuclei from the Ad fraction (AF) after enzymatic digestion and centrifugation, and 3) cells from the stromal fraction corresponding to the AF. As a dietary control, nuclei were prepared from the UF of an age-matched normal chow-fed mouse. Single cell/nucleus transcriptome libraries were sequenced using short-read NGS.
Results: A total of 32,949 cells were recovered by snRNA-seq. Fractionation lost recovery of certain cell types, including epithelial, mesothelial, and B cells. Fractionation barely enriched Ads in the AF at 12.4%, comparable to the Ads (11.2%) in the UF. Macrophages (Mφs), rather than Ads, accounted for 54.6% of the AF. The Mφs were clustered into six subtypes by Seurat independent of dietary conditions or fractionation. However, certain cytokines were more highly expressed in Mφs from fractions than those from UF. In support of this, functional annotation-driven unsupervised clustering, ASURAT, mapped three Mφ subtypes in the libraries from fractions that differed from those from the UF, where there were four other subtypes.
Conclusion: The current study suggests that the conventional fractionation could bias the transcriptome and a nuclear library from unfractionated frozen fat would represent a naïve comprehensive transcriptome that better reflects the pathophysiology of obesity, which should be important for understanding cell function.

Disclosure
Y. Onogi: None. T. Wada: None. S. Fujisaka: None. T. Sasaoka: None. K. Iida: None. Y. Okada: None. M. Kadowaki: None. S. Saito: None. K. Tobe: None.

Funding
JST Moonshot R&D (JPMJMS2021)
2018-LB: ABHD17B Modulates Diet-Induced Abdominal Obesity and Chronic Inflammation
Authors: HADLEY JASON , RYU JIYOON , BAI JULI , PAN MEIXIA , BAO HANMEI , HAN XIANLIN , LEADBETTER ELIZABETH , LIU FENG , DONG LILY Q. 
Published: June 2024

Overnutrition induces abdominal obesity and chronic inflammation in humans. Despite the central role of hyperactive pro-inflammatory macrophages, the mechanisms underlying macrophage dysregulation due to overnutrition remains poorly understood. Here, we present the first evidence of the physiological role of ABHD17B, a putative depalmitoylase, in rodents through the generation of whole-body knockout mice and macrophage-specifical knockout mice. Our findings identify macrophages as the primary cellular source of ABHD17B and reveal reduced ABHD17B expression in high fat diet-fed mice. ABHD17B deficiency exacerbates diet-induced abdominal obesity, gut dysfunction, insulin resistance, and inflammation in both knockout mouse models. Furthermore, the loss of ABHD17B amplifies macrophage pro-inflammatory responses and compromises phagocytic efficiency. Mechanistically, ABHD17B de-palmitoylates C5aR2, a pro-inflammatory complement C5a receptor, in macrophages. Deletion of the Abhd17b gene in macrophages enhances the receptor expression and plasma membrane location, stimulates ROS production, and potentiates TLR4-mediated pro-inflammatory signaling. Collectively, our study unveils ABHD17B as a novel anti-inflammatory depalmitoylase crucial for maintaining protein palmitoylation homeostasis in macrophages. Additionally, ABHD17B-C5aR2 signaling emerges as a critical player in safeguarding against over-nutrition induced excessive macrophage inflammation and abdominal obesity.

Disclosure
J. Hadley: None. J. Ryu: None. J. Bai: None. M. Pan: None. H. Bao: None. X. Han: None. E. Leadbetter: None. F. Liu: None. L.Q. Dong: None.

Funding
National Institutes of Health (1R01DK134637-01A1)
2019-LB: The Characteristic Activity of Regulatory B Cells during the Occurrence and Development of Insulin Resistance
Authors: WEI LINGLING , ZHANG LIJIE , MA YAN , ZHAO DONG , YANG LONGYAN 
Published: June 2024

Introduction & Objective: To investigate the aberrant distribution and clinical relevance of regulatory B cells (Bregs) subsets in the peripheral blood of individuals with different levels of insulin resistance (IR).
Methods: A cohort of 124 subjects were divided into five groups according to their insulin resistance index (HOMA-IR) and diabetes diagnosis. The groups comprised HOMA-IR&lt;3 (IR- without T2DM), HOMA-IR&lt;3 (IR- with T2DM), 3≤HOMA-IR&lt;6 (IR+ without T2DM), 3≤HOMA-IR &lt; 6 (IR+ without T2DM) and HOMA-IR≥6 (IR++ with T2DM). Peripheral blood samples were collected from each group, the percentages of CD19+CD24+CD27+ and CD19+CD24+CD38+ Bregs and the levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ were detected by flow cytometry and flow microsphere matrix method. Additionally, the cytokines levels were validated through ELISA. The activation of Bregs and the production of IL-10 among different groups were analyzed. Spearman correlation analysis was used to analyze the correlation between Bregs activation rate and IR degree.
Results: The results showed that the levels of CD19+CD24+CD27+ and CD19+CD24+CD38+ cells were increased whether in IR+ without or with T2DM groups compared to the IR- group, with the most significant increase observed in the IR++ with T2DM group. Moreover, the plasma levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ in the IR+ group were higher than those in the IR- group. The expression and activation level of Bregs were positively correlated with the severity of IR in T2DM.
Conclusion: These results suggest that the increase level of Bregs is closely related to the severity of IR, highlighting the potential significance of Bregs in the clinical progression of Type 2 Diabetes Mellitus (T2DM) and its associated insulin resistance.

Disclosure
L. Wei: None. L. Zhang: None. Y. Ma: None. D. Zhao: None. L. Yang: None.

Funding
This research was funded by Beijing Tongzhou District Science and Technology Plan Project, (KJ2022CX023, KJ2023SS027); Beijing-Tianjin-Hebei Basic Research Joint Project, (22JCZXJC00110) and Cultivation project (PYZ22178) was funded by Capital Medical University.
2020-LB: Immunometabolomics Reveals Little Autoimmunity in Type 1 Diabetes (T1D)—Cross-Sectional Pathway Analysis across Multiple Autoimmune Diseases
Authors: MONEDEIRO FERNANDA , ZÜGNER ELMAR , PRIETL BARBARA , OBERHUBER MONIKA , STRADNER MARTIN , KHALIL MICHAEL , MAGNES CHRISTOPH , PIEBER THOMAS 
Published: June 2024

Introduction & Objective: Metabolic reprogramming has a critical role in the differentiation and function of PBMCs in autoimmune diseases. Here, comparative cellular immune-metabolomics was applied to multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and T1D.
Methods: PBMCs were isolated from healthy individuals (CTRLs, n=10), patients with T1D (n=11), MS (n=8), RA (n=14) and SLE (n=10). Obtained PBMCs were either T cell-stimulated using anti-CD3/CD28 dynabeads or treated with placebo. LC-HRMS metabolomics data was controlled for extraneous variables, submitted to statistical examination and pathway enrichment analysis.
Results: T1D shows a distinct dissimilarity to all tested autoimmune diseases and a striking congruence with controls (Fig.). MS, RA and SLE displayed enhanced metabolism concerning cell growth and death, energetics, transport and catabolism, and signal transduction, while these pathways were only moderately downregulated or not significantly altered in T1D. Metabolome after T cell activation shows a similar but less pronounced pattern.
Conclusion: T1D immune cell metabolome is closely related to that of healthy controls, whereas in MS, RA and SLE several metabolic pathways are highly deregulated. Our findings challenge the concept of immune interventions as monotherapies in T1D.

Disclosure
F. Monedeiro: None. E. Zügner: None. B. Prietl: None. M. Oberhuber: None. M. Stradner: Research Support; Novartis AG. Consultant; Janssen Pharmaceuticals, Inc. Speaker's Bureau; Pfizer Inc., AstraZeneca, Sobi, Eli Lilly and Company, Otsuka America Pharmaceutical, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited. M. Khalil: None. C. Magnes: None. T. Pieber: Advisory Panel; Arecor. Research Support; AstraZeneca. Consultant; Novo Nordisk A/S. Research Support; Novo Nordisk Foundation. Consultant; Lilly Diabetes, Sanofi. Speaker's Bureau; Roche Diabetes Care, Novo Nordisk.

Funding
COMET ? Common Mechanism in Autoimmunity, funded by JDRF and LRA (2-SRA-2021-1043-S-B).