bluuebunny/crossref_metadata_2025_split huggingface dataset:
1437-P: Waist-to-Height Ratio Is a Better Indicator Instead of Waist Circumference for Diagnosing Metabolic Syndrome in Type 2 Diabetes
Authors: KE JIANGFENG , WANG JUNWEI , MA YILIN , WANG YUJIE , LI LIAN-XI 
Published: May 2022

Waist circumference (WC) is currently one of the components of metabolic syndrome (MetS) , but the cutoff points of WC for diagnosing MetS vary between races and genders. Therefore, the aim of this study is to search an anthropometric indicator instead of WC that would be applicable across races and genders. Our previous study found that a waist-to-height ratio (WHtR) &gt;= 0.52 has excellent diagnostic value for MetS in both men and women with type 2 diabetes mellitus (T2DM) . We therefore selected 8525 T2DM patients with complete clinical data in the present study. Agreement between a WHtR &gt;= 0.52 and different WC diagnostic criteria for men (&gt;=90cm) and women (&gt;=80cm) was almost perfect (Kappa=0.911) . As a component of MetS instead of WC, the AUC of new criteria using WHtR to diagnose MetS was 0.963 in T2DM patients. Using a WHtR cut-off of 0.52 most closely associated with the prevalence of MetS in man (98.0% sensitivity and 94.7% specificity) and women (95.7% sensitivity and 98.0% specificity) participants and. Taken together, the use of WHtR instead of WC is a simple and practical indicator for the diagnosis of MetS in T2DM.

Disclosure
J.Ke: None. J.Wang: None. Y.Ma: None. Y.Wang: None. L.Li: None.

Funding
National Natural Science Foundation of China (81770813, and 82070866) .
1439-P: Association between Sleep Duration, Bedtime, and Hyperglycemia or Overweight/Obesity among Japanese Children
Authors: SHIOZAKI HARUKA , FUJIHARA KAZUYA , YAMADA MAYUKO H. , OSAWA TAEKO , KITAZAWA MASARU , MATSUBAYASHI YASUHIRO , YAGUCHI YUTA , YAMAMOTO MASAHIKO , SATO TAKAAKI , YAMADA TAKAHO , SONE HIROHITO 
Published: May 2022

In adults, short sleep duration and late bedtime were associated with hyperglycemia and obesity, but these relationships in children are little known. We evaluated the association of bedtime and sleep duration with overweight/obesity or hyperglycemia in children by sex, considering the effects of diet, physical activity, and screen time. A cross-sectional study was conducted for 1139 Japanese children (553 boys) aged 10-y. Overweight was as defined by the International Obesity Task Force. Cutoff value for hyperglycemia was HbA1c ≥5.6%. Variables associated with hyperglycemia or overweight were based on logistic regression analysis. Multivariate logistic regression analysis showed that compared with an early bedtime (˜21:59) and long sleep duration (weekdays ≥8.67 h, weekends ≥9 h) , short sleep duration (weekdays &lt;8.67 h, weekends &lt;9 h) was associated with overweight in boys but not late bedtimes (22:00˜) . The significant association seen disappeared in girls when adjusted for screen time. For hyperglycemia, in both sexes wake time and sleep duration on weekends were significant in univariate analysis, but not in multivariate analysis adjusted for diet and physical activity. In Japanese boys, short sleep duration was significantly associated with overweight. Sleep ≥8.67 on weekdays and ≥9 h on weekends may be essential to prevent overweight. Table. Adjusted odds ratios for overweight

Disclosure
H. Shiozaki: None. K. Fujihara: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. T. Sato: None. T. Yamada: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding
Patient Centered Outcomes Research Institute
190-OR: Increased Risk of Incident Diabetes after Therapy with Immune Checkpoint Inhibitor Compared with Conventional Chemotherapy: A Longitudinal Trajectory Analysis Using a Tertiary Care Hospital Database
Authors: JEONG KYEONG SEOB , LEE MINYOUNG , PARK YU RANG , RHEE YUMIE 
Published: May 2022

Immune checkpoint inhibitors (ICI) have been emerged as a promising option for cancer treatments. However, ICI use induces immune-related adverse events including diabetes mellitus. We investigated the risk of new-onset diabetes in patients receiving ICI compared with conventional chemotherapy (CC) . Using a tertiary care hospital database, we included cancer patients without previous history of diabetes and treated with either CC or ICI. One-to-five nearest neighbor propensity matching was applied, and the risk for diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed in a trajectory approach to determine distinct clusters following a similar glucose trajectory pattern over time. Of 1,326 subjects, 1,1received CC, and 221 received ICI. The ICI group had a significantly higher cumulative incidence of diabetes compared with those in the CC group (log-rank p &lt; 0.001) . In addition, the risk of new-onset diabetes was significantly increased in the ICI group compared to the CC group (adjusted hazard ratio 2.454, 95% confidence interval 1.528-3.940; p &lt; 0.001) . The proportion of subjects in the trajectory cluster with an increasing glucose pattern was higher in the ICI group than in the CC group (10.4% for the ICI group and 7.4% for the CC group) . Among the ICI group, subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration.
In conclusion, ICI therapy is associated with an increased risk of incident diabetes compared with CC. Glucose levels in the subjects treated with ICI need to be regularly monitored for earlier detection of ICI-associated diabetes, especially males and those with prominent lymphocytosis after ICI treatment.

Disclosure
K.Jeong: None. M.Lee: None. Y.Park: None. Y.Rhee: None.

Funding
Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry of Health & Welfare, Republic of Korea. (grant number: HI19C0189) , and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) , funded by the Korean government (MSIT) (NRF2019M3E5D4064682) .
208-LB: Sensory Nerve Neuropeptide Calcitonin Gene–Related Peptide (CGRP) in Adipose Tissue Changes According to Metabolic Status
Authors: MISHRA GARGI , WILLOWS JAKE 
Published: May 2022

White adipose tissue (WAT) is the chief energy storage site in the body and is densely innervated by sensory and sympathetic nerves that enable bi-directional neural communication with the central nervous system. The sympathetic neurotransmitter norepinephrine is the best-studied nerve product in WAT, and is known to stimulate lipolysis, browning (development of brown adipocytes in WAT) , thermogenesis, and other metabolically favorable processes. Conversely, sensory nerves in WAT secrete neuropeptides such as calcitonin gene related peptide (CGRP) , a vasodilatory neuropeptide that also impacts lipolysis, but has been vastly understudied. Circulating CGRP levels are known to be increased in obese humans, but given the beneficial metabolic effects of CGRP this may be a case of CGRP receptor resistance, similar to the observed leptin and insulin resistance with obesity. Therefore, a more comprehensive investigation into CGRP’s roles in adipose tissue and the importance of the sensory nerve supply for WAT function and insulin sensitivity is warranted. Using intravital calcium imaging in WAT of mice, we have observed activation of tissue nerves after application of lipids such as 13-HODE, which is an agonist of sensory nerves and leads to CGRP release. Thirty minutes after 13-HODE administration to WAT there was a significant increase in CGRP levels in WAT (by tissue ELISA) , which were reduced at 120min post-treatment. This suggests local lipid levels in WAT may trigger release of this sensory neuropeptide as an interoceptive response. With obesity, in both diet-induced and genetic ob/ob mice, we see increased WAT CGRP, which fits with reports in humans and may be due to chronically elevated tissue lipids. Exercise also increases tissue CGRP levels, perhaps due to an acute need for lipid fuels in this negative energy balance state. Taken together, CGRP is a novel factor in adipose that may be relevant for changing energy balance status and likely contributes to metabolic health.

Disclosure
G. Mishra: None. J. Willows: None.
230-OR: Hepatic TORC2 Signaling Facilitates Glucagon-Receptor Enhancement of Insulin-Stimulated Glucose Homeostasis in Mice
Authors: KIM TEAYOUN , NASON SHELLY , ANTIPENKO JESSICA P. , FINAN BRIAN , SHALEV ANATH , DIMARCHI RICHARD , HABEGGER KIRK M. 
Published: May 2022

Long term glucagon receptor (GCGR) agonism is associated with hyperglycemia and glucose intolerance, while acute GCGR agonism enhances whole-body insulin sensitivity and hepatic AKTSer473 phosphorylation. These divergent effects establish a critical gap in knowledge surrounding GCGR action. mTOR Complex 2 (mTORC2) is composed of seven proteins, including RICTOR, which dictates substrate binding and allows for targeting of AKTSer473. We utilized a liver specific Rictor knockout mouse (RictorΔLiver) to investigate whether mTORC2 is necessary for insulin-receptor (INSR) and GCGR crosstalk. RictorΔLiver mice were characterized by impaired Akt signaling and glucose intolerance. Intriguingly, RictorΔLiver mice were also resistant to GCGR-stimulated hyperglycemia. Consistent with our prior report, GCGR agonism increased glucose infusion rate and suppressed hepatic glucose production during hyperinsulinemic-euglycemic clamp of control animals. However, these benefits to insulin sensitivity were ablated in RictorΔLiver mice. We observed diminished AKTSer473 and GSK3α/β Ser21/9 phosphorylation in RictorΔLiver mice, whereas phosphorylation of AKTThr3was unaltered in livers from clamped mice. These signaling effects were replicated in primary hepatocytes isolated from RictorΔLiver and littermate control mice, confirming cell autonomous crosstalk between GCGR and INSR pathways.
In summary, our study reveals the necessity of RICTOR, and thus mTORC2, in GCGR-mediated enhancement of liver and whole-body insulin action.

Disclosure
T.Kim: None. S.Nason: None. J.P.Antipenko: None. B.Finan: Employee; Novo Nordisk. A.Shalev: None. R.Dimarchi: None. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Glyscend Inc.

Funding
1R01DK112934P30DK079626
234-OR: Noninvasive Hypoglycemia Detection during Real Car Driving Using In-Vehicle Data
Authors: LEHMANN VERA , ZUEGER THOMAS , MARITSCH MARTIN , NOTTER MICHAEL , SCHALLMOSER SIMON , BÉRUBÉ CATERINA , ALBRECHT CAROLINE , KRAUS MATHIAS , FEUERRIEGEL STEFAN , FLEISCH ELGAR , KOWATSCH TOBIAS , LAGGER SOPHIE N. , LAIMER MARKUS , WORTMANN FELIX , STETTLER CHRISTOPH 
Published: May 2022

Aim: To develop a non-invasive machine learning (ML) approach to detect hypoglycemia during real car driving based on driving (CAN) , and eye and head motion (EHM) data.
Methods: We logged CAN and EHM data in 21 subjects with type 1 diabetes (18 male, 41 ± yrs, A1c 6.8 ± 0.7 % [51 ± 7 mmol/mol]) during driving in eu- (EU) and hypoglycemia (&lt; 3.0 mmol/L, HYPO) . Participants drove in a car (Volkswagen Touran) supervised by a driving instructor on a closed test-track. Using CAN and EHM data, we built ML models to predict the probability of the driver being in HYPO. To make our approach applicable to different generations of cars, we present 3 ML models: first, a model combining CAN+EHM, representing the modern car with integrated camera. Second, a CAN model using driving data only, since modern cars are not generally equipped with EHM tracking. Third, anticipating that autonomous driving will limit the role of CAN data in the future, we tested a model solely based on EHM.
Results: Mean BG in EU and HYPO was 6.3 ± 0.8 mmol/L and 2.5 ± 0.5 mmol/L (p&lt; 0.001) , respectively. The model CAN+EHM achieved an area under the receiver operating characteristic curve of 0.88 ± 0.05, sensitivity of 0.70 ± 0.30, and specificity of 0.83 ± 0.in detecting HYPO. Further results are in Fig. 1.
Conclusion: We propose ML-based approaches to non-invasively detect HYPO from driver behavior, applicable to contemporary cars and anticipating developments in automotive technology.

Disclosure
V.Lehmann: None. E.Fleisch: None. T.Kowatsch: Advisory Panel; Pathmate Technologies AG, Research Support; CSS Insurance, Stock/Shareholder; Pathmate Technologies AG. S.N.Lagger: None. M.Laimer: None. F.Wortmann: None. C.Stettler: None. T.Zueger: None. M.Maritsch: None. M.Notter: None. S.Schallmoser: None. C.Bérubé: None. C.Albrecht: None. M.Kraus: None. S.Feuerriegel: None.

Funding
Swiss National Science Foundation (SNF CRSII5_183569) , Swiss Diabetes Foundation, Diabetes Center Berne, Automobile Club Switzerland (ACS) , Federal Department of Defence, Civil Protection and Sport (DDPS) and Department of Research of the University Hospital Berne
245-LB: An Ankyrin-B–Mediated Protein Chaperone Mechanism Modulates Pancreatic ß-Cell Susceptibility to Proteotoxicity-Induced ER Stress and Apoptosis
Authors: TZENG JOYCE , HOHMEIER HANS-EWALD , LORENZO DAMARIS 
Published: May 2022

Impaired insulin secretion contributes to the development and progression of diabetes. β-cells initially cope with the genetic, environmental, and diabetogenic stresses that diminish insulin secretion or the peripheral response to it by increasing insulin production. However, sustained increases in the insulin precursor proinsulin (PI) place additional demand on the secretory and protein quality control (PQC) machineries of β-cells, triggering endoplasmic reticulum (ER) and oxidative stress, mitochondrial dysfunction, and β-cell death. Thus, understanding the mechanisms that regulate β-cell responses to increased insulin secretory requirements is critical to prevent β-cell failure. We reported that the cytoskeletal scaffolding protein ankyrin-B (AnkB) regulates insulin secretion by maintaining normal levels of the inositol-1,4,5-triphosphate receptor (IP3R) at the ER and intracellular calcium in β-cells. IP3R levels and insulin secretion were impaired in knock-in mice carrying the p.R1788W AnkB (AnkB-RW) variant associated with type 2 diabetes (T2D) in Caucasians and Hispanics. Here, we show that selective loss of AnkB or expression of the T2D AnkB-RW variant lead to reduced insulin secretion and accumulation of PI and islet specific amyloid polypeptide in β-cells. These changes are accompanied by enhanced induction of the maladaptive unfolded protein response and apoptosis. Interestingly, the T2D AnkB-RW variant lies within the binding site for the protein chaperone Dnajb1 (Hsp40) . Our results indicate that the Dnajb1-Hspa1a complex, which recognizes and delivers protein clients to Hsp70 chaperones to promote proper folding, refolding, or degradation, is downregulated in β-cells from β-cell-specific AnkB knockout or AnkB-RW mice. Increased proteotoxicity and reduced insulin secretion were also observed upon knockdown of Dnajb1 in rat INS1 832/13 cells. Together, our findings suggest that AnkB and its integration into the Dnajb1-Hspa1a pathway modulates PQC and promotes β-cell survival under diabetogenic conditions.

Disclosure
J. Tzeng: None. H. Hohmeier: None. D. Lorenzo: None.
254-LB: EndoC-ßH5 Human Beta Cells—A Unique “Thaw and Go” Model for Accelerating Diabetes Research with Highly Functional and Ready-to-Use Human Beta Cells
Authors: OLLEIK HAMZA , BLANCHI BRUNO 
Published: May 2022

In 2021, 537 million adults were living with diabetes worldwide (90% T2D) , a number that is predicted to rise to 643 million by 2030. The need for physiologically relevant human cellular models to study human beta cell function, insulin secretion and diabetes is thus greater than ever. To date, human pancreatic islets present many drawbacks related to lack of availability and reproducibility that limit their use. While animal models remain far from human reality. Newly developed EndoC-βH5® cells represent an extremely promising tool both for drug discovery and disease modeling. They take the best out of native cells from which they were derived, with high sensitivity to physiological concentrations of glucose and robust response to insulin secretagogues. They also leave the rest, thanks to direct availability as frozen stocks, ready-to-use format, batch-to-batch reproducibility and maintaining stable function for weeks. Specifically, EndoC-βH5® is a pure population of insulin expressing cells (100% INS/92.3% PDX1/90% NKX6.1) . Insulin content is close to that of native pancreatic beta cells (&gt; 5µg/million cells) . EndoC-βH5® cells dose dependently respond to physiological concentrations of glucose (highest potentiation of insulin secretion between 2.8 and 8 mM glucose) with elevated absolute insulin secretion values (hundreds of ng/hr/106 cells) similar to native islets. Furthermore, they dose dependently respond to GLP1R agonists, GIPR agonist, and dual agonist Tirzepatide® with reproducible EC50 and increased insulin secretion &gt;3-fold over high glucose. In addition, Endoc-BH5® cells can be assayed in 384-well plates paving the way for HTS and have been validated as 3D spheroids with extremely robust functional data. Finally, expression of diabetes related genes can be modified to produce relevant disease models. Overall, EndoC-βH5® represent a novel human pancreatic beta cell solution with very high potential for developing human diabetes models, unraveling diabetes mechanisms in human cells and developing antidiabetic drugs.

Disclosure
H. Olleik: None. B. Blanchi: None.
284-OR: Diabetes Technology Access for Youth with T1D and High Social Risk: Comparing Intervention Outcomes
Authors: LELY JUSTINE , HARRIS MICHAEL A. , NARANJO DIANA , JENISCH CELESTE , MANABAT ANN JELINE F. , CRUZ CRISTIAN , BENSEN RACHEL , OSPINA ANDREA BONILLA , WAGNER DAVID V. 
Published: May 2022

Objective: Health disparities exist in diabetes technology access for those youth with T1D who experience high social risk, despite likely benefits. Novel Interventions in Children’s Healthcare (NICH) , designed to improve health for youth with T1D experiencing such disparities, has previously been associated with improved diabetes technology access. This study compares diabetes technology use prior to and after NICH referral, and is the first such study to include a control group.
Methods: Youth with T1D served by NICH (n=65) and referred youth (“controls”: n=73) across 3 sites were included. EHR data included DKAs, hospitalizations, ED visits, and presence of diabetes technology 1 year prior and 2 years after NICH initiation. No significant demographic differences.
Results: Compared to the controls, NICH youth were significantly more likely to gain a CGM and experience significantly greater reductions in hospital admits, DKAs, and ED visits. After accounting for prior differences, only DKA event reduction and CGM access continued to be significant. Youth in NICH also averaged more years with tech access.
Conclusion: This study demonstrates that while youth referred to NICH experience substantial barriers to accessing diabetes technology, youth in NICH were more likely to gain CGM access and have fewer DKA events than controls - and neither group approached national averages in technology access.

Disclosure
J.Lely: None. M.A.Harris: None. D.Naranjo: None. C.Jenisch: None. A.F.Manabat: None. C.Cruz: None. R.Bensen: None. A.Bonilla ospina: None. D.V.Wagner: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
298-OR: Variant-to-Gene Mapping at the Childhood Obesity Locus on chr12q13 and Subsequent Luciferase Assay Analyses Implicate rs71329as a Causal Variant within the 3’ UTR of FAIM2
Authors: LITTLETON SHERIDAN H. , BRADFIELD JONATHAN , PIPPIN JAMES A. , SU CHUN , CHESI ALESSANDRA , WELLS ANDREW D. , BERKOWITZ ROBERT I. , PAHL MATTHEW C. , GRANT STRUAN F. 
Published: May 2022

A key limitation of genome-wide association studies (GWAS) is that they do not specify either the underlying causal variant (s) or the effector gene (s) at a given locus. The widely reproduced obesity FAIM2 locus, named arbitrarily after the nearest gene, is relatively understudied given it is more strongly associated in children than in adults. Our previously reported trans-ancestral GWAS meta-analysis of childhood obesity enabled fine-mapping of the FAIM2 locus; in the ‘credible set’ of 6 SNPs, rs71329 had the highest probability of being causal. This non-coding variant resides in the 3’ untranslated region (UTR) of FAIM2. Given that obesity-related GWAS signals have been reported to be enriched in genes relevant to neuronal function, we generated ATAC-seq and high-resolution promoter-focused Capture C data in both primary astrocytes and ESC-derived hypothalamic neurons to carry out variant-to-gene mapping at this locus. We observed that rs71329 occupied a region of open chromatin, therefore a putatively functional element, and made physical contact with the FAIM2 promoter. These findings were also supported by both GTEx testes eQTL data and a transcriptome-wide association study in brain tissue. We sought to determine in vitro if the rs71329alleles influence enhancer activity in primary astrocytes. Using technical replicates repeated 8 times, the non-risk allele region increased luciferase reporter expression relative to the FAIM2 promoter alone by a fold change of 1.87, while the risk allele decreased expression by a fold change of 0.68 (non-risk allele+FAIM2 promoter vs. risk allele+FAIM2 promoter P&lt;0.0001) . Our results show that rs71329resides in an enhancer element and suggest that the risk allele within the 3’ UTR of FAIM2 decreases the expression of this putative effector gene, which then confers risk of childhood obesity and in turn type 2 diabetes later in life.

Disclosure
S.H.Littleton: None. J.Bradfield: None. J.A.Pippin: None. C.Su: None. A.Chesi: None. A.D.Wells: Stock/Shareholder; Johnson & Johnson. R.I.Berkowitz: Research Support; Eisai Inc., Novo Nordisk. M.C.Pahl: None. S.F.Grant: None.

Funding
National Institutes of Health (HD056465)