bluuebunny/crossref_metadata_2025_split huggingface dataset:
1331-P: Associations between Insulin Resistance and Plasma Lipids and Metabolomics in Women with and without Type 1 Diabetes
Authors: VIGERS TIMOTHY B. , PYLE LAURA , SCHAUER IRENE E. , BERGMAN BRYAN C. , SNELL-BERGEON JANET K. 
Published: May 2022

Insulin resistance (IR) increases risk for cardiovascular disease and mortality in people with type 1 diabetes (T1D) . We previously found associations between plasma lipids, metabolites and IR; whether these associations differ in people with and without T1D is not well understood.
We analyzed targeted plasma lipidomics and untargeted plasma metabolomics in 25 premenopausal women aged 18-45 yrs (12 with T1D and 13 without diabetes [non-DM]) who had a hyperinsulinemic euglycemic clamp to measure glucose infusion rate (GIR) . After stratifying by diabetes, women were classified by tertiles of GIR. We used sparse partial least-squares discriminant analysis to predict and moderated t-tests to compare most IR vs. most insulin sensitive (IS) tertile.
Among women with T1D, 3 lipids, 4 amino acids, 3 peptides, 3 xenobiotics, 1 carbohydrate, and 1 nucleotide were lower and 1 lipid and 1 fatty acid were higher in the most IS tertile (Table) . Among non-DM women, 4 lipids, 1 cofactor, 1 fatty acid, and 1 phosphatidylethanolamine were lower and 1 nucleotide and 1 lipid were higher in the most IS tertile. None of the top features were the same in the T1D and non-DM groups.
Plasma lipids and metabolites were differentially associated with IR in women with and without T1D. Future work should validate these findings in a larger sample of women and men, and explore how these biomarkers relate to IR and metabolism in T1D.

Disclosure
T.B.Vigers: None. L.Pyle: None. I.E.Schauer: None. B.C.Bergman: Research Support; Eli Lilly and Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.

Funding
American Diabetes Association (7-13-CD-10) ; National Heart, Lung, and Blood Institute (grant HL61753 and HL113029) , JDRF Diabetes Foundation (grant 17-2013-313) , DERC Clinical Investigation Core (grant P30 DK57516) , NIH-M01-RR00051, NIH P30-DK116073
134-OR: Cost-Effectiveness of a Real-Time Continuous Glucose Monitoring System vs. Self-Monitoring of Blood Glucose in Type 2 Diabetes Patients on Insulin in Canada
Authors: ISITT JOHN J. , ROZE STEPHANE , COGSWELL GREGORY , LYNCH PETER M. 
Published: May 2022

A health economic analysis was conducted to determine the cost-effectiveness of a real-time continuous glucose monitoring (rt-CGM) system versus self-monitoring of blood glucose (SMBG) in Type 2 diabetes (T2D) patients treated with insulin. The IQVIA CORE diabetes model was utilized for the analysis. Clinical data were sourced from a US retrospective cohort study of adult T2D patients on insulin and adapted to Canada. The baseline mean age (SD) of the cohort was 61 years (13.2) and proportion of male 49%. Mean baseline HbA1c for the cohort was 8.3% (67 mmol/mol) . Patients using rt-CGM were assumed to have a reduction in HbA1c of -0.56% based on the mean difference between groups after 12-months follow-up. A quality-of-life (QoL) benefit associated with reduced finger-stick testing was applied. The analysis was conducted from the Canadian Agency for Drugs and Technologies in Health perspective over a lifetime horizon. The rt-CGM system was associated with an incremental gain of 0.97 quality-adjusted life years (QALYs) compared with SMBG (mean [SD] 10.35 [3.08] versus 9.375 [2.85] QALYs) . Total mean [SD] lifetime costs were CAN$ 17,223 higher with rt-CGM (CAN$ 206,284 [121,493] versus 189,061 [129.680]) , resulting in an incremental cost-effectiveness ratio of CAN$ 17,652 per QALY gained. Sensitivity analyses demonstrated findings were sensitive to changes in QoL, HbA1c, younger patient cohorts, and rt-CGM cost. Varying rt-CGM cost to -25% of base case yielded an ICER of CAN$ 3,512, and varying rt-CGM cost to -50% of base case the ICER becomes dominant over SMBG. For T2D patients on insulin, rt-CGM was associated with significant clinical outcomes and is a cost-effective management option relative to SMBG based on a willingness-to-pay threshold of CAN$ 50,000 per QALY gained.

Disclosure
J.J.Isitt: Consultant; Dexcom, Inc. S.Roze: None. G.Cogswell: None. P.M.Lynch: Employee; Dexcom, Inc., Stock/Shareholder; Dexcom, Inc.
1366-P: Examining Central Carbon Metabolic Flux in the Perfused Exocrine Pancreas Using Dissolution Dynamic Nuclear Polarization
Authors: RUSHIN ANNA , MCLEOD MARC , RAGAVAN MUKUNDAN , MERRITT MATTHEW 
Published: May 2022

The pancreas functions as both an endocrine and exocrine gland. The endocrine component consists of the islets of Langerhans, whereas the exocrine tissue produces digestive enzymes through the ductal system. Although the majority of Type I Diabetes research has focused on the islets, the exocrine tissue is likely implicated in T1D as well. This research utilizes a novel method to investigate exocrine pancreas metabolism with a pancreas perfusion system. I hypothesized that dissolution dynamic nuclear polarization (dDNP) combined with the pancreas perfusion system would provide real-time measurements of central carbon metabolic turnover in the exocrine pancreas. DNP is a phenomenon in which a transfer of high spin polarization greatly enhances the signal in the resulting nuclear magnetic resonance (NMR) spectra. This research compares dDNP measurements in the exocrine pancreas in C57BL/6 male mice under varying glucose conditions. It also examines central carbon metabolism using this system in the T1D mouse model NOD.Rag1-/-.AI4α/β and the NOD.Rag1-/- control. After cannulation of the common bile duct, the exocrine pancreas was perfused for 30 minutes with perfusate containing either 3mM or 16.7mM glucose. Tissue viability was confirmed throughout the perfusion with oxygen consumption measurements. dDNP was performed using the trityl radical and 4mM [1-13C]pyruvate. NMR spectra were collected on a 600MHz instrument with a 10mm [13C]-optimized cryoprobe and analyzed with Bruker TopSpin. Several metabolites were identified and quantified in all measured spectra, demonstrating the detection of real-time metabolic turnover. Ultimately, this work demonstrates that dissolution dynamic nuclear polarization can be used to evaluate metabolic flux in the pancreas in multiple mouse models. Future will investigate the real-time metabolic response of the exocrine pancreas to insulin concentrations in the T1D disease model.

Disclosure
A.Rushin: None. M.Mcleod: None. M.Ragavan: None. M.Merritt: None.

Funding
National Institutes of Health (T32 DK10876) National Science Foundation (DMR-1644779)
1367-P: A Submembrane Cytoskeleton-Dependent Mechanism Modulates Mitochondrial Homeostasis and Skeletal Muscle Bioenergetics
Authors: VOOS KAYLEIGH , TZENG JOYCE , CHOI HA EUN , PHARR TREVOR , LORENZO DAMARIS 
Published: May 2022

Human variants in the ubiquitously expressed cytoskeletal scaffolding protein Ankyrin B (AnkB) , which is enriched in skeletal muscle (SKM) , have been identified as risk factors for diabetes and obesity. Mice harboring pathogenic variants exhibit reductions in levels of the predominant 220-kDa AnkB isoform in several tissues, including SKM and impaired systemic glucose regulation. To understand the specific metabolic role of AnkB in SKM, we developed a conditional knock-out mouse in which 220-kDa AnkB is knocked out only in SKM (SKM-AnkB-KO) . SKM-AnkB-KO mice display glucose mishandling that persists with age, as well as decreases in activity and exercise capacity, measured by indirect calorimetry and voluntary running wheel analysis. Histological evaluations of aged SKM-AnkB-KO mice showed general disorganization of muscle fibers and the presence of centralized nuclei. This is accompanied by increases in lean muscle mass and in the cross-sectional area of mitochondria-rich soleus muscle, suggesting the development of muscle hypertrophy over time. Electron microscopy analysis revealed the presence of hyperfused mitochondria in SKM-AnkB-KO mice. This morphological change was concomitant with up-regulation of transcripts in pathways associated with energetic stress, including AMPK signaling, redox signaling and mTOR signaling, assessed by RNA-seq, and with alterations in mitochondrial respiration in isolated muscle fibers. Interestingly, SKM-AnkB-KO mice mi SKM-AnkB-KO mice also exhibit increases in protein levels of electron transport chain proteins. Through proteomics and biochemical analysis, we uncovered that AnkB directly associates with several mitochondrial proteins and co-fractionates with mitochondrial in SKM. Together, these data suggest a direct role of AnkB in SKM mitochondrial metabolism that is distinct from its previously characterized role in insulin signaling in other tissues and cytoskeletal organization in SKM.

Disclosure
K.Voos: n/a. J.Tzeng: None. H.Choi: None. T.Pharr: None. D.Lorenzo: None.

Funding
American Diabetes Association; National Institutes of Health (1T32GM119999-01A1)
1371-P: Dynamic Mapping of Skeletal Muscle Perfusion and Phosphocreatine with 1H Magnetic Resonance Imaging: A Rest-Exercise Study in Diabetes
Authors: WAHIDI RYAN , LI RAN , ZAYED MOHAMED A. , HASTINGS MARY , ZHENG JIE 
Published: May 2022

Aim: Evaluating time and spatially resolved 1H magnetic resonance imaging (MRI) in quantifying muscle tissue phosphocreatine (PCr) kinetics (without extra hardware) and perfusion in healthy individuals and patients with type 2 diabetes mellitus (DM) .
Methods: 18 subjects were imaged in 3 groups using a 3T MRI scanner; young healthy (26y, n= 6) , old healthy (62y, n = 6) , and DM patients (66y, n = 6) . For each subject, a chemical exchange saturation transfer (CEST) MRI scan was performed in the calf every 1 min at rest (3 min) , during exercise (4 min standardized isometric plantarflexion) , and a recovery period (6 min) . Subjects also underwent mapping of skeletal muscle perfusion in a separate exercise protocol. PCr concentration maps were quantified by Bloch-McConnell fitting, and values were obtained in the medial gastrocnemius and soleus muscles.
Results: DM patients show a longer PCr recovery time τ during recovery compared to both healthy groups: young healthy τ = 47.1 ± 18.2s, old healthy τ = 41.9 ± 15.1s, and DM τ =122.2 ± 58.6s, p = 0.02 (Figure) . There is a negative correlation between PCr and perfusion during exercise in healthy groups (r = 0.38, p = 0.034) that is not significant in the DM group.
Conclusion: Dynamic PCr mapping by proton MRI in calf muscle reveals impaired energetics that is uncoupled from muscle perfusion in DM compared to healthy controls.

Disclosure
R.Wahidi: None. R.Li: None. M.A.Zayed: None. M.Hastings: None. J.Zheng: None.
1382-P: Novel Mechanisms to Reconvert Glucocorticoids into Pro-Metabolic Agents through Adiponectin
Authors: WINTZINGER MICHELLE , MIZ KAREN , PANTA MANOJ , DURUMUTLA HIMA BINDU , PRAGASAM ASHOK DANIEL PRABAKARAN , QUATTROCELLI MATTIA 
Published: May 2022

Adiponectin is the most abundant adipokine in our circulation and regulates inter-tissue communication like the adipose-muscle axis. Pharmacological modulation of this crosstalk is beneficial in promoting exercise tolerance in metabolic stress conditions like obesity. Endogenous glucocorticoids regulate metabolic function and stress response, but chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. However, in stark contrast to daily intake, we discovered that intermittent regimens of glucocorticoids, e.g. once-weekly, improves exercise tolerance. However, the mechanisms underlying the differential regimen-specific effects of glucocorticoids in obesity remain unknown. Here we investigated the mechanisms differentiating once-weekly versus once-daily regimens of the same glucocorticoid prednisone in obesity. In mice with diet-induced obesity, once-weekly prednisone stimulated total and high-molecular weight adiponectin levels, improving exercise tolerance and energy expenditure. These effects were dependent upon adiponectin and were blocked by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the adipose-specific glucocorticoid receptor (GR) , as this effect was blocked in mice with inducible GR ablation in adipose tissue. In contrast, once-daily prednisone decreased adiponectin levels through upregulation of known repressors of adiponectin expression in adipose tissue. The drug regimens remodeled in opposite ways also transcriptome and function in skeletal muscle after onset of obesity. Particularly, once-weekly prednisone treatment increased the muscle metabolic response to adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity through direct upregulation of adiponectin expression in adipose tissue and adiponectin-dependent signaling in skeletal muscle.

Disclosure
M.Wintzinger: Employee; Cincinnati Children's Hospital. K.Miz: None. M.Panta: None. H.Durumutla: None. A.Pragasam: None. M.Quattrocelli: None.

Funding
National Institutes of Health grant DK121875National Institutes of Health grant HL158531CCHMC Trustee AwardCCHMC Heart Institute Translational Grant
1386-P: Confirmation of the Criteria for Insulin Administration at the Start of Steroid Therapy
Authors: KANEKO SHIZUKA , MOTOHASHI KAZUYA , MINAMI TOMOKO , UEBA YOKO , OSUGI TOMOAKI , TOKUMOTO SHINSUKE 
Published: May 2022

Blood glucose elevates at initial high-dose steroid (HDS) administration and is prolonged by persistent amplification of glucagon-induced glycogenesis. Insulin (INS) administration at initial dose of HDS will avoid this. However, INS administration criteria regarding BS elevation are not defined. HDS were given based on COVID-treatment guidelines. HDS administration circumstances in clinical settings may clarify these criteria. The necessity of INS therapy at initial HDS administration is studied. COVID-inpatients receiving HDS, regarding a COVID-period in Japan comprising 5 waves, were sub-grouped into those requiring INS therapy and those not, and analyzed with respect to age, BMI, fasting blood glucose (FBS) , A1c, C-peptide (CPR) index, CPR/glucagon (GCG) . INS was administered, target BS level 200 mg/dL or less at 14:00, depending on BS level after HDS administration. From 396 patients, 257 received HDS as follows, 1of the 154 patients in Wave 1-3 (69.5 ± 16.7 years, BMI 23.9 ± 4.8%, A1c 6.3 ± 1.1%) , 79 of the 83 patients in Wave 4 (64.5 ± 14.6 years, BMI 24.9 ± 4.78, A1c 6.6 ± 1.1%) , and 73 of the 117 patients in Wave 5 (54.4 ± 15.2 years, BMI 25.2 ± 5.1, A1c 6.2 ± 0.8%) . Of the 257 patients above, 145 were treated with INS. In all Waves, only FBS and A1c differed significantly between INS-treated and non-INS-treated patients. ROC analysis in Wave 1-3, Wave 4 and Wave 5 showed cut-off values of A1c (sensitivity/specificity) and FBS (sensitivity/specificity) measuring 6.1% (0.85/0.62) and 121.5 mg/dL (1.00/ 0.62) , 6.5% (0.44/0.83) and133.5 mg/dL (0.40/0.93) , and 6.4% (0.49/1.0) and 112.5 mg/dL (0.81/0.85) , respectively. In patients with FBS levels of 112.5 mg/dL or higher or A1c levels of 6.3% or higher, the use of INS from the initial HDS administration reduced prolongation of hyperglycemia. Variables BMI, CPR, and GCG secretion cannot determine the need for INS therapy. It is important to use FBS and A1c levels, according to conventional practice, to ascertain if INS administration is necessary.

Disclosure
S.Kaneko: None. K.Motohashi: None. T.Minami: None. Y.Ueba: None. T.Osugi: None. S.Tokumoto: None.

Funding
Reiwa 2nd year cookie test clinical research grant
1388-P: Pancreatic Neural Circuitry in Obesity and Diabetes
Authors: HAMPTON ROLLIE F. , ALVARSSON ALEXANDRA , GONZALEZ MARIA JIMENEZ , LI ROSEMARY Y. , DEVARAKONDA KAVYA , STANLEY SARAH 
Published: May 2022

Background: Pancreatic islets are richly innervated. Use of 2D immunohistochemistry and extreme models of obesity and diabetes have limited our understanding of pancreatic nerve anatomy. Additionally, our knowledge of the direct roles of pancreatic nerves in regulating pancreatic function is incomplete. Determining how high-fat diet (HFD) impacts pancreatic nerve structure and function will provide novel insights into the mechanisms and pathophysiology of obesity and type 2 Diabetes.
Aim: To create a comprehensive atlas of pancreatic sympathetic and parasympathetic fibers throughout the pancreas and the time course of HFD-induced structural changes and to determine the direct physiological roles of pancreatic efferent nerves on islet hormone secretion. Hypothesis: HFD increases islet sympathetic density and activity, while decreasing islet parasympathetic density and activity, leading to insufficient plasma insulin to maintain normoglycemia.
Methods: C57BL/6 mice were randomized to HFD or low-fat diet (LFD) groups. Weekly metabolic phenotyping was determined. Pancreata were cleared and immunolabeled according to iDISCO+, imaged by lightsheet microscopy, and analyzed using Imaris software. To test the roles of pancreatic parasympathetic nerves on islet hormone release, cre-dependent hM3D (Gq) -mCherry or mCherry viral constructs were injected into the pancreatic duct of ChAT-IRES-cre mice. ChAT-IRES-cre mice were fed LFD or HFD and the effects of neuromodulation were assessed.
Results: HFD significantly impairs glucose tolerance and insulin sensitivity and rapidly remodels islet sympathetic and parasympathetic innervation. Targeted activation of pancreatic parasympathetic efferent nerves significantly improves glucose tolerance after HFD consumption.
Conclusion: HFD rapidly remodels pancreatic innervation which may contribute to insufficient insulin release to maintain normoglycemia. Targeted activation of pancreatic parasympathetic nerves improves glycemic control.

Disclosure
R.F.Hampton: None. A.Alvarsson: None. M.Jimenez gonzalez: None. R.Y.Li: None. K.Devarakonda: None. S.Stanley: None.

Funding
NIH F31 Predoctoral Fellowship (1F31DK129016-01A1)
1389-P: Asprosin-Neutralizing Antibodies as a Treatment for Binge Eating
Authors: HARMS JERNEY , FENG BING , VIDRINE JACOB , XU PINGWEN , HE YANLIN 
Published: May 2022

The central nervous system (CNS) circuits that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. Here, we provide evidence to support the vital role of asprosin, a novel fasting-induced glucogenic and orexigenic hormone, in the development of binge eating. We found that heterozygous deletion of fibrillin 1, the gene encoding asprosin protein, led to a 50% decrease in asprosin production and reduced binge-like eating behavior in mice. Consistently, systemic treatment of asprosin promoted, while an asprosin-neutralizing antibody inhibited, binge-like eating behavior. These behavioral changes were associated with increased or decreased activity of gamma-aminobutyric acid (GABA) producing neurons in the zona incerta (ZI) brain region, respectively. Mechanistically, we further demonstrate that asprosin stimulates ZI GABA neurons by decreasing small-conductance, calcium-activated potassium (SK) currents. Conversely, the asprosin-neutralizing antibody inhibits ZI GABA neurons by increasing SK currents. Our results support a model that asprosin decreases SK currents to stimulate ZI GABA neurons, further promoting binge-like eating behavior and causing obesity in mice. Our findings also provided preclinical evidence that asprosin-neutralizing antibodies could be used to treat binge eating.
Keywords: Asprosin, neutralizing antibody, binge eating, obesity, GABA neurons

Disclosure
P. Xu: None. Y. He: None.

Funding
National Institutes of Health (P30 DK072476)
139-LB: Evaluating the Impact of Quality Initiatives on Improving Insulin Pen and Needles Prescription on Hospital Discharge in Patients with Type 2 Diabetes Mellitus
Authors: MOAZZAMI BOBAK , HWANG PATRICIA , ASHRAF SHANZA , PROOYEN AMANDA VAN , SHABBIR HASAN F. , KLIMENKO MARIA , BRECHTELSBAUER ERIKA , MOLITCH-HOU ETHAN , HINDS MAUREEN A. , WALD MARY , JAGANNATHAN RAM , GALINDO RODOLFO J. 
Published: May 2022

Background: Prescribing insulin pens without needles during hospital discharge was common in our hospital system. We assessed the impact of quality initiatives and prescribing guidance on the prevalence of patients discharged on insulin pens with and without an associated prescription for pen needles.
Methods: We retrospectively collected data from Emory-healthcare hospitals, from January 2015-May 2018 (pre-intervention period) , then up to October 2021 (post-intervention period) . Adults (&gt;18 years) with at least one prescription for insulin pens were included. As part of an updated discharge plan, an automated EMR alert was linked to orders for insulin pens without needles, aiming to reduce prescription errors at discharge. We compared the proportion of patients discharged on insulin pens with/without an associated pen needles prescription during the pre and post-intervention periods. We used interrupted time-series analysis (ITS) to examine the intervention impact on 30- and 90-day hospital readmissions.
Result: Among 7654 patients discharged with insulin pens (median age 56 years, IQR 45-66) , 50.4% were Females, 65.5% were African-Americans, and mean HbA1c was 10.9±2.9%. After the intervention, the proportion of patients without an associated prescription for pen needles decreased compared to the pre-intervention (mean decrease 31.3%, 95% CI: 31.2%, 31.3%) . Inpatient diabetes education consult was more common among those with an associated pen needles prescription during the pre- (61.4% vs. 33.7%) and post-intervention period (64.7% vs. 33%) , compared to those without it, p&lt;0.001. After the intervention, there was a significant improvement in 90-days hospital readmission rates (-0.99% per quarter; P&lt;0.005) , whereas the change in slope was not significant for 30-day hospital readmission rates.
Conclusion: Our initiative significantly decreased the prevalence of missing pen needles prescriptions by ∼30%, and was associated with less 90-days hospital readmission rates.

Disclosure
B. Moazzami: None. M. Wald: None. R. Jagannathan: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. P. Hwang: None. S. Ashraf: None. A. Van prooyen: None. H. F. Shabbir: None. M. Klimenko: None. E. Brechtelsbauer: None. E. Molitch-hou: None. M. A. Hinds: None.