bluuebunny/crossref_metadata_2025_split huggingface dataset:
184-LB: The Effect of Early Screening and Intervention for Gestational Diabetes Mellitus on Pregnancy Outcomes—The TESGO Randomized Controlled Trial
Authors: KUO CHUN-HENG , LIN SHIN-YU , LIN MING-WEI , LEE CHIEN-NAN , CHANG CHIN-HAO , HAN CHANG YU , TAI YI-YUN , CHEN SAIGE , WENG YEN I , FAN KANG-CHIH , HSU CHIH-YAO , HUANG KUAN-YING , HSU WEN-WEI , KANG JESSICA , LI HUNG-YUAN 
Published: June 2023

Background: Women with gestational diabetes mellitus (GDM) have excessive fetus growth weeks earlier than the recommended screening period, suggesting that earlier screening and intervention may improve pregnancy outcomes and the health of the offspring. This trial aimed to investigate if early screening and intervention could alter pregnancy outcomes, compared to the standard group.
Methods: We conducted an open-label randomized controlled trial in singleton pregnant women at National Taiwan University Hospital from 2018 to 2021. GDM is diagnosed by 75g 2-hour oral glucose tolerance tests at 18-20 weeks of gestational age for the early-screening group and at 24-28 weeks for the standard-screening group. The diagnostic cutoffs are according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. The primary outcome is a composite measure of pregnancy outcomes, including primary cesarean section, birth weight &gt;90th percentile, neonatal hypoglycemia, cord serum C-peptide &gt;90th percentile, gestational hypertension, preeclampsia and birth trauma.
Results: Total 967 subjects were enrolled, including 483 subjects in the early-screening group and 484 subjects in the standard-screening group. Primary outcome was not statistically different between the two groups (early-screening group, 34.74%; standard-screening group 30.75%, p=0.20). There was also no significant difference in each individual outcome of the primary outcome between two groups except neonatal hypoglycemia, which was significantly higher in the standard-screening group than in the early-screening group (4.14% vs. 1.71%, p=0.0278).
Conclusions: Early screening and intervention of GDM by the one-step method does not improve pregnancy outcomes as compared to standard practice.

Disclosure
C. Kuo: None. S. Lin: None. M. Lin: None. C. Lee: None. C. Chang: None. Y. Chang: None. Y. Tai: None. S. Chen: None. I. Yen: None. K. Fan: None. C. Hsu: None. K. Huang: None. W. Hsu: None. J. Kang: None. H. Li: None.
194-LB: Aggregate Effect of Hemoglobin A1c–Related Genetic Variants on A1c–Glycemia Discordance by Ancestry
Authors: THANGTHAENG NOPPORN , FACIBENE MARIELLA N. , KARTIK SAADHVI , MANDLA RAVI , SCHROEDER PHILIP H. , NORGIL NARA R. , MERCADER JOSEP M. , LEONG AARON 
Published: June 2023

Introduction: The aggregate effect of genetic variants reported to lower A1c independently of glycemia by ancestry remains unclear.
Methods: We recalled 177 patients from the Mass General Brigham biobank with genetic data, enriching recruitment for carriers of the African G6PD variant (rs1050828), α thalassemia 3.7kb deletion, and people in the tails of a European polygenic score (PS) composed of variants associated with A1c but not glucose in GWAS. Subjects underwent 14 days of continuous glucose monitoring (CGM). We defined genetic ancestry using principal component analysis, and calculated A1c-glycemia discordance (measured A1c minus estimated A1c by CGM; ADAG study equation).
Results: Measured A1c and mean glucose were correlated in all groups (r2&gt;0.9). Mean A1c-glycemia discordance was 0.4%-unit higher in African vs. European ancestry. In African ancestry, discordance was 0.5%-unit lower in carriers of the G6PD T allele vs. noncarriers. The bottom decile of PS had 0.3%-unit lower discordance vs. top decile (Figure; p&lt;0.01; all comparisons). Discordance was similar regardless of α thalassemia deletion.
Conclusions: While A1c is an excellent proxy for glycemia in all groups, the A1c-glucose relationship differed by genotype and ancestry. Genetic variation should be considered to promote care equity in diverse populations and avoid misestimating glycemia when using A1c in clinical practice.

Disclosure
N. Thangthaeng: None. M. N. Facibene: None. S. Kartik: None. R. Mandla: None. P. H. Schroeder: None. N. R. Norgil: None. J. M. Mercader: None. A. Leong: Other Relationship; Merck & Co., Inc.

Funding
Doris Duke Charitable Foundation (2020096)
202-OR: Automated Cluster Analysis by Machine Learning Reveals Important Dissimilarities in the Immune Phenotype of T1D, MS, and SLE
Authors: PRIETL BARBARA , ANTONIO VERA-RAMOS JOSÉ , PFEIFER VERENA , KHALIL MICHAEL , HERBSTHOFER LAURIN , SOURIJ HARALD , PIEBER THOMAS 
Published: June 2023

Background: Dysfunction of the immune cell control and break-down of self-tolerance are important in chronic conditions such as type 1 diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Investigating common patterns and dissimilarities between these diseases can help identifying new therapeutic intervention strategies for T1D.
Methods: Unsupervised, automated gating and machine learning (ML) was used to identify clusters of immune cell phenotypes in fluorochrome stained PBMCs from patients with T1D (n=70), RA (n=70), SLE (n=50), MS (n=60) and healthy controls (n=70). The pipeline includes unsupervised pre-gating, FlowSOM clustering, and a statistical analysis (MANOVA) to check for significant differential abundances of cell populations among the conditions.
Results: The unsupervised analysis revealed important differences in the immune cell phenotype of peripheral CD4posT cells between the different auto-immune conditions. IL7alpha receptor (CD127) positive T cell clusters, such as CD3hiCD4hiCD15sposCD127hiCD161med cells are significantly decreased in T1D (p&lt;0.001) compared to MS. Clusters of IL7Rpos memory T cells, expressing the co-stimulatory CD28 molecule are significantly increased in T1D (p&lt;0.001) and SLE (p&lt;0.001) compared to MS. Clusters including Treg-like phenotypes are significantly decreased in MS (p&lt;0.001) compared to T1D, SLE and RA.
Discussion: IL-7R (CD127) and its gene polymorphism plays a major role in MS and mediates homeostatic proliferation in T1D. In SLE serum sIL-7R is associated with disease activity. Using unsupervised machine learning we were able to identify interesting clusters of immune cells expressing CD127 that show significantly different abundancies. Learning from immune modifying therapies used in MS and SLE treatment could help to develop new strategies for future T1D (combinational)-therapies targeting IL7/IL7R complexes.

Disclosure
B.Prietl: None. J.Vera-ramos: None. V.Pfeifer: None. M.Khalil: Advisory Panel; Novartis, Biogen, Gilead Sciences, Inc., Merck & Co., Inc., Research Support; Novartis, Biogen, Roche Pharmaceuticals. L.Herbsthofer: None. H.Sourij: Advisory Panel; Amgen Inc., Amryt Pharma Plc, Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Boehringer Ingelheim Inc., Novo Nordisk A/S, Bayer Inc., Sanofi. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics.

Funding
JDRF/Lupus Research Alliance/National MS Society Joint RFA (2-SRA-2021-1043-S-B)
204-OR: An Early Immune Signature in Prediabetes Can Predict Progression to Type 2 Diabetes
Authors: BAIG SONIA , NI AUNG NWE , YI LEON HWANG YOU , TAN CRYSTAL , LEE MICHELLE H. , SHU QIN OOI DELICIA , SHABEER MUHAMMED , MAGKOS FAIDON , NIKOLAJCZYK BARBARA , GINHOUX FLORENT , TOH SUE-ANNE 
Published: June 2023

Inflammation promotes conversion from metabolically healthy to type 2 diabetes (T2D) in animal models, but convincing demonstrations of this relationship have not been reported in people. We aimed at identifying the cellular and cytokine profile of immune cells, as major sources of inflammation, during progression to T2D. We studied subjects who did or did not convert to T2D in a longitudinal observational cohort study (APT-2D), where drug naïve individuals without T2D at baseline (with normoglycemia or prediabetes) are monitored for disease progression by assessing metabolic function every 6 months for 3 years or until conversion to T2D. Immune cell composition in peripheral blood was studied at baseline and at the point of T2D diagnosis. Correlation analysis was conducted between changes in cell frequency and metabolic parameters: Glycated hemoglobin (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR); fasting insulin (FI); insulin-mediated glucose disposal (M/I); and acute insulin response (AIR). Thirty-two converters aged 49.5 ± 1.6 years with BMI 28.8 ± 0.8 kg/m2 were studied, along with sixty-four non-converters matched for age, gender, and ethnicity. At baseline, our results revealed lower frequencies of classical monocytes and type 2 conventional dendritic cells among converters compared to non-converters, which correlated negatively with HbA1c, HOMA-IR and FI and positively with AIR. At onset of T2D, frequencies of CD8+ and CD4+ naïve T cells, CD19+ B cells, and basophils increased in converters compared to their pre-conversion state and among them CD4+ naïve T cell and CD19+ B cell frequencies correlated negatively with HOMA-IR and FI. Stimulated PBMCs from converters compared to non-converters at baseline produced lower amounts of cytokines (TNFa, IL17A, IL17F, TGFb, IFNg), which did not change after conversion to T2D. Flow cytometric and cytokine profiling thus indicated that changes in immune cell function in prediabetes is linked to T2D conversion.

Disclosure
S.Baig: None. F.Ginhoux: None. S.Toh: None. N.Aung: None. Y.Hwang: None. C.Tan: None. M.H.Lee: None. D.Ooi: None. M.Shabeer: None. F.Magkos: None. B.Nikolajczyk: None.

Funding
National Medical Research Council of Singapore (MOHIAFCat1/0048/2016)
226-OR: Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes—A Seven-Year Longitudinal Study
Authors: SHAH VIRAL N. , SAKAMOTO CASEY , PYLE LAURA , AKTURK HALIS K. , POLSKY SARIT , FORLENZA GREGORY P. , SNELL-BERGEON JANET K. 
Published: June 2023

Introduction: Continuous glucose monitoring (CGM) metrics such as time in range (TIR; 70-180 mg/dL) and their goals have been proposed as new metrics to assess diabetes management. However, longitudinal studies validating TIR with diabetes complications are lacking.
Methods: We analyzed up to 7 years of retrospective longitudinal CGM data of 90 adults with type 1 diabetes (T1D) without a diagnosis of diabetic retinopathy [DR] (Control group) and 70 adults with new incident diagnosis of DR between June 2018-December 2020 but had normal eye examinations in the past (DR group). Associations between DR and CGM metrics were assessed via linear mixed models adjusting for age and diabetes duration.
Results: Baseline characteristics are provided in Figure 1A. A1c was positively associated with development of DR in adults with T1D (Figure 1B). TIR was negatively associated with development of DR (Figure 1C). Time in tight target range (TTIR 70-140 mg/dL) and time above range (TAR&gt;180 mg/dL) were also associated with DR (p&lt;0.001).
Conclusion: CGM metrics such as TIR, TTIR and TAR were associated with development of incidental DR in adults with T1D. To our knowledge, this is the first longitudinal study to demonstrate association between CGM metrics and DR.

Disclosure
V.N.Shah: Advisory Panel; LifeScan Diabetes Institute, Medscape, Consultant; DKSH, Research Support; Novo Nordisk, Tandem Diabetes Care, Inc., Dexcom, Inc., Insulet Corporation, JDRF, National Institutes of Health, Speaker's Bureau; Dexcom, Inc., Insulet Corporation. C.Sakamoto: None. L.Pyle: 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. S.Polsky: Other Relationship; diaTribe, Research Support; Dexcom, Inc., Medtronic, Hemsley Charitable Trust, JDRF, NIH - National Institutes of Health. G.P.Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. J.K.Snell-bergeon: None.

Funding
JDRF (2-SRA-2021-1069-S-B)
231-OR: Reduced NKX2-2 Expression Enhances Insulin Secretion by Primary Human ß-Cells
Authors: PETTWAY YASMINYE D. , WALKER JOHN , DAI CHUNHUA , ARAMANDLA RADHIKA , HOPKIRK ALEXANDER L. , REIHSMANN CONRAD , DAVIS COREY , JENKINS REGINA , SUSSEL LORI , PARKER STEPHEN , POWERS ALVIN C. , BRISSOVA MARCELA 
Published: June 2023

Pancreatic islet endocrine cell phenotype and function are tightly regulated by transcription factor (TF) regulatory networks. In a mouse model of pancreas organogenesis, the key islet-enriched TF NKX2.2 governs both β and α cell specification. Further, loss of NKX2.2 in adult mouse β cells results in glucose intolerance, reduced insulin content, and polyhormonal β cells, demonstrating its importance in the maintenance of β cell phenotype. To understand the undefined role of NKX2.2 in adult human islets, we utilized adenoviral delivery of CRISPR and shRNA constructs in our primary human pseudoislet system to knockout (gNKX2-2) or knockdown (shNKX2-2) NKX2-2 in islet cells, respectively (n=4-6 donors without diabetes). Immunofluorescence analyses of gNKX2-2 pseudoislets demonstrated loss of NKX2.2 signal across β (81 ± 2.0%; p&lt;0.001), α (58 ± 5.5%; p=0.001), and δ cells (83 ± 2.2%; p&lt;0.001) compared to scrambled controls (gSCR). Surprisingly, functional assessment by dynamic perifusion revealed increased insulin secretion in gNKX2-2 versus gSCR pseudoislets measured as area under the curve in response to 16.7 mM glucose (6.64 ± 1.53 vs. 3.55 ± 1.53 ng/100 islet equivalents (IEQs); p=0.007) and cAMP-evoked potentiation with 16.7 mM glucose + 100 μM isobutylmethylxanthine (IBMX) (5.43 ± 0.50 vs. 3.15 ± 0.59 ng/100 IEQs p=0.003) without changes in total insulin content (gNKX2-2 vs. gSCR: 3.64 ± 0.75 vs. 4.78 ± 0.87 ng/IEQ, p=0.45). Furthermore, these findings were recapitulated in shNKX2-2 versus shSCR human pseudoislets (16.7 mM glucose: 10.17 ± 2.46 vs. 6.50 ± 2.51 ng/100 IEQs, p=0.02; 16.7 mM glucose + IBMX: 8.43 ± 1.31 vs. 4.21 ± 1.33 ng/100 IEQs, p=0.0002; insulin content: 6.18 ± 1.05 vs. 7.53 ± 1.26 ng/IEQ, p=0.36), where we observed a reduction in NKX2.2hi β (65 ± 10%; p=0.008), α (52 ± 5.5%; p=0.003), and δ cells (83 ± 4.6%; p=0.003). Collectively, our data indicate a critical role of NKX2-2 in the maintenance of primary adult human β cell function and suggest differential roles in islet function across species.

Disclosure
Y.D.Pettway: None. S.Parker: Research Support; Pfizer Inc. A.C.Powers: None. M.Brissova: None. J.Walker: None. C.Dai: None. R.Aramandla: None. A.L.Hopkirk: None. C.Reihsmann: None. C.Davis: None. R.Jenkins: None. L.Sussel: None.
234-OR: Succinate Potentiates Insulin Secretion through SUCNR1
Authors: SABADELL-BASALLOTE JOAN , ASTIARRAGA BRENNO D. , EJARQUE MIRIAM , REPOLLÉS-DE-DALMAU MARIA , SUREDA FRANCESC X. , DE JESUS DARIO F. , NÚÑEZ ROA CATALINA , MARI ANDREA , KULKARNI ROHIT , VENDRELL JOAN J. , FERNANDEZ-VELEDO SONIA 
Published: June 2023

Here, we examined the role of succinate, a metabolite that acts by engaging the succinate receptor 1 (SUCNR1), in regulating insulin secretion by β-cells. We found that glucose increases SUCNR1 expression in β-cells and that activating SUCNR1 with either extracellular succinate or a synthetic agonist boosts glucose-stimulated insulin secretion through the Gq and PKC signaling pathways. Also, we identified that SUCNR1 is essential for preserving insulin secretion in a diet-induced insulin-resistance model. Mice with β-cell-specific SUCNR1 deficiency had impaired glucose tolerance and reduced insulin secretion when fed a high-fat diet, without changes in β-cell mass or insulin sensitivity. To investigate the physiological significance of succinate as a secretagogue in humans, we studied the potential connection between circulating succinate levels and β-cell function in response to oral and intravenous glucose challenges in a cohort of patients with impaired glucose tolerance (IGT). These patients were characterized by presenting hyperinsulinemia during both oral and intravenous glucose tests, compared to normal glucose tolerance (NGT) individuals. Moreover, succinate levels were elevated in IGT patients in response to these challenges compared to NGT patients, whereas circulating GLP-1 levels during the tests were not different between groups. Remarkably, we found that circulating succinate levels are positively correlated with insulin secretion potentiation during intravenous glucose administration, indicating that this system is activated by high glucose levels and partially regulated by the β-cell in an autocrine fashion. These findings suggest that succinate may act as a hormone, potentiating insulin secretion in humans through SUCNR1- a compensatory mechanism particularly relevant in the hyperinsulinemia elicited by insulin resistance. Our work sheds new light on the role of the succinate-SUCNR1 axis as a potential therapeutic target for improving insulin secretion in metabolic disorders.

Disclosure
J.Sabadell-basallote: None. J.J.Vendrell: None. S.Fernandez-veledo: None. B.D.Astiarraga: None. M.Ejarque: None. M.Repollés-de-dalmau: None. F.X.Sureda: None. D.F.De jesus: None. C.Núñez roa: None. A.Mari: Consultant; Eli Lilly and Company. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago.

Funding
Spanish Ministry of Science and Innovation (SAF2015-65019-R, RTI2018-093919-B-100); Instituto de Salud Carlos III (FI18/00151, CP10/00438, CPII16/00008); Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CB07708/0012); Catalan Association of Diabetes (PV21039S)
249-LB: CRISPR/Cas9-Mediated Deletion of FGF Receptor 1 in AgRP Neurons Results in Obesity and Impaired Glucose Metabolism
Authors: SHOOKSTER DANIEL , HUANG HU 
Published: June 2023

Obesity remains a growing epidemic as current treatment approaches have limited success. We have recently identified hypothalamic α-Klotho as a novel metabolic regulator; however, the downstream pathways remain unclear. Using a Cre-dependent CRISPR/Cas9 system alongside transgenic mice to investigate the role of FGFR1 in defined neuron populations of adult mice, we show that deletion of FGFR1 in AgRP neurons results in increased weight gain and adiposity, worsened glucose tolerance, and increased liver lipid accumulation. Mechanistically, deletion of FGFR1 negates pERK signaling and the ability of α-Klotho to reduce fasting-induced AgRP neuron activity in mice. While in hypothalamic cells, knockdown of FGFR1 prevents FOXO1 phosphorylation by α-Klotho, providing evidence of an α-Klotho-FGFR1-PI3K-FOXO1 signaling axis in AgRP neurons. Taken together, our data demonstrate the metabolic role of FGFR1 in AgRP neurons and identify it as a critical regulator of energy and glucose homeostasis.

Disclosure
D. Shookster: None. H. Huang: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK121215 to H.H.)
25-LB: Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy
Authors: GONZALEZ VICTOR H. , BRIGELL MITCHELL G. , SU DANIEL , PATEL RONIL , WITHERS BARBARA , KELLEY MARK , HADDAD LOUIS , SOOCH MINA , PEPOSE JAY S. , KAISER PETER K. , BOYER DAVID S. 
Published: June 2023

APX3330 is an oral, novel, small-molecule inhibitor of Ref-1, in diabetic retinopathy (DR) patients. ZETA-1 was a multi-center, placebo-controlled, double-masked Phase 2 trial. Subjects were randomized 1:1 to receive APX3330 (total 600 mg/day) or placebo BID for 24 weeks. Eligible subjects had non-proliferative DR (NPDR) or mild proliferative DR, corresponding to DR severity scale (DRSS) scores of 47, 53, or 61 as confirmed by the Duke reading center. The primary efficacy endpoint was the % of subjects with ≥ 2-step DRSS improvement in the study eye at week 24 compared to baseline. Several key pre-specified endpoints were evaluated.
Results: ZETA-1 trial enrolled 103 DR subjects with 90% having NPDR with a baseline DRSS of 47 or 53. The primary endpoint was not met with 8% of study eyes showing ≥ 2-step DRSS improvement in each treatment group. Consistent with its mechanism of action of bringing VEGF and inflammation to physiologic levels, APX3330 demonstrated a statistically significant reduction in binocular ≥ 3-step worsening after 24 weeks, with 16% of placebo subjects worsening compared to 0% of APX3330 subjects (p=0.04). 19% of placebo subjects lost ≥5 BCVA letters compared to 5% of APX3330 subjects (p=0.07). AEs that occurred in ≥5% of subjects were pruritis, rash, and worsening of DR or DME in the placebo group. No subjects withdrew due to rash or pruritis.

Disclosure
V. H. Gonzalez: Consultant; Alimera, Bausch + Lomb, Research Support; Adverum Biotechnologies, AbbVie Inc., Apellis, Genentech, Inc., IQVIA Inc., Iveric Bio, Regeneron. P. K. Kaiser: Consultant; Ocuphire, AbbVie Inc., Bausch + Lomb, Bayer Inc., Regeneron, Ocular Therapeutix, Novartis, REGENXBIO Inc. D. S. Boyer: Advisory Panel; 3Boehringer Ingelheim Canada Ltd. /Ltée, AbbVie Inc., Adverum Biotechnologies, Alexion Pharmaceuticals, Inc., Alkahest, Allergan, Amgen Inc., Apellis, Bausch + Lomb, Chengdu Pharmaceuticals, F. Hoffmann-La Roche Limited, Genentech, Inc., Iveric Bio, Gyroscope, Janssen Pharmaceuticals, Inc., Kodiak Pharmaceuticals, NGM Biopharmaceuticals, Oxurion, Novartis, ocuphire, Roche Pharmaceuticals, REGENXBIO Inc., Other Relationship; 4D Pharma PLC. M. G. Brigell: Consultant; Ocuphire Pharma, ONL Therapeutics. D. Su: None. R. Patel: Employee; Ocuphire Pharma. B. Withers: Employee; Ocuphire. M. Kelley: None. L. Haddad: None. M. Sooch: Board Member; Ocuphire Pharma, Employee; Ocuphire Pharma, Stock/Shareholder; Ocuphire Pharma. J. S. Pepose: Consultant; Acufocus, Bausch + Lomb, Brim Biotechnology, Johnson & Johnson Medical Devices Companies, Kala Pharmaceuticals, Mimetogen, Ocuphire Pharma, OKYO Pharma, Stuart Therapeutics, Thea Pharma.
254-LB: In Vivo Mapping of Postprandial Hepatic Glucose Metabolism Using Stable Isotope-Assisted Metabolic Imaging in Roux-en-Y Gastric Bypass Adults and Nonoperated Controls
Authors: LANGE NAOMI F. , POLI SIMONE , HERZIG DAVID , SCHIAVON MICHELE , DALLA MAN CHIARA , KREIS ROLAND , BALLY LIA 
Published: June 2023

We aimed to assess the impact of Roux-en-Y gastric bypass (RYGB) on hepatic glucose (glc) kinetics using stable isotope-assisted magnetic resonance spectroscopy (MRS). Ten post-RYGB adults (2M, age=39.2±3.1 y, BMI=28±1 kg/m2; mean±SE) and ten non-operated adults (HC; 5M, age=36.4±3.2 y, BMI=26±1 kg/m2) underwent metabolic imaging in a 7T (Terra, Siemens) scanner with a triple-tuned surface coil over the liver. Scanning was performed before (T0) and up to 150 min (T150) after oral intake of 60g of deuterated [6,6′-2H2]-Glc using interleaved sequences of 2H2-MRS imaging (hepatic 2H2-glc signal) and 13C-MRS (glycogen). Blood samples were collected for profiling of plasma glc, glc enrichment, insulin and glucagon. General Additive Mixed Models were used for comparative analyses. We observed distinct postprandial profiles of hepatic glc signal (Fig 1). RYGB subjects showed earlier and higher glc peaks, which were mirrored by hepatic glc signal in both groups. Insulin peak levels were higher and glc nadir lower in RYGB. Postprandial endogenous glc was higher in RYGB, which was paralleled by a fall in hepatic glc. In HC, hepatic glc remained elevated until the end of the experiment. Non-invasive stable isotope-assisted MRS imaging has the potential to unravel changes in postprandial hepatic metabolism induced by RYGB and other treatments.

Disclosure
N. F. Lange: None. S. Poli: None. D. Herzig: None. M. Schiavon: None. C. Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. R. Kreis: None. L. Bally: Research Support; Dexcom, Inc., Ypsomed AG.

Funding
Swiss National Science Foundation (PCEGP3_186978)