bluuebunny/crossref_metadata_2025_split huggingface dataset:
273-OR: Postprandial Dysfunction in Metabolic Associated Fatty Liver Disease (MAFLD)
Authors: GRANDT JOSEPHINE , JENSEN ANNE-SOFIE H. , WERGE MIKKEL P. , RASHU ELIAS B. , JUNKER ANDERS , HOBOLTH LISE , MORTENSEN CHRISTIAN , VYBERG MOGENS , SERIZAWA REZA , MØLLER SØREN , GLUUD LISE , WEWER ALBRECHTSEN NICOLAI J. 
Published: May 2022

Metabolic dysfunction in patients with metabolic fatty liver disease (MAFLD) may increase the risk for diabetes development. The liver is essential for the postprandial control of our metabolism and hormonal response, yet most studies focus on fasting conditions. We therefore studied the fasting and postprandial phase in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD, (n = 9, mean age 50 y, mean BMI 35 kg/m2, no/mild fibrosis) , cirrhosis (n = 10, age 62 y, BMI 32 kg/m2, CHILD A/B) and healthy controls (n = 10, age 23, BMI 25 kg/m2) , randomized 1:1 to fasting or Nutridrink (Nutricia, 300 kcal) . None of the postprandial patients had type 2 diabetes (T2D) . In the NAFLD/cirrhosis groups, 17/classified as MAFLD. Peripheral blood samples were collected at 0, 15, 45, 60, 90 and 120 minutes. At time point 60, a transjugular liver biopsy and liver vein blood were taken. Levels of glucose, insulin, C-peptide, glucagon, and fibroblast growth factor 21 (FGF21) were measured in peripheral blood, glucagon and FGF21 also in liver vein blood. Postprandial peak glucose and C-peptide was increased in NAFLD and cirrhosis compared with healthy (mean peak glucose (mM) 7, 10, 6; mean peak C-peptide (pM) 2675, 3340, 1689, respectively) . The postprandial incremental AUC for insulin was significantly increased in patients with NAFLD compared to healthy. Patients with NAFLD and cirrhosis had hyperglucagonemia, a phenotype related to prediabetes. FGF21 was increased in NAFLD and cirrhosis and correlated to age (r= .61, P = .001) and fasting glucose (r = .54, P = .006) . Glucagon levels were higher in liver vein compared to peripheral blood, while FGF21 levels were similar in both compartments.
In summary, patients with NAFLD and cirrhosis without T2D showed significant metabolic dysfunction after a standardized meal compared to healthy controls. We found impaired glucose tolerance, hyperinsulinemia and hyperglucagonemia in both NAFLD and cirrhosis, suggesting a condition of prediabetes in patients with MAFLD.

Disclosure
J. Grandt: None. A.H. Jensen: None. M.P. Werge: None. E.B. Rashu: None. A. Junker: None. L. Hobolth: None. C. Mortensen: None. M. Vyberg: None. R. Serizawa: Consultant; Merck Sharp & Dohme Corp. L. Gluud: Advisory Panel; Novo Nordisk. Consultant; Pfizer Inc. Research Support; Alexion Pharmaceuticals, Inc., Gilead Sciences, Inc., Novo Nordisk, Sobi. N.J. Wewer Albrechtsen: Research Support; Mercodia AB, Novo Nordisk, Regeneron Pharmaceuticals Inc. Speaker's Bureau; Merck & Co., Inc., Mercodia AB.

Funding
Nicolai J. Wewer Albrechtsen was financed by NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude.
274-OR: The Malic Enzyme-1 Links Pyruvate Carboxylase–Mediated Anaplerosis to Redox State in Liver
Authors: INIGO MELISSA MAE R. , FLETCHER JUSTIN A. , KUCEJOVA BLANKA , SHARMA GAURAV , DEJA STANISLAW , FU XIAORONG , BURGESS SHAWN C. 
Published: May 2022

Redox balance is critical for numerous cellular functions, including substrate oxidation, biosynthesis, and antioxidant defenses. Redox homeostasis is dysregulated in many metabolic diseases, including obesity and Type 2 diabetes. In addition to its role in replenishing TCA cycle intermediates, we previously showed that pyruvate carboxylase (PC) -mediated anaplerosis is necessary to regulate redox state, including the NADPH/NADP+ ratio and antioxidant capacity in liver, though the mechanism is unclear. We hypothesized that PC elicits effects on redox by modifying ratios of metabolites involved in redox mediated exchange reactions. Malic enzyme-1 (Me1) catalyzes the reversible, NADPH dependent, decarboxylation of malate to pyruvate. This enzyme plays a vital role in recycling malate and providing NADPH during lipogenesis. We show here that Me1 mediates redox by sensing TCA cycle function through the mass action of malate and pyruvate. We tested the role of Me1, as a sensor of anaplerosis in the TCA cycle and regulator of redox, using acute Me1 knockdown (Me1KD) in liver-specific PC knockout (LPCKO) mice. Stable isotope tracers were used to examine anaplerosis, gluconeogenesis, and pyruvate cycling fluxes, and targeted metabolomics were used to evaluate tissue energy status and redox. Anaplerosis, pyruvate cycling, and gluconeogenesis were lower in the absence of liver PC but were unaffected by Me1KD. Loss of PC decreased the malate/pyruvate ratio, congruent with impaired conversion of pyruvate to TCA cycle intermediates, which resulted in a concomitant decrease in the NADPH/NADP+ ratio. Acute removal of Me1 in LPCKO mice normalized NADPH/NADP+ and restored the malate/pyruvate ratio. Additionally, mitochondrial NAD+/NADH and FAD+/FADH redox states were more oxidized in LPCKO liver and were normalized by loss of Me1. Thus, despite not altering the aforementioned fluxes, Me1 transmits redox state in response to TCA cycle function by sensing alterations in the malate/pyruvate ratio.

Disclosure
M.R.Inigo: None. J.A.Fletcher: None. B.Kucejova: None. G.Sharma: None. S.Deja: None. X.Fu: None. S.C.Burgess: n/a.

Funding
Robert A. Welch Foundation Grant (I-1804)
275-OR: Inhibition of Hepatic ACC Decreases Ketogenesis during Fasting due to Elevated Amino Acid Availability
Authors: DEJA STANISLAW , FLETCHER JUSTIN A. , KUCEJOVA BLANKA , MIZERSKA MONIKA N. , FU XIAORONG , KIM CHAI-WAN , BROWNING JEFFREY , YOUNG JAMEY , HORTON JAY D. , BURGESS SHAWN C. 
Published: May 2022

Activation of fatty acid oxidation is a promising therapy for NAFLD. Lowering acetyl-CoA carboxylase (ACC) activity depletes malonyl-CoA, activates CPT1, and increases mitochondrial fatty acid delivery. ACC1/2 liver double KO mice (LDKO) are protected from hepatic steatosis and have elevated ketogenesis in the prandial state. However, fasted LDKO mice exhibit an unexpected inhibition of ketogenesis, indicated by lower blood ketones and reduced in vivo ketone turnover of [3,4-13C2]acetoacetate and [U-13C4]β-hydroxybutyrate. Despite impaired fasting ketogenesis in vivo, perfused livers isolated from fasted mice and starved primary hepatocytes had normal or elevated ketone production, suggesting that a substrate-mediated mechanism inhibits ketosis in vivo. There were no differences in plasma NEFAs, but hepatic lactate was elevated during fasting in LDKO mice. The increase in lactate was sufficient to suppress ketone production in isolated perfused liver. An in vivo [U-13C3]lactate/pyruvate challenge was more rapidly diluted in fasted LKDO mice, indicating that alternative endogenous sources of pyruvate were available. Indeed, essential amino acids were elevated in fasted LDKO liver, but not plasma, suggestive of hepatic proteolysis as a source of amino acids. Liver size was 20% larger in LDKO mice, independent of glycogen storage or triglyceride content, but was consistent with increased insulin action and activation of Nrf2 which have been linked to hepatomegaly. Autophagy during fasting was normal or increased, suggesting that hepatomegaly supplies excess amino acids in the fasted state. Injection of exogenous alanine or glutamine in fasted WT mice recapitulated the fasted LDKO phenotype by increasing plasma glucose and lactate and decreasing ketone concentrations. Thus, hepatic growth is increased in the absence of malonyl-CoA synthesis, which provides a surplus of amino acids, anaplerotic maintenance of the TCA cycle and lower ketogenesis during fasting.

Disclosure
S.Deja: None. S.C.Burgess: n/a. J.A.Fletcher: None. B.Kucejova: None. M.N.Mizerska: None. X.Fu: None. C.Kim: None. J.Browning: None. J.Young: Consultant; Pfizer Inc., Research Support; Merck & Co., Inc., Stock/Shareholder; Metalytics, Inc. J.D.Horton: Board Member; Draupnir Bio, Consultant; Eli Lilly and Company, ESPERION Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Pfizer Inc., Regeneron Pharmaceuticals Inc.

Funding
National Institutes of Health (R01DK078184, P41EB015908)
280-OR: Updated Diabetes Family Conflict Scale (DFC) Includes Continuous Glucose Monitoring (CGM) Items
Authors: CHEN CHARLOTTE , SHAPIRA AMIT , VOLKENING LISA K. , LAFFEL LORI M. 
Published: May 2022

Introduction: With increased CGM use in youth with T1D, it is timely to assess diabetes-specific family conflict related to CGM use. We aimed to evaluate the psychometric properties of an updated DFC measure that includes CGM items.
Methods: Youth with T1D and their parents completed youth and parent versions, respectively, of the DFC that included 6 CGM-specific items (e.g., responding to CGM alarms) . Higher scores indicate more conflict. Item-to-total correlations and Cronbach’s α assessed internal consistency; correlations determined concurrent and predictive validity.
Results: The sample comprised 1youth (51% male) aged 13.2±2.7 years, with T1D duration 6.6±3.5 years. The final survey had 16 items after removal of those with outdated features, low response variability, or low item-to-total correlation. Cronbach’s α was .91 for youth and .81 for parents. Youth and parent scores were highly correlated (r=.48, p&lt;.0001) . Higher DFC scores were associated with younger youth age (youth: r=-.23, p=.02; parent: r=-.27, p=.004) . Higher youth and parent DFC scores were also associated with adverse psychosocial outcomes: more depressive symptoms (youth: r=.38, p&lt;.0001; parent: r=.35, p=.0002) , more diabetes burden (youth: r=.31, p=.0008; parent: r=.44, p&lt;.0001) , more anxiety traits (youth: r=.23, p=.02; parent: r=.45; p&lt;.0001) , lower youth general quality of life (QoL) (youth: r=-.30, p=.002; parent: r=-.45, p&lt;.0001) and lower youth diabetes-specific QoL (youth: r=-.21, p=.02; parent: r=-.44, p&lt;.0001) . Higher youth and parent DFC scores were associated with lower CGM satisfaction (youth: r=-.36, p&lt;.0001; parent: r=-.28, p=.004) and with less CGM use at the time of DFC scale completion (youth: r=-.33, p=.0004; parent: r=-.31, p=.001) and 3 months later (youth: r=-.19, p=.05; parent: r=-.28, p=.003) .
Conclusion: The updated youth and parent DFC scales demonstrate strong psychometric properties and predictive validity and may be useful in clinical and research settings.

Disclosure
C.Chen: None. A.Shapira: None. L.K.Volkening: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc.

Funding
National Institutes of Health (P30DK036836, R01DK089349, T32DK007260)
281-OR: Psychosocial Benefits of Using Control-IQ Technology: Long-Term Outcomes from a Multiethnic Adult Cohort with Type 1 Diabetes
Authors: SINGH HARSIMRAN , ALENCAR GABRIEL , SANCHEZ HAIDEE , MANNING MICHELLE L. , WHITE KIRSTIN N. , WHEATCROFT ALEX , CARMELO KAREN , GRAHAM RISHI , MUELLER LARS , ARONOFFSPENCER ELIAH S. , PINSKER JORDAN E. , HABIF STEPHANIE 
Published: May 2022

There is mounting evidence supporting the benefits of hybrid closed loop systems for type 1 diabetes (T1D) management. However, published studies lack long-term evaluation of these technologies in ethnically diverse patients including patient-reported outcomes (PROs) assessing lived experiences with these devices. As part of the Control-IQ Observational (CLIO) study, we evaluated psychosocial outcomes in T1D adults using the Tandem Diabetes Care t:slim X2 insulin pump with Control-IQ technology. Participants completed PRO measures including open-ended items at baseline (pre) , 3, 6, and 12 months (post) . Wilcox signed rank-test was used to assess differences and qualitative data was analyzed using thematic analysis. In all, 13adult study completers (57.6% female) (White=1084, Hispanic=86, Black=38, Asian=16, Mixed=42) were included in the analysis. Overall, there was a 25.2% improvement in satisfaction with insulin delivery device (IDD) using Control-IQ technology at post (mean=8.83±1.15) vs. pre (i.e., previous IDD) (7.06±2.04) (p&lt;0.001) . The Asian cohort reported greater improvement (33.2%) than others. A significant reduction in diabetes impact (33.6%) was noted overall at post (p&lt;0.001) with Hispanic participants reporting greater reduction in diabetes burden (42.8%) than others. For perceived impact of diabetes on quality of life, there was an overall reduction in diabetes impact at post (p&lt;0.001) with Asians showing greater reduction (26.3%) vs. others, specifically in the “freedom to eat as you wish” aspect of life. At post, 71% reported improved sleep quality using Control-IQ technology. Thematic analysis supported these findings highlighting improved diabetes control, quality of life, and ease of use as valuable experiences supporting long-term use of Control-IQ technology. These data demonstrate substantial and sustained psychosocial improvements using Control-IQ technology in diverse ethnic cohorts with T1D.

Disclosure
H.Singh: Employee; Tandem Diabetes Care, Inc. E.S.Aronoffspencer: Research Support; Tandem Diabetes Care, Inc. J.E.Pinsker: Employee; Tandem Diabetes Care, Inc., Stock/Shareholder; Tandem Diabetes Care, Inc. S.Habif: Employee; Tandem Diabetes Care, Inc. G.Alencar: Employee; Tandem Diabetes Care, Inc. H.Sanchez: Employee; Tandem Diabetes Care, Inc. M.L.Manning: Employee; Tandem Diabetes Care, Inc. K.N.White: Employee; Tandem Diabetes Care, Inc. A.Wheatcroft: Employee; Tandem Diabetes Care, Inc. K.Carmelo: None. R.Graham: Research Support; Tandem Diabetes Care, Inc. L.Mueller: Employee; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Stock/Shareholder; Tandem Diabetes Care, Inc.

Funding
Tandem Diabetes Care
283-OR: Neighborhood Disadvantage for Teens with Type 1 Diabetes (T1D) : Associations with Glycemic and Psychosocial Outcomes
Authors: O'DONNELL MAEVE B. , DURAN BRENDA , ZHOU CHUAN , MALIK FAISAL , PIHOKER CATHERINE , SCOTT SAMANTHA R. , ELLISOR BRITNEY M. , PEREZ SAMANTHA GARCIA , DESALVO DANIEL , HILLIARD MARISA E. , YI-FRAZIER JOYCE 
Published: May 2022

Background: For teens with T1D, stress related to neighborhood disadvantage may exacerbate diabetes distress and contribute to disparities in care and outcomes.
Objective: We explored associations among neighborhood disadvantage and clinical/psychosocial outcomes to identify patterns to inform future stress-resilience interventions.
Methods: At baseline of a 2-site psychosocial intervention trial, 173 teens aged 13-18 years with T1D ≥1 year and elevated diabetes distress (57% Female, 2% American Indian/Alaska Native, 4% Asian, 15% Black, 11% Hispanic White, 6% Hispanic Non-White, 63% Non-Hispanic White, mean A1c= 8.7±2.1, 66% pump use) completed a demographics form and measures of resilience, diabetes distress, diabetes quality of life and family conflict.. We retrieved area deprivation index (ADI) scores for home addresses; this measure of neighborhood disadvantage considers factors related to income, education, employment, and housing quality at the census block group level and provides a state-relative decile score (higher scores indicate more disadvantage) . Fisher’s exact tests and regression analyses were used to examine associations of ADI with A1c and survey data.
Results: Participant ADI spanned all deciles, M = 3.7± 2.4. Hispanic White/Non-White and Black teens and those not using pump had higher mean ADI. Higher ADI was associated with higher A1c (β=.18 [.06, 0.29], p=.003) and higher family conflict (β=.63 [.12, 1.1], p=.015) . ADI was not significantly related to resilience, diabetes distress, or quality of life.
Conclusions: In a diverse sample of distressed teens with T1D, neighborhood disadvantage was associated with Hispanic ethnicity and Black race, lower pump use, poorer glycemic control and greater family conflict. Considering neighborhood disadvantage may help providers deliver personalized care to target systemic sources of stress, ultimately improving clinical and psychosocial outcomes.

Disclosure
M.B.O'donnell: None. M.E.Hilliard: None. J.Yi-frazier: None. B.Duran: None. C.Zhou: None. F.Malik: n/a. C.Pihoker: None. S.R.Scott: None. B.M.Ellisor: None. S.Garcia perez: None. D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation.

Funding
US National Institutes of Health R01DK121224
292-OR: Changes in Glycemia during Exercise Differ for Aerobic, Interval, and Resistance Workouts with No Impact of Insulin Delivery Modality for Adults with Type 1 Diabetes (T1D)
Authors: RIDDELL MICHAEL , PATTON SUSANA R. , MARTIN CORBY K. , LI ZOEY , JACOBS PETER G. , GILLINGHAM MELANIE B. , GAL ROBIN L. , DOYLE FRANCIS J. , CLEMENTS MARK A. , CALHOUN PETER , CASTLE JESSICA R. , BECK ROY , RICKELS MICHAEL R. 
Published: May 2022

Glycemic responses differ by exercise classification (i.e. aerobic, interval, resistance) in individuals with T1D, but the impact of insulin delivery modality (multiple daily injections [MDI], pump, closed loop) on these differences is unclear. Data from the Type 1 Diabetes Exercise Initiative study allowed us to compare glycemic responses by insulin delivery method. Adults (N=497) with T1D ([mean ± SD] age= 37 ± 14 years; HbA1C= 6.6 ± 0.8%) were assigned to complete six at-home sessions of aerobic, interval, or resistance exercise over 4 weeks, using study-developed instructional videos approximately 30 minutes in duration. Mean [95% CI] change in glucose during the assigned exercise was -[95% CI -22, -16], -15 [-18, -12], and -9 [-12, -7] mg/dL for aerobic, interval, and resistance exercise, respectively (P&lt;0.001) , after adjusting for baseline glucose, insulin delivery modality, age, and sex. This pattern was similar irrespective of insulin delivery modality (Figure) .
In summary, regardless of insulin delivery modality, adults with T1D experienced the largest glucose drop for aerobic exercise followed by interval exercise and resistance exercise.

Disclosure
M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Consultant; Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. P.Calhoun: None. J.R.Castle: Advisory Panel; Insulet Corporation, Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Pacific Diabetes Technologies. R.Beck: Consultant; Diasome, Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Research Support; Ascensia Diabetes Care, Beta Bionics, Inc., Bigfoot Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Tandem Diabetes Care, Inc. M.R.Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc. S.R.Patton: None. C.K.Martin: Advisory Panel; Wondr Health, Board Member; EHE Health, Other Relationship; ABGIL, ABGIL, Academy of Nutrition and Dietetics. Z.Li: None. P.G.Jacobs: Other Relationship; Pacific Diabetes Technologies, Research Support; Dexcom, Inc. M.B.Gillingham: None. R.L.Gal: None. F.J.Doyle: Other Relationship; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Stock/Shareholder; Mode AGC. M.A.Clements: Consultant; Glooko, Inc., Research Support; Abbott Diabetes, Dexcom, Inc.
293-OR: Effects on Metabolic Control and Body Composition of Insulin Therapy Optimization in Patients with Cystic Fibrosis–Related Diabetes
Authors: GRANCINI VALERIA , PORCARO LAURA L. , GAGLIO ALESSIA , RESI VERONICA , ORSI EMANUELA 
Published: May 2022

Cystic fibrosis related diabetes (CFRD) occurs in 19% of adolescents and 40-50% of adults with CF. The partial to complete insulin deficiency leads not only to hyperglycaemia, but also to loss of muscle mass and induction of a catabolic state. Therefore, insulin is the only recommended therapy for CFRD. Continuous subcutaneous insulin infusion (CSII) has been associated to improved glycaemic control in CFRD in small studies, if compared to multiple daily injections (MDI) , mostly due to better coverage of dietary requirements of these patients (high calories, not carbohydrate restrictions, several snacks) . The aim of this study is to evaluate the effects of insulin therapy optimization combined to a structured educational program (training to Sensor Augmented Pump -SAP- therapy and carbohydrates counting) on metabolic control and body composition in patients with CFRD requiring insulin therapy. 22 patients agreed to participate in the program and, at the end of it, switched to SAP therapy. 29 patients continued the outpatient checks without joining the program. Patients of both groups were re-evaluated 2 years after baseline. Patients in the educational program group demonstrated a substantial improvement in glycometabolic control (HbA1c 7.4±1.4 vs. 6.5±0.6%; average blood glucose 8.5±1.6 vs. 7.4±1.1 mmol/L; Glucose management indicator - GMI 7.2±0.9 vs. 6.5±0.5%; time in range - TIR 64.2±18.0 vs. 80.38±10.1%; time above range - TAR 31.0±18.8 vs. 16.2±9.1%; time below range - TBR 4.76±3.5 vs. 3.0±2.0%, P&lt;0.05) and in body composition, assessed with bioimpedance (fat free mass - FFM 78.9±8.6 vs. 85.1±7.0%, total body water - TBW 57.9±6.3 vs. 63.2±6.7 L, P&lt;0.05) . The same parameters didn’t differ from basal to final evaluation in the control group.
In conclusion, a structured program resulting in therapy optimization leads to a significative improvement in glycometabolic control and, consequently, in body composition, due to insulin’s anabolic effect

Disclosure
V.Grancini: None. L.L.Porcaro: None. A.Gaglio: None. V.Resi: None. E.Orsi: None.