bluuebunny/crossref_metadata_2025_split huggingface dataset:
157-LB: A Randomized Trial of Continuous Glucose Monitoring upon Emergency Department Discharge
Authors: O'CONNOR MARK J. , DING XINYI , HERNANDEZ CAMILA , HUBACZ LISA M. , CHURCH RICHARD J. , O'CONNOR LAUREL 
Published: June 2023

Background: People with type 2 diabetes (T2D), particularly those with limited access to longitudinal care, frequently present to the emergency department (ED), leading to increased hospital utilization and disjointed care. Continuous glucose monitoring (CGM) has been shown to improve patient engagement and glycemic outcomes in outpatients, so we hypothesized that it would be beneficial if initiated upon ED discharge.
Methods: We randomized adults with T2D who were seen in the ED for hypo- or hyperglycemia to either flash CGM or care coordination alone. All participants were scheduled to follow up in our diabetes specialty clinic within two or three weeks. Outcomes included clinic attendance, patient-reported diabetes-related distress, satisfaction with CGM, and follow-up hemoglobin A1c.
Results: We recruited 30 participants, including 13 with newly diagnosed T2D. We found no significant difference between the CGM (n=16) and control (n=14) groups in terms of clinic attendance (75 versus 64%, P=0.69) or the change in diabetes-related distress as measured via the Diabetes Distress Scale. Among participants in the CGM group who returned for follow up, 83% found CGM helpful, as did 90% of their providers. The mean A1c reduction after approximately 3 months was greater in the CGM group (5.2 versus 1.9%, P=0.051), although the groups were not balanced in terms of diabetes duration. Among participants with newly diagnosed T2D, excluding those missing data, five out of five in the CGM group had a follow-up A1c under 7% (from a mean baseline of 12.9%) compared to zero out of two in the control group (P=0.048).
Discussion: Our study demonstrates the feasibility of starting CGM in the ED, an important setting for engaging difficult-to-reach patients. We did not see an effect of CGM on follow-up clinic attendance or diabetes-related distress, but there was a trend towards improved A1c at 3 months in the CGM group. Our study was limited by its small sample size, however, as recruitment in the ED can be challenging.

Disclosure
M. J. O'connor: None. X. Ding: None. C. Hernandez: None. L. M. Hubacz: None. R. J. Church: None. L. O'connor: None.

Funding
Herman G. Berkman Diabetes Clinical Innovation Fund
1581-P: Systemic Alteration of Amino Acids Metabolism in Glutamate Dehydrogenase Gain-of-Function Mutation Knockin Mice
Authors: SU CHANG , HAN DONGNA , MENG SHI , ZHU QIUSHA , ZHOU XUE , JIANG HAOWEN , LI JIA , GONG CHUNXIU , LI CHANGHONG 
Published: June 2023

Patients with gain-of-function (GoF) mutations of glutamate dehydrogenase (GDH) have protein-sensitive hypoglycemia, hyperammonemia, epilepsy, and intellectual disability (HI/HA syndrome). Studies of mouse models with a beta-cell specific expression of H454Y hGDH suggest that the mechanisms of HI are caused by increased glutaminolysis induced by GDH GoF in islets. However, the mechanism of hyperammonemia is still unknown. In order to study the systemic effects of GDH GoF, H454Y GDH knockin mice (H454Y-GDH-KI) were created. Enzyme kinetic of GDH in the brain, kidney and liver confirmed that H454Y was successfully expressed with impaired GTP inhibition. H454Y-GDH-KI mice have a ~2.5-fold elevation of plasma ammonia and fasting hypoglycemia, similar to HI/HA patients. Tissues (brain, liver and kidney) and plasma amino acids profiles were determined by LC-MS. Compared to wildtype, the amino acids profile in the kidney was unaltered in KI mice. In contrast, KI liver had 60% lower glutamine, unchanged glutamate and aspartate, increased branch chain amino acids, etc. The glutamine of KI brain was 40% lower than the wildtype, glutamate and GABA was unchanged. Interestingly, plasma glutamine in KI mice was 30% higher compared to controls. A similar phenomenon has also been observed in HI/HA patients. We hypothesize that hyperammonemia is mainly caused by the increased glutaminolysis in KI liver. Higher plasma glutamine can be explained by the increased activity of tissue glutamine synthetase (GS). GS and glutamine serve as an ammonia sink, which is the main mechanism for the removal of increased ammonia in KI mice. We therefore applied the GS inhibitor, methionine sulfoximine (MSO) to KI mice. MSO significantly increased ammonia levels in KI mice after a single dose of injection. These studies in H454Y-GDH-KI mice suggest that GDH GoF in the liver is the main cause of hyperammonemia. GS plays an important role in ammonia removal.

Disclosure
C.Su: None. D.Han: Employee; Nanjing AscendRare Pharmaceutical Technology. S.Meng: Employee; Nanjing AscendRare Pharmaceutical Technology. Q.Zhu: Employee; Nanjing AscendRare Pharmaceutical Technology. X.Zhou: Employee; Nanjing AscendRare Pharmaceutical Technology. H.Jiang: None. J.Li: None. C.Gong: None. C.Li: Employee; Hua Medicine, Nanjing AscendRare Pharmaceutical Technology.

Funding
Beijing Natural Science Foundation (L212037)
1586-P: Post-OGTT Low Blood Glucose in Individuals with Metabolic Syndrome, Metabolic Phenotypes, and Metabolic-Associated Fatty Liver Disease
Authors: GIGNAC THEO , MORISSETTE ARIANNE , AGRINIER ANNE-LAURE , GAGNON CLAUDIA , VOHL MARIE-CLAUDE , MARETTE ANDRE , CARREAU ANNE-MARIE 
Published: June 2023

Introduction: Post-prandial low blood glucose (LBG) is usually associated with late postprandial hyperinsulinemia in metabolic syndrome (MetS), but have not been well studied.
Objectives: We aimed to 1) characterize insulin/glucose metabolism associated with LBG post 75g OGTT in a sample of individuals with MetS; and 2) assess the association between MAFLD (≥ 5% liver fat at MRI) and LBG.
Methods: Plasma glucose, insulin and c-peptide concentrations were measured on OGTT over 180 mins. Insulin sensitivity and secretion were assessed with the Oral Minimal Model. During OGTT, we defined glucose ≤ 50 mg/dl as LBG, glucose &gt; 70 mg/dl as no LBG and glucose 51-70 mg/dl as undefined status and were excluded from this analysis.
Results: Of 82 participants, 50 were included and 15 (18 %) experienced LBG. Of the 33 participants who underwent MRI, 48% had MAFLD. Median age and BMI were 59 [IQR: 49-74] years and 28 [IQR: 26-31] kg/m2 respectively. Women represented 70% (n=35) of participants and experienced less LBG (p=0.0002) than men. Individuals experiencing LBG had higher insulin sensitivity (p=0.02), higher ß cell function (p=0.03), earlier glucose peaks (p&lt;0.0001) and lower c-peptide peaks (p=0.007) than those without LBG. MAFLD was not associated with more LBG (p=0.7), but was associated with a different insulin curve. LBG+MAFLD status was associated with higher and later c-peptide and insulin levels compared to LBG without MAFLD status.
Conclusion: In contrary to our hypothesis, individuals with MetS without MAFLD experiencing glucose ≤ 50 mg/dl during OGTT displayed a healthier metabolic profile. However, individuals with MAFLD experiencing a LBG during OGTT had a glucose phenotype similar to the late post-prandial hyperinsulinemic hypoglycemia often found in prediabetes state and associated with worst metabolic parameters. This suggests that MAFLD may be an important feature of MetS associated with a different post-OGTT glucose metabolism.

Disclosure
T.Gignac: None. A.Morissette: None. A.Agrinier: None. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. M.Vohl: None. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. A.Carreau: Advisory Panel; Novartis, Consultant; Valbiotis, Speaker's Bureau; Novo Nordisk Canada Inc.
1587-P: The NADPH Oxidase 4 Regulates Anti-inflammatory Signals to Modulate Lipid Depot Distribution between Adipose Tissue and Liver
Authors: SZANTO ILDIKO 
Published: June 2023

Excessive white adipose tissue (WAT) expansion and lipid load is associated with the onset of insulin resistance and Type 2 diabetes. In addition, lipid storage may “overflow” into the liver triggering the apparition of nonalcoholic fatty liver disease (NAFLD). Two major components linking white adipose tissue (WAT) dysfunction and NAFLD to insulin resistance are the deregulation of cellular redox homeostasis and the onset of chronic, low-grade inflammation. NADPH oxidases (NOX-es) produce oxidant molecules that control redox homeostasis and cytokine signaling in inflammatory cells. In particular, NOX4 is essential for the signal transduction of the transcription factor, Stat6 that mediates anti-inflammatory actions of IL-4 and IL-13. In order to elucidate the in vivo interaction between NOX4 and Stat6 and to assess their relevance in the onset of “obese” WAT and NAFLD, we created mice with double knock-out for NOX4 and Stat6 (DKO) and compared their metabolic phenotype to littermates with single NOX4 deletion (NOX4KO) upon a 13-week high-fat diet feeding (60 % of calorie from fat). DKO and NOX4KO mice displayed similar food intake. By contrast, DKO mice displayed less body weight gain than NOX4KO mice due to lower energy efficiency leading to reduced WAT accumulation. DKO mice shifted lipid deposition away from the WAT and enhanced lipid storage in the liver. DKO mice displayed similar fed and starved glucose levels with no alterations in glucose tolerance assessed by intra-peritoneal glucose tolerance tests. Gene expression analysis confirmed a less inflammatory state of both WAT and liver of DKO mice. Our results demonstrate that anti-inflammatory signaling is modulated by NOX4-derived signals in vivo in mice, and that NOX4 and IL-4/IL-13 interaction is a critical component in the regulation surplus lipid storage distribution between WAT and the liver.

Disclosure
I. Szanto: None.

Funding
Insuleman Foundation (ISZ-1); Foundation for the Innovation in Research in Cancer and Biological Sciences
16-OR: Cost-Effectiveness of the 2017 Hypertension Guidelines among U.S. Adults with Diabetes—Results from a Simulation Study
Authors: TANG SHICHAO , SHAO HUI , HOERGER THOMAS J. , ZHANG PING 
Published: June 2023

In 2017, the American College of Cardiology (ACC) and American Heart Association (AHA) changed their guideline for defining hypertension by lowering the blood pressure level threshold from ≥140/90 mmHg to ≥130/80 mmHg. For adults with diabetes and hypertension, initiation of antihypertensive drug treatment was recommended. We used the 2017-March 2020 National Health and Nutrition Examination Survey to create a nationally representative sample of people with diabetes. We used a new diabetes microsimulation model developed by CDC and RTI international to project the lifetime health and cost consequences of implementing this guideline. Hypertension treatments specified in the study follow the guideline. The cost-effectiveness (CE) from a health care system perspective was measured by the incremental CE ratio in terms of cost per quality-adjusted life year (QALY). Under the new guideline, the number of persons with diabetes eligible for treatment would increase from 11.3 million to 20.1 million. Treating these additional patients would increase QALYs by 189,000 and reduce health care cost by $50.7 billion in lifetime. Cost-saving results holds for all subgroups examined (Table). The 2017ACC/AHA guideline yields an additional nearly 9 million people with diabetes recommended for hypertension treatment. Treating this newly eligible population would be cost-saving.

Disclosure
S.Tang: None. H.Shao: Consultant; Lilly Diabetes. T.J.Hoerger: Research Support; Gilead Sciences, Inc. P.Zhang: None.
1605-P: Hepatic Glycogen Directly Regulates Gluconeogenesis in Energy Shortage through AMPK
Authors: ZHANG BICHEN , JOHNSON MORGAN M. , YUAN TIMOTHY , NGUYEN TAMMY-NHU , SALTIEL ALAN 
Published: June 2023

Hierarchical synthesis and breakdown of nutrients in the liver maintain metabolic homeostasis in feeding and fasting cycles. Liver glycogen is the first choice for glucose storage and utilization. Patients with obesity and type 2 diabetes show aberrant hepatic glycogen metabolism, contributing to their increased glucose levels. However, whether and how liver glycogen per se regulates glucose metabolism is unknown. Protein targeting to glycogen (PTG) is the scaffolding protein that controls glycogen metabolism. Here, using a mouse model with liver-specific PTG knockout (LKO), we report that rather than a mere passive reservoir of energy, hepatic glycogen itself senses nutritional and hormonal cues to regulate gluconeogenesis, maintaining sufficient glucose output in energy shortage. Glycogen levels are decreased by 75% in the whole liver and 55% in isolated primary hepatocytes from LKO mice. LKO mice show 40% lower glucose levels in response to short-term fasting because of blunted glycogenolysis. Interestingly, the glucose level is similar in WT and LKO mice after overnight fasting, indicating enhanced gluconeogenesis in LKO mice. In agreement with this, LKO mice show significantly increased glucose production in a pyruvate tolerance test. LKO hepatocytes show increased gene expression of key regulators of gluconeogenesis (Nr4a3, Pgc1a, Pck1) when treated with glucagon or cell-permeable cAMP. Glucose production is also enhanced in LKO hepatocytes with fasting or cAMP treatment. Mechanistically, decreased glycogen levels in LKO hepatocytes increases the activity of AMPK. Pre-treatment of LKO hepatocytes with an AMPK inhibitor abolishes the increase in both gluconeogenic gene expression levels and cellular glucose production. Together, these results reveal a new regulatory role for hepatic glycogen in glucose metabolism, indicating that glycogen is an active molecule that signals the gluconeogenesis pathway through AMPK, to fine tune glucose production during energy shortage.

Disclosure
B.Zhang: None. M.M.Johnson: None. T.Yuan: None. T.Nguyen: None. A.Saltiel: Board Member; Elgia Therapeutics.
1606-P: Tg/HDL Ratio and Liver Fibrosis in Diabetic Patients at an Indian Tertiary Care Center
Authors: CHANDRA ABHISHEK , DINKAR JYOTI , RANJAN RAJEEV 
Published: June 2023

Introduction: According to the most recent International Diabetes Federation (IDF) atlas, there are 537 million persons worldwide who have diabetes. Indians had increased central adiposity and insulin resistance. Diabetes patients are more likely to develop Nonalcoholic Fatty Liver Disease (NAFLD) due to high insulin resistance. An increasingly sensitive indicator of insulin resistance is the TG/HDL ratio. Measuring liver stiffness helps diabetics predict progressive fibrosis. The current investigation uses fibro scans to evaluate the TG/HDL ratio and liver stiffness in diabetic patients.
Methods: After receiving consent, 181 newly diagnosed diabetics underwent fibro scans to measure their liver stiffness. Participants who had already had thiazolidinedione treatment or lipid-lowering therapy were disqualified from the study.
Results: The median stiffness ranged from 2.3 kpa to 34.8 kpa (8.0 kpa), and the median TG/HDL ratio ranged from 0.5 to 29.3 (4.5). The connection between the median stiffness and the TG/HDL ratio was 0.2. Further, 26.5% of participants (Liver stiffness measurement (LSM) &gt; 9.1), 23.7% of subjects who were men, and 30% of subjects who were women, showed advanced fibrosis. Both men and women with LSM &gt; 9.1 had high TG/HDL ratios, with a mean of 4.9 in the former group and 4.9 in the latter. These numbers were significantly higher than the TG/HDL cut-offs for predicting insulin resistance, which were 0.9 and 1.2 for females and males, respectively.
Conclusion: TG/HDL ratio and NAFLD have previously been linked utilising ultrasonography in nondiabetic persons. The more precise and sensitive method for NAFLD screening is the fibro scan. Liver fibrosis is predicted by median stiffness. In the index research, there is a high incidence of advanced fibrosis, which is associated with the TG/HDL
ratio. The TG/HDL ratio was high in all of the male and female individuals with advanced fibrosis.

Disclosure
A. Chandra: None. J. Dinkar: None. R. Ranjan: None.
161-OR: Validation of the Short Type 1 Diabetes Stigma Assessment Scale (DSAS-1) and Its Association with Affective States, Diabetes Distress, Diabetes Self-Management, and Glycemic Control
Authors: CRESPO-RAMOS GLADYS , HOOGENDOORN CLAIRE J. , SCHNEIDER STEFAN , HERNANDEZ RAYMOND , PHAM LOREE T. , PETERS ANNE L. , RUELAS VALERIE F. , CRANDALL JILL P. , LEE PEY-JIUAN , JIN HAOMIAO , PYATAK ELIZABETH , SPRUIJT-METZ DONNA , GONZALEZ JEFFREY S. 
Published: June 2023

Introduction: We validated an 8-item version of the DSAS-1 and examined its relationship with momentary ratings of affective states, diabetes distress, diabetes self-care, and glycemic control over time.
Methods: We recruited 184 adults with T1D from Los Angeles, California, and the Bronx, New York. Participants completed a short version of the DSAS-1, other validated questionnaires, and 10-14 days of intensive longitudinal data collection using blinded continuous glucose monitoring and Ecological Momentary Assessment (EMA) via smartphone. Psychometric validation included exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and internal consistency reliability assessment. We used Spearman's rho correlations to explore the convergent validity using EMA data.
Results: EFA indicated an acceptable fit of a 3-factor model (Bartlett's = 0.000; KMO = 0.774). This was corroborated with CFA, which demonstrated a reasonable three-factor fit (chi-squared = 36.44; RMSEA = 0.079; SRMR = 0.036; TLI = 0.985; CFI = 0.991); less so for a single-factor model. Satisfactory convergent and discriminant validity was demonstrated. The DSAS-1 was significantly correlated with momentary ratings of negative emotions (0.30, p = &lt;0.001), diabetes distress (0.32, p = &lt;0.001), insulin regimen adherence (-0.20, p = 0.007), diabetes self-care (-0.24, p = 0.002), mean blood glucose (0.20, p = 0.008) and time in range (-0.21, p = 0.006), but was not significantly associated with positive emotions.
Conclusions: The 8-item DSAS-1 is a valid and reliable measure of T1D stigma. Convergent validity confirms the importance of diabetes-related stigma in relation to psychosocial and blood glucose outcomes, and underscores the need for further examination of stigma in diabetes, which may be facilitated by this shorter scale.

Disclosure
G.Crespo-ramos: None. H.Jin: None. E.Pyatak: Research Support; Abbott Diabetes. D.Spruijt-metz: None. J.S.Gonzalez: Consultant; Virta Health Corp. C.J.Hoogendoorn: None. S.Schneider: None. R.Hernandez: None. L.T.Pham: None. A.L.Peters: Advisory Panel; Abbott Diabetes, Medscape, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Stock/Shareholder; Omada Health, Inc., Livongo. V.F.Ruelas: None. J.P.Crandall: Research Support; Abbott. P.Lee: None.

Funding
National Institutes of Health (R01DK121298)
1614-P: Metabolomic Profiling Reveals Thiamine-Mediated Regulation of Triglyceride Synthesis and Lipid Turnover in Brown Fat
Authors: WANG CHUNQING , ZHANG XING , LIU MEILIAN 
Published: June 2023

Brown adipose tissue (BAT) functions as a metabolic sink to dispose glucose as well as fatty acids (FAs) and exerts profound effects on energy and glucose homeostasis. Intermittent fasting (IF) has become an attractive option for combating obesity and treating diabetes, yet how IF regimen impacts BAT metabolism and thermogenic capacity remains poorly understood. Using metabolomics and lipidomic assays, we show that alternate day fasting (ADF) elicited robust activation of upper glycolysis and increased production of glycerol-3-phosphate (G3P) and lactate accompanied with stimulation of glycolytic shunts, pentose phosphate pathway (PPP) and glycogenesis, in BAT but not in gonadal white adipose tissue (gWAT) in feeding state. As a result, feast BAT exhibited a notable increase in triglyceride (TG) synthesis, tissue volume, and thermogenic capacity compared to ad libitum group. Mechanistically, repeated fasting and refeeding suppressed the expression of thiamine transporter ThTr2 and decreased the levels of free thiamine, thiamine pyrophosphate (TPP) and thiamine monophosphate (TMP), in part through periodic activation of mTORC1. Genetic inhibition of mTORC1 in BAT restored expression of ThTr2 and diminished ADF-preserved lipid storage in vivo, and inactivating thiamine metabolism with specific inhibitors induced G3P production and TG synthesis in vitro. Taken together, our study reveals a new mechanism involving thiamine that reprograms BAT carbohydrate metabolism to preserve lipids and improves metabolic health.

Disclosure
C.Wang: None. X.Zhang: None. M.Liu: None.
1617-P: Small Intestinal Protein Sensing Mechanism in Feeding and Glucose Regulation
Authors: BARROS DANIEL , LI ROSA J.W. , LIM YUMI , ZHANG SONG-YANG , KUAH RACHEL , GAO ANNA , LAM TONY K. 
Published: June 2023

Protein activates small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase GLP-1, but the role in glucose and feeding regulation remains elusive. We performed intravenous glucose tolerance test and refeeding studies and infused 8% (w/v) casein hydrolysate into the upper small intestine (USI) or ileum of male rats. We found that USI casein vs. saline infusion increased glucose tolerance in chow (p&lt;0.01) and HF-fed rats (p&lt;0.05) and suppressed feeding in chow (p&lt;0.01) but not HF rats. We inhibited CaSR via injecting lentivirus expressing shRNA of CaSR into the USI (reduced expression by ~40%) and CaSR knockdown negated casein to increase glucose tolerance but not to lower feeding (p&lt;0.01). Instead, viral-mediated PepT1 knockdown by ~50% negated casein to lower feeding as similar to previously reported for glucose control. Thus, CaSR and PepT1 are required for casein in the USI to increase glucose tolerance, while PepT1 but not CaSR mediates casein to lower feeding, in chow rats. The differential role of PepT1 vs CaSR may explain why HF disrupts casein to regulate feeding but not glucose tolerance as HF inhibited PepT1 expression (p&lt;0.05) but increased CaSR expression (p&lt;0.05) in the USI. Ileal casein vs saline infusion increased glucose tolerance (p&lt;0.01) and lowered feeding (p&lt;0.01). Ileal CaSR inhibition negated casein vs saline to increase glucose tolerance and lower feeding, whereas ileal PepT1 inhibition failed to do so, indicating that ileal casein regulates glucose tolerance and food intake via PepT1-independent but CaSR-dependent pathways in chow rats. HF feeding inhibited ileal CaSR expression by ~60% (p&lt;0.05) in association with a disruption in ileal casein action on feeding but surprisingly not on glucose control (p&lt;0.01), suggesting that ileal casein could even regulate glucose tolerance independent of CaSR. In sum, we discover differential role of CaSR vs. PepT1 in the USI and ileum that alter feeding and glucose regulatory abilities of protein sensing.

Disclosure
D.Barros: None. R.J.W.Li: None. Y.Lim: None. S.Zhang: None. R.Kuah: None. A.Gao: None. T.K.Lam: None.

Funding
Canadian Institutes of Health Research (PJT183901)