bluuebunny/crossref_metadata_2025_split huggingface dataset:
1656-P: Glucagon-Like peptide-1 (GLP-1) Secretion from Intestinal L-Cells Is Mediated by hERG Potassium Channels
Authors: YANG JIN-KUI , LIU CHANG , WANG HAO , YUAN YINGCHAO 
Published: June 2023

The hERG protein is a member of voltage-gated potassium (Kv) channels. Previous reports showed that patients with long QT syndrome due to mutations in hERG channel had higher responsive glucagon-like peptide-1 (GLP-1) secretion. However, the role of hERG in GLP-1 secretion remains uncertain. Here we report that hERG is co-expressed in GLP-1-expressing L cells in rodent intestinal epithelium (Fig. 1). In a murine L-cell model, GLUTag cell line, downregulation of hERG significantly prolonged action potential duration, increased intracellular calcium concentration ([Ca2+]i), and promoted GLP-1 secretion (Fig. 2) after stimulation of nutrients. These results reveal a direct role of hERG in GLP-1 secretion in murine L-cells, suggesting intestinal hERG is a potential target for the treatment of diabetes.

Disclosure
J.Yang: None. C.Liu: None. H.Wang: None. Y.Yuan: None.

Funding
National Natural Science Foundation of China (82170809, 81930019)
166-LB: Clinical Improvements and Extracellular Vesicle Size following Lifestyle Intervention in Latino Youth with Nonalcoholic Fatty Liver Disease
Authors: PIRAS IGNAZIO , WU XIUMEI , PIRROTTE PATRICK , OLSON MICAH , KHAN SOOFIA , XANTHAKOS STAVRA , SHAIBI GABRIEL Q. , DISTEFANO JOHANNA 
Published: June 2023

Latino youths with obesity are disproportionately impacted by nonalcoholic fatty liver disease (NAFLD). Lifestyle intervention can improve established biomarkers such as serum transaminases and hepatic fat fraction (HFF) in NAFLD patients. Circulating levels of extracellular vesicles (EVs) have been associated with NAFLD and may track with changes in liver fat. Here we assessed changes in EV concentration and size following a comprehensive lifestyle intervention in 18 Latino adolescents (12 males/6 females; average age 13.3 ±1.2y) with obesity and NAFLD, as defined by MRI-measured hepatic fat fraction (HFF) ≥5%. Participants completed a 6-month lifestyle intervention that targeted improvements in eating behaviors (e.g., decreased sugar and saturated fat intake, portion control, and increased fiber intake) and increases in physical activity. EVs were isolated from fasting plasma samples taken at baseline and following intervention using size exclusion chromatography and characterized by nanoparticle tracking analysis. Significant improvements (pre- vs post-intervention) were observed in percent body fat (44.7 ±4.8% vs 42.2 ±5.3%, p&lt;0.0001), alanine transaminase (ALT; 24.8 ±7.4 U/L vs 23.2 ±5.6 U/L p=0.02), and HFF (12.5 ±5.5% vs 9.6 ±4.9%, p=0.008). We observed a significant reduction in mean EV size (128.4 ±16.5 vs 120.2 ±16.4, p=0.03) and a non-significant reduction in EV concentration (1.14E+09 ±4.1E+08 vs 1.09E+09 ±1.8E+08, p=0.61) following the intervention. Change in mean EV size was significantly and positively associated with changes in SAT (cm3), HDL (mg/dl), fat (kg) and BMI (all p &lt; 0.05). These results suggest that improvements in NAFLD-related phenotypes following lifestyle intervention correspond with reductions in EV size in Latino adolescents with obesity and NAFLD.

Disclosure
I. Piras: None. X. Wu: None. P. Pirrotte: None. M. Olson: Advisory Panel; Rhythm Pharmaceuticals, Inc. S. Khan: None. S. Xanthakos: None. G. Q. Shaibi: None. J. Distefano: None.

Funding
National Institutes of Health (R01DK127015)
1666-P: ScRNAseq–Based Analysis of the Stromal Immune Cell Composition in Murine Preweaning and Adult White Adipose Tissues
Authors: YAN XIAOCHENG , MIOK VIKTORIAN , KARLINA RUTH , BÖTTCHER ANIKA , LUTTER DOMINIK , LICKERT HEIKO , GARCIA CACERES CRISTINA , USSAR SIEGFRIED 
Published: June 2023

Early postnatal adipose growth is essential to establish a functional metabolism. Conversely, proportional adipose expansion in adults results in insulin resistance. Despite adipocytes, immune cells play a pivotal role in orchestrating adipose tissue function and expansion. To this end, we performed an in-depth analysis of scRNAseq data of immune cell populations of 2 weeks (pre-weaning) and 8 weeks old (adult) murine subcutaneous and perigonadal adipose depots. Our analysis revealed 15 distinct immune cell clusters. Most immune cell types were found in all depots and ages. Among the detected T-cell populations, we only observed differences in the abundance of naïve T cells, which were predominantly found in in subcutaneous white adipose tissue, irrespective of age. Similar to human, we could define several murine macrophage subtypes. Among them, perivascular macrophages (PVM) were predominantly found in subcutaneous white adipose tissue of 2 weeks old mice. RNA-velocity analysis and pseudotime trajectory construction suggested a developmental trajectory from lipid-associated macrophages (LAM) to PVM, which was further corroborated by analysis of gene expression dynamics resolved along latent time of white adipose tissue macrophages from 2 weeks old mice. Further analysis revealed that the top-ranked 100 genes of LAM were associated with the regulation of endothelial cell migration and proliferation (Nrp1, Grn, Glul, Sash1, Ccl24), blood vessel morphogenesis (Nrp1, Tgfbr2) and the regulation of epithelial cell proliferation.
In summary, we provide a comprehensive overview of the immune cell composition of pre-weaning and adults murine adipose tissues. Moreover, we provide in-depth analysis of T-cell and macrophage populations and their relationship and dependency based on mRNA expression analysis.

Disclosure
X. Yan: None. V. Miok: None. R. Karlina: None. A. Böttcher: None. D. Lutter: None. H. Lickert: Research Support; Eli Lilly and Company. C. Garcia Caceres: None. S. Ussar: Research Support; Novo Nordisk.

Funding
China Scholarship Council (201908370218)
168-LB: A Randomized Crossover Trial Comparing Glucose Control between Different Exercise Types in Adolescents with Type 1 Diabetes Using a Hybrid Closed-Loop System
Authors: SECKOLD ROWEN , MORRISON DALE , RAFFERTY JORDAN , VALKENBORGHS SARAH R. , PALDUS BARBORA , ZAHARIEVA DESSI P. , RIDDELL MICHAEL C. , SMART CARMEL E. , O'NEAL DAVID N. , KING BRUCE R. 
Published: June 2023

Background: Hybrid closed loop (HCL) systems may mitigate the glycemic impact of different exercise types in youth with type 1 Diabetes.
Aims: Glucose was compared during and following moderate intensity exercise (MIE), high intensity interval exercise (HIE) and resistance exercise (RE) in adolescents using HCL insulin delivery.
Methods: Adolescents using HCL (Medtronic Minimed 670G) undertook 40 min of MIE, HIE and RE in random order. A temporary glucose target was set 2 hours prior and during exercise with 15g carbohydrate given pre-exercise if glucose level was &lt;126mg/dL. A standardized dinner was eaten 4 hours after exercise. The primary outcome was sensor glucose percentage time in range 70-180mg/dL (TIR) for 12 hours from exercise onset.
Results: Twenty-eight participants (50% female); age [mean (SD)] 16.3(2.1) years; diabetes duration 9.4(4) years; HbA1c 7.3(0.6)% [56(7)mmol/mol], completed the study. In the 12 hrs following exercise onset the TIR for MIE was [median (IQR)] 76(60-92)%, HIE 87(78-96)% and RE 85(69-94)% (MIE v HIE; (p=0.015). Time &gt;180mg/dL (TAR) was greater for MIE v HIE (18[3-25]% v 7[0-15]%; p=0.041). Time &lt;70mg/dL (TBR) did not differ between MIE, HIE and RE [0 (0-7)%; 2(0-9)%; and 2(0-10)% respectively]. After the post-exercise meal (280-715mins), TIR for MIE was lower than HIE [86(76-96) v 67(49-87)%; p=0.003] and TAR was higher for MIE than HIE [5(0-19) v 28(0-41)%; p=0.012]. There was no significant difference between exercise types in TIR, TAR and TBR during exercise (0-40min) and before dinner (40-280mins). There was a total of 8 episodes of hypoglycemia (15mins &lt;54mg/dL) each for MIE and RE and 5 for HIE.
Conclusion: Glucose control in the post meal period following exercise differed between HIE and MIE but not RE. Hypoglycemia occurred across all exercise types.

Disclosure
R. Seckold: None. D. Morrison: None. J. Rafferty: None. S. R. Valkenborghs: None. B. Paldus: None. D. P. Zaharieva: Speaker's Bureau; American Diabetes Association. Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Ascensia Diabetes Care, Medtronic. M. C. Riddell: Stock/Shareholder; Supersapiens. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Consultant; Lilly Diabetes. Speaker's Bureau; Novo Nordisk, Sanofi. Stock/Shareholder; Zucara Therapeutics. Advisory Panel; Zucara Therapeutics, Indigo Diabetes. Consultant; Eli Lilly and Company, Jaeb Center for Health Research. C. E. Smart: None. D. N. O'Neal: None. B. R. King: None.

Funding
JDRF (3-SRA-2018-532-M-B)
168-OR: Marked Variability of Starting Insulin Algorithms for Noncritical Illness—A Survey of 32 Academic Hospitals in the United States
Authors: CHIANG HOU-HSIEN , KAHN STEVEN E. , HIRSCH IRL B. 
Published: June 2023

Glycemic control immediately after hospitalization is difficult, with blood glucose within 24 hours after admission often above recommended targets. Further, it takes time to adjust and determine individual insulin requirements. Endocrine Society guidelines suggest starting scheduled insulin therapy at 0.2–0.5 units/kg body weight as the total daily dose, but there has been no rigorous study to support this guideline and other institutional algorithms. To understand the variability of current practice, we conducted a survey of starting insulin algorithms for non-critically ill patients among top-ranking hospitals and endocrinology programs in the US.
Among the 32 hospitals surveyed, replies were received from 25. Of these, 19 provided their algorithms, 5 stated they did not have such, and one used a proprietary (commercial) algorithm. The figure details the number of algorithms specifying basal/nutritional insulin regimens versus only correction insulin, approaches to calculating the basal/nutritional dose, and guides to choosing correction algorithms.
In summary, amongst US academic hospitals there is great variability in methods for determining starting insulin dosing on admission for non-critically ill patients. This inconsistency suggests that a clinical trial is required to determine the best approach(es) to estimating initial insulin requirements.

Disclosure
H.Chiang: None. S.E.Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Other Relationship; Novo Nordisk. I.B.Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc.

Funding
National Institutes of Health (5T32DK007247-45)
169-LB: Neuropsychological Consultation and Glycemic Control in Pediatric Patients
Authors: GONZALEZ JUANA E. , STEIN CHERYL R. , ILKOWITZ JENIECE , POWELL SARAH , PAT GALLAGHER MARY 
Published: June 2023

Executive function underlies the ability to plan, reason, and problem solve - skills essential to diabetes management. Children with T1D are at elevated risk of executive dysfunction. Providing families with supports to acknowledge and address these deficits may improve diabetes outcomes. In a randomized controlled trial, we evaluated whether neuropsychological consultation improved glycemic control.
From July 2019-September 2020 we enrolled patients aged 10-17 years with T1D ≥6 months. Participants were randomized at enrollment to neuropsychological consultation (n=26) or usual care (n=24). Both groups completed executive function and psychosocial assessments at baseline and follow-up plus received diabetes management education. The intervention group also underwent neuropsychological consultation followed by focused feedback. Follow-up for both groups extended for 12 months. We assessed whether neuropsychological consultation was associated with change in HbA1C from baseline to follow-up using age and sex-adjusted linear regression models in intention-to-treat and per protocol analyses.
At baseline, the mean (SD) age of participants was 13.8 (2.4) years with 51% in grades 5-8 and 49% in grades 9-12. Mean (SD) HbA1c was 7.7% (1.7); most participants used CGMs (94%) and insulin pumps (87%). Thirty-five percent of the intervention group met criteria for executive dysfunction. HbA1C was lower at follow-up in the treatment group according to both the intention-to-treat (-1.3%; 95% CI -2.5, -0.1) and per protocol (-1.3%; 95% CI -2.6, 0.1) analyses.
This small randomized controlled trial performed primarily during the COVID-19 pandemic demonstrates that neuropsychological consultation may contribute to improvement in glycemic control among pediatric patients with T1D. Next steps include examining changes in psychosocial outcomes, identifying the most impactful aspects of the consultation, and studying this intervention in a larger patient population.

Disclosure
J. E. Gonzalez: None. C. R. Stein: None. J. Ilkowitz: None. S. Powell: None. M. Gallagher: None.
169-OR: SGLT2 Inhibitor Prescribing Discrepancies in Patients with Diabetes Mellitus Type 2 and Heart Failure at an Academic Medical Center
Authors: HANSEN JESSICA , KULASA KRISTEN , SANTOS CAVAIOLA TRICIA 
Published: June 2023

With new indications for SGLT-2 inhibitors (SGLT2i) and efforts to minimize cardiovascular risk, there are concerns about equitable and timely distribution of SGLT2i. Inpatient initiation of SGLT2i is an important opportunity to optimize medical therapy. To better understand current prescribing practices, we compared patients started on a SGLT2i at time of discharge across two hospital sites in the 15 months after inclusion in the inpatient medication formulary. A retrospective chart review from February 2021 to May 2022 was performed of patients admitted to UC San Diego and discharged with a SGLT2i. Diagnosis was determined by ICD-10 code, and/or A1c during admission 6.5%. This cohort was compared to all patients admitted with an ICD-10 diagnosis of heart failure and/or DMT2. We examined patient demographics including age, gender, race/ethnicity, and differences between hospital sites (H1, H2). An SGLT2i was prescribed for 178 patients out of 1160 total admissions for CHF and 52,291 total admissions of individuals with DMT2. Of those who received an SGLT2i, 105 (58%) had diabetes, 151 (85%) had CHF and 82 (46%) had both. Between hospitals, 22% of patients with CHF at H1 v. 5% at H2 received an SGLT2i, and 0.22% of patients with diabetes at H1 and 0.17% at H2. The average age of those prescribed compared to the eligible population was 59 v. 64 for CHF and 60 v. 47 for DMT2. Women were less likely to be prescribed than men in both the heart failure (7% v. 16%) and DMT2 groups (0.1% v. 0.32%). The percentage of recipients (CHF, DMT2) by ethnicity was Asian (6, 0.08%), American Indian 0%, Black (7, 0.23%), Hispanic (19, 0.23%), Pacific Islander (26%, 0.81%), White 10, 0.17%). This analysis of SGLT2i initiation at hospital discharge indicates there are likely key differences in prescribing frequency between gender, ethnicities, and hospital sites. Continued collaboration amongst specialties and attention to implicit bias in prescribing practices is warranted.

Disclosure
J.Hansen: None. K.Kulasa: None. T.Santos cavaiola: Consultant; 9am Health.
1718-P: Association between Sleep Habits and Overweight among Adolescents in Japan
Authors: SHIOZAKI HARUKA , FUJIHARA KAZUYA , TAKEDA YASUNAGA , IKEDA IZUMI , MORIKAWA SAKIKO Y. , TSURUOKA KAHORI , KODERA REMI , MON KHIN LAY , WU SIJIA , FERREIRA EFREM D. , ISHIGURO HAJIME , OGAWA YOHEI , SONE HIROHITO 
Published: June 2023

Insufficient sleep and late bedtime are associated with deteriorating glucose tolerance status, diabetes and overweight. Although lifestyle in adulthood is influenced by childhood and adolescent experiences, little is known about the association between sleep habits and glucose status in children. Thus, we investigated the association between sleep habits and overweight in 1050 Japanese adolescents (497 boys) considering the effects of diet, physical activity and screen time. Overweight was defined by the International Obesity Task Force. Sleep duration and wake/sleep time were based on questionnaires, and their association with overweight was analyzed by logistic regression. On weekends, girls with overweight had short sleep duration. In a univariate analysis of participants divided into 4 groups, the relationship between sleep habits and overweight did not present a U- or J-shaped curve. We conducted a multivariate logistic regression analysis based on the median bedtime of 23:00 and sleep duration of 9 h. In boys, there was no association between sleep habits and overweight. The odds ratios for overweight in girls with long sleep duration were high regardless of bedtime (early bedtime: odds ratio 3.42 [95% CI 1.15-10.17]; late bedtime 3.08 [1.14-8.33]). Gender differences exist in the association between sleep habits and overweight. In Japanese adolescent girls, sufficient sleep duration on weekends may be necessary.

Disclosure
H.Shiozaki: None. E.D.Ferreira: None. H.Ishiguro: None. Y.Ogawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. Y.Takeda: None. I.Ikeda: None. S.Y.Morikawa: None. K.Tsuruoka: None. R.Kodera: None. L.Khin: None. S.Wu: None.
172-LB: Traditional Risk Factors for Elevated A1C Persist among Youth with T1D Using CGM—Results from the 4T Study 1
Authors: KIM JAEHYUN , ZAHARIEVA DESSI P. , BISHOP FRANZISKA K. , SCHEINKER DAVID , JOHARI RAMESH , DESAI MANISHA , HOOD KOREY K. , MAAHS DAVID M. , ADDALA ANANTA 
Published: June 2023

Continuous glucose monitoring (CGM) use soon after T1D diagnosis in the 4T Study was associated with improved glycemic outcomes. We evaluated participant factors associated with elevated versus in target A1c for youth in the 4T Study.
All youth from the 4T Study 1 (n=133) were evaluated. In this analysis, the 110 youth who had a final A1c between 6-13 months were included in a complete case analysis. These 110 youth were comparable to the 133 4T Study 1 youth by race/ethnicity, insurance, preferred language, and age. Group differences by non-ordered A1c categories were evaluated for categorical (race/ethnicity, insurance, gender, and language) and continuous (age and time from CGM start) variables via chi-square and ANOVA, respectively.
A majority of youth in the 4T Study 1 met glycemic targets (65% with A1c ≤7% between 6-13 months post-diagnosis). Age, race/ethnicity, and insurance status were significantly associated with A1c categories (p=0.02 for all; Table). Higher A1c categories were more likely to include Hispanic youth and youth with public insurance.
In the 4T Study 1, Hispanic youth and youth with public insurance had higher A1c categories despite similar CGM access and training. These findings suggest the need to address additional drivers of disparities in addition to CGM access. Approaches focused on health equity are required to improve glycemic outcomes in all youth newly diagnosed with T1D.

Disclosure
J. Kim: None. D. P. Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. F. K. Bishop: None. D. Scheinker: None. R. Johari: None. M. Desai: None. K. K. Hood: Consultant; Cecelia Health. D. M. Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. A. Addala: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK13134201, R18DK122422)
1720-P: Metabolic Response to Bariatric Surgery of Novel High-Risk Prediabetes Subphenotypes
Authors: SZCZERBINSKI LUKASZ , GOSCIK JOANNA , KWEDLO WOJCIECH , WOJCIECHOWSKA GLADYS E.P. , CITKO ANNA , KONOPKA PAULINA , PASZKO ADAM , TAYLOR MARK , HADY HADY R. , KRETOWSKI ADAM J. 
Published: June 2023

A novel pathophysiology-based method to subphenotype individuals at elevated risk for type 2 diabetes has recently identified 6 subgroups, 2 of which constitute obese, high-risk subpopulations with different glycemic, renal, cardiovascular and all-cause mortality risk profiles. The aim of our study was to evaluate differences in response to weight-loss surgery between these clusters, termed clusters 5 & 6 by Wagner et al. We performed this clustering on the Bialystok Bariatric Surgery Study Cohort consisting of nondiabetic patients with at least one year of follow-up data who underwent sleeve gastrectomy surgery. We used generalized linear models to test for differences between clusters in baseline parameters and changes after one year. At baseline, 48 (47%) patients were classified as cluster 5 and 54 (53%) as cluster 6. Before the surgery, cluster 5 subjects had significantly (q-value&lt;0.05) higher levels of fasting and 2-hour glucose and insulin, HbA1c, triglycerides and visceral fat mass, and lower levels of HDL-cholesterol and Matsuda Index. There were no significant differences in age, weight, BMI or body composition. Further, we found that cluster 5 presented a greater reduction in fasting and 2-h glucose, but lesser in hip and waist circumferences, compared to cluster 6. However, after adjusting for baseline values of these parameters, only change in hip and waist circumferences remained significant. We did not find any differences in body composition or lipid parameter responses between clusters. Our study confirms that cluster 5 shows more severe glycemic and lipid deterioration compared to cluster 6 despite their shared obese phenotypes. However, bariatric surgery seems to be equally beneficial in both clusters, except for small differences in hip and waist circumference response.

Disclosure
L. Szczerbinski: None. J. Goscik: None. W. Kwedlo: None. G.E.P. Wojciechowska: None. A. Citko: None. P. Konopka: None. A. Paszko: None. M. Taylor: None. H.R. Hady: None. A.J. Kretowski: None.