bluuebunny/crossref_metadata_2025_split huggingface dataset:
370-P: Anxiety and Depressive Symptoms of Type 1 Diabetes and Severe Hypoglycemia in Adult Continuous Glucose Monitor Users
Authors: BOATENG-KUFFOUR ADRIANA , CALLAHAN PATRICK , CHANDARANA KEVAL , GUPTA TINA , CHEN LIANG , KELLY CAITLIN S. , NGUYEN HUYEN , CHAPMAN KATHERINE S.M. , CORNELIUS EMILEE M. , WOLF WENDY , POLONSKY WILLIAM H. 
Published: June 2024

Introduction & Objective: Anxiety and depression are common in type 1 diabetes (T1D), but literature regarding their association with severe hypoglycemic events (SHE) and impaired awareness of hypoglycemia (IAH) is limited.
Methods: Adult (≥18 years old) continuous glucose monitor users in the T1D Exchange Registry completed online survey measures of SHE frequency, IAH, and anxiety/depression symptoms (PHQ-4). SHE cohorts were created based on SHE frequency in the past 12 months and IAH status (defined in the Table). Descriptive results (mean, standard deviation) were reported. Bivariate correlations between anxiety/depression with SHE frequency and IAH were examined using Pearson’s correlation. R
esults: Overall, higher SHE frequency was significantly associated with higher anxiety/depression (ranxiety=0.09, rdepression=0.08, rPHQ-4Total=0.09, all p&lt;0.001); however, correlation coefficients were small. There was no significant relationship between anxiety/depression and IAH (p range=0.10-0.71). The problematic SHE cohort had higher reported anxiety/depression means (Table).
Conclusion: Although higher SHE frequency was associated with a small increase of anxiety/depressive symptoms, IAH alone was not. Findings highlight the need to better understand the complex relationship between SHE and IAH in the experience of anxiety/depression in adults with T1D.

Disclosure
A. Boateng-Kuffour: Employee; Vertex Pharmaceuticals Incorporated. P. Callahan: Employee; Vertex Pharmaceuticals Incorporated. K. Chandarana: Employee; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Vertex Pharmaceuticals Incorporated, Novo Nordisk, Eli Lilly and Company. T. Gupta: Employee; Vertex Pharmaceuticals Incorporated. L. Chen: None. C.S. Kelly: None. H. Nguyen: None. K.S.M. Chapman: None. E.M. Cornelius: None. W. Wolf: None. W.H. Polonsky: Research Support; Abbott Diagnostics, Dexcom, Inc. Consultant; Eli Lilly and Company, Sanofi. Advisory Panel; embecta. Consultant; Vertex Pharmaceuticals Incorporated. Advisory Panel; 9am Health.

Funding
Vertex Pharmaceuticals Incorporated
378-P: Frequency of Nocturnal Hypoglycaemia in Adults with Insulin-Treated Diabetes and Adrenal Failure Using Prednisolone or Hydrocortisone—A Pilot Study
Authors: KHAN SHAILA , REDDY MONIKA , OLIVER NICK , MCKECHNIE VICKY , AVARI PARIZAD 
Published: June 2024

Introduction: Adrenal insufficiency (AI) is a potentially life-threatening condition associated with increased mortality, necessitating lifelong steroid replacement, typically with hydrocortisone or prednisolone. This pilot study investigates the frequency of nocturnal hypoglycaemia in adults with insulin-treated diabetes mellitus (DM) and AI, comparing the effects of prednisolone and hydrocortisone. The study aims to explore potential factors contributing to the mortality excess observed in this population.
Methods: This was a prospective observational study recruiting adults with insulin-treated DM and AI, and a control group with AI without DM. Participants were matched for age, sex, and steroid replacement. Participants were provided with continuous glucose monitoring (CGM; Dexcom G6) for 30 days and data were analysed for percentage times in range.
Results: Amongst 27 participants with AI recruited, 13 were female, mean age was 54.7±8.9 years and 13 also lived with DM. Of these, median time spent in nocturnal hypoglycaemia (&lt;3.9mmol/L) was 0.7% (0.5% with hydrocortisone, 0.8% with prednisolone. Statistically significant differences were not found between prednisolone and hydrocortisone users. Clinically significant findings revealed higher time above 10mmol/L and lower time in the target range (3.9-10mmol/L) in participants with DM taking prednisolone.
Conclusion: We present the first data on glycaemic patterns from CGM in individuals with both DM and AI, establishing pilot data for nocturnal and diurnal hypoglycaemia. Potentially clinically important hyperglycaemia was identified in those living with DM on prednisolone. These findings highlight the need for larger sample sizes to explore potential implications for cardiovascular risk and mortality in this vulnerable population. The findings contribute novel insights aiming to enhance patient safety in managing both DM and AI.

Disclosure
S. Khan: None. M. Reddy: None. N. Oliver: Advisory Panel; Dexcom, Inc., Medtronic, Roche Diabetes Care. Speaker's Bureau; Sanofi, Tandem Diabetes Care, Inc. Research Support; Dexcom, Inc., Medtronic. V. McKechnie: None. P. Avari: None.

Funding
Imperial Health Charity UK
379-P: Population Response to Home Use of Mini-dose Glucagon as a Treatment for Hypoglycemia following Repeated, Prolonged Fasts in Type 1 Diabetes during Ramadan
Authors: ALGEFFARI METAB , HUSSAIN SUFYAN , ALSHARIDAH MANSOUR , ALKHALIFAH SALSABIL , ALMOGBEL TURKI 
Published: June 2024

Objective: The extent of public interest of home use of mini-dose glucagon (MDG) as a new approach for managing hypoglycemia during Ramadan prolonged fasts prompted the authors to make available, on a on social media, general information about study protocol, both for people with diabetes and healthcare professionals. Shortly thereafter, individuals began to feed back their personal experiences. We have collated this information using a structured online survey outside a research setting
Methods: Emails, private messages in X (twitter) and WhatsApp communications between May 2021 and April 2023 were evaluated (n = 136). An online survey was sent to collect the feedback of using MDG
Results: After using MDG, 123 (91%) of participants reported they were able to complete their fasts and 110 (80%) of participants they report will prefer to use MDG in the future to correct fasting induced hypoglycemia. Furthermore, participants showed significant change in their habits with more than half stop raise their blood sugar above the target at Sahour time and more than half start to correct the previous ignored hypoglycemia even if it was occurred within an hour of Iftar time
Conclusions: These data demonstrate that MDG administration is an effective as home treatment for fasting-induced hypoglycemia and encourage the change of unhealthy habits to avoid breaking the fast

Disclosure
M. Algeffari: None. S. Hussain: None. M. Alsharidah: None. S. Alkhalifah: None. T. Almogbel: None.

Funding
Qassim University, represented by the Deanship of Scientific Research, on the financial support for this research under the number (#5389-med-2019-2-2-I) during the academic year 2019
386-P: eGFR, Cardiometabolic, and Prediabetes Risk in Healthy Subjects
Authors: BRAWLEY BLAIR W. , BROWN LOUIS , ASUZU PEACE , DAGOGO-JACK SAMUEL 
Published: June 2024

Introduction and Objective: We examined kidney function (eGFR) in relation to cardiometabolic risk factors (CMRFs) and incident prediabetes in healthy subjects.
Methods: Participants were normoglycemic Black and White offspring of parents with type 2 diabetes followed for 5 years in the POP-ABC study. Assessments included clinical exam, OGTT, chemistries, lipids, insulin sensitivity (ISI, by euglycemic clamp), insulin secretion (AIRg) and disposition index (DI=AIRg x ISI). The CKD-EPI equation was used to estimate eGFR (ml/min/1.73m2) at baseline. Participants were grouped by the presence of 3 or more metabolic syndrome (MetS)components into MetS or NonMetS groups.
Results: We studied 296 subjects (73% female; 138 Black, 158 White), mean age 45.5 ± 10.1 yr, and BMI 30.5 ± 7.6 kg/m2. Individuals with MetS had higher baseline eGFR versus NonMetS (112 ± 18.2 vs. 101 ± 18.4, P= 0.0002). eGFR correlated with waist circumference (men: r=0.26, P=0.02; women: r=0.40, P&lt;0.0001) and HDL (women: r= -0.42, P&lt;.0001; men: r= -0.17; P=0.106), but not systolic BP (r=0.06, P=0.32), diastolic BP (r=0.07, P=0.23), or triglycerides (r=0.06, P=0.30). eGFR levels increased with cumulative MetS components (PANOVA= 0.0002). Baseline eGFR values were significantly higher in participants who progressed to prediabetes during 5-yr follow-up vs. nonprogressors (107 ± 18.5 vs. 100 ± 18.5, P=0.003) and significantly associated with incident prediabetes (Z= -14.9, P&lt;0.0001).
Conclusion: Among healthy persons with normal glucose and eGFR levels, we observed a significant association between eGFR and some cardiometabolic risk markers and incident prediabetes. Thus, variations in eGFR within the normal reference range among healthy people might convey significant cardiometabolic information. Further studies are needed to unravel the mechanisms linking variations within normal eGFR range and metabolic dysregulation.

Disclosure
B.W. Brawley: None. L. Brown: None. P. Asuzu: None. S. Dagogo-Jack: Consultant; Merck Sharp & Dohme Corp., Medtronic, Bayer Inc. Stock/Shareholder; Aerami.
389-P: ChREBP-ß Aggravates Fructose-Induced Renal Tubular Reabsorption Disorder by Regulating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction
Authors: SUN BEI , FANG TING , CHEN LIMING 
Published: June 2024

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is essential for fructose metabolism in mice. Renal fructose metabolism occurs mainly in the renal tubules. As a constitutively active form, ChREBP-β is expressed at extremely low levels. To date, the functional significance of ChREBP-β in renal fructose metabolism remains unclear. Here, we show that ChREBP-β regulates fructose-induced renal tubular reabsorption disorder by controlling endoplasmic reticulum stress and mitochondrial respiration. Kidney ChREBP-β mRNA levels were elevated upon fructose exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in renal tubules. ChREBP-β overexpression led to renal tubular reabsorption disorder, as evidenced by increased markers NAG and β2-MG and rupture of the brush border of the renal tubule. Mechanistically, ChREBP-β overexpression upregulated the expression of genes like ATF4 involved in endoplasmic reticulum stress and downregulated those involved in mitochondrial respiration. Furthermore, apoptosis gene expression was markedly activated in the kidney by ChREBP-β overexpression. Taken together, our work establishes a critical role of kidney ChREBP-β in coping with renal tubular reabsorption disorder.

Disclosure
B. Sun: None. T. Fang: None. L. Chen: None.
4-PUB: Exploring the Utility of Non-HDL/HDL Ratio to Predict Nonalcoholic Steatohepatitis (NASH) and Its Progression in People with Diabetes Using FibroScan-AST (FAST) Scores in a Tertiary Care Center in India
Authors: TEWARI AJOY , MAHESHWARI ANUJ , TEWARI JAY , TEWARI VINEETA 
Published: June 2024

Introduction: ICMR INDIAB study (2023), found the prevalence of diabetes in India as11.4%. NAFLD is highly prevalent in people with diabetes. NASH is characterised by hepatocyte ballooning, lobular inflammation bridging necrosis, denotes a progressive liver disease. Newsome et al., postulated Fibro scan-AST (FAST) scores to detect NASH, elevated NAFLD activity score (NAS more than 4) and significantly more than F2 on liver biopsy. The nonHDLc to HDLc ratio may show combined lipid problems and was found to be a better predictor for multiple dyslipidemia-related disorders, such as coronary heart disease (CHD), insulin resistance, metabolic syndrome and chronic kidney disease than relying on single lipoprotein or the apoB/apoA1 ratio.
Aim: To assess the prevalence of NASH in people with diabetes using FAST scores in a tertiary care centre in India and its correlation with nonHDL/HDL ratio.
Material and Methods: Fibroscan was used to measure liver stiffness measurements in 229 people with diabetes. Current Hba1c and lipid profile, AST, were recorded and used to calculate Non HDL/HDL ratio and FAST scores.
Results: index study had 48% males and 52% females, mean age was 50.2 years, duration of diabetes was 7.9years, mean Hba1c was 8.7%, median stiffness was 8.7kpa, BMI 27.5%, WC was97.12 cm.167 (72%) had a FAST score of equal to less than 0.35 predicting low probability of NASH,50 (21.8%) people had indeterminate FAST scores (0.35 -0.67), and 12 (6.2%) people with diabetes had a FAST score of more than or equal to 0.67, denoting high probability of NASH. FAST scores correlated positively with Non HDL/HDL ratio at a correlation coefficient of .137, which was statistically significant (p&lt;0.05).
Conclusion: Non HDL /HDL ratio, an easy to perform test in routine clinical practice, can be used to evaluate for NASH and more severe stages of NAFLD in people with diabetes.

Disclosure
A. Tewari: None. A. Maheshwari: None. J. Tewari: None. V. Tewari: None.
402-P: Effect of Serum 25-Hydroxyvitamin D on CKD Progression in Type 2 diabetes
Authors: ZHANG CHENGHUI , SUYUAN WANG , LI MINGXIA 
Published: June 2024

Background: It has been established that there was an inverse association between baseline serum 25-hydroxyvitamin D (25OHD) and new-onset chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). However, the prospective relationship between vitamin D status and CKD progression remains uncertain. We aimed to investigate the association between 25OHD level and the progression of CKD in patients with T2D.
Methods: In this prospective, observational study, patients with T2D aged 18-79, who had received regular medical examination for at least a year were consecutively enrolled. Physical findings and laboratory data of patients were collected annually. Serum 25OHD concentrations were measured using chemiluminescent immunoassay method. The primary outcome was CKD progression, defined as a change of at least 1 CKD stage or incidence of macroalbuminuria or new-onset end-stage renal disease. The risk of CKD progression according to 25OHD was analyzed by Cox proportional hazard models.
Results: A total of 245 patients were enrolled in this study. The mean age was 59 years, with a majority of 179 (73%) being male participants. The baseline 25OHD connection was measured at 16.4 (7.1) ng/ml. Over a median follow-up period of 2.1 years, 38 subjects (16.5%) developed CKD progression. After adjusting for gender, age, diabetic duration, BMI, systolic blood pressure, HbA1c, LDL-C, baseline eGFR, serum concentrations of 25OHD was associated with 7% lower risk of CKD progression per every 1ng/ml increase (HR: 0.93, 95%CI: 0.86-0.99, P=0.036).
Conclusion: Serum 25OHD was found to be an independent protective factor for CKD progression in patients with type 2 diabetes.

Disclosure
C. Zhang: None. W. Suyuan: None. M. Li: None.

Funding
Science and Technology Project of Tibet Autonomous Region (XZ202201ZR0037G)
41-OR: Insulin Regulates Exosomal MicroRNA Secretion from Adipocytes Completing a Novel Feedback Loop
Authors: LINO MARSEL , GARCIA MARTIN RUBEN , MUÑOZ VITOR , BRANDAO BRUNA B. , RONALD KAHN C. 
Published: June 2024

MicroRNAs (miRNAs) are critical regulators of gene expression. MiRNAs are also secreted by tissues in small extracellular vesicles known as exosomes and can act at a distance. We have shown that adipose tissue is a major source of circulating exosomal miRNAs and that some of these are taken up by distal organs, like the liver, where they regulate key metabolic genes. We have also shown that miRNA loading into exosomes is a tightly regulated process that involves the recognition of 4-8 nucleotide motifs by RNA binding proteins. Thus, exosomal miRNAs have the potential to act as endocrine factors, leading us to ask whether insulin regulates their secretion by adipocytes. To this end, we performed small RNA-seq on exosomes from differentiated 3T3-L1 adipocytes with and without insulin stimulation. Insulin induced the secretion of 52 miRNAs, including multiple members of the let-7 family, the miR-182/183 cluster, as well as miR-103-3p, miR-146b-5p, and miR-148a-3p, all of which have effects to regulate glucose homeostasis and insulin signaling. At the same time, insulin caused 36 miRNAs to be retained. These effects were largely independent of change in the cellular level of these miRNAs but depended on A/U-rich or poly-G motifs. Analysis of phosphoproteomic data of insulin-stimulated 3T3-L1 cells, revealed 26 RNA binding proteins known to bind A/U-rich or poly-G motifs and whose phosphorylation was altered by insulin, including hnRNPA1, FUS and KHSRP, some of which were phosphorylated at residues within their RNA-binding domains. By direct co-precipitation, we showed that hnRNPA1 binds miR-103-3p in an insulin- and motif-dependent manner, such that a 2-nucleotide mutation in the A/U motif of miR-103-3p abolished insulin-induced binding to hnRNPA1 and reduced insulin-induced secretion of miR-103-3p. Thus, insulin can regulate the secretion of exosomal miRNAs from adipocytes, which in turn can regulate metabolism in other tissues, adding a new layer to the endocrine regulation of metabolism.

Disclosure
M. Lino: None. R. Garcia Martin: None. V. Muñoz: None. B.B. Brandao: Employee; Novo Nordisk. C. Kahn: Consultant; Cellarity. Other Relationship; 1825 Therapeutics. Advisory Panel; TIXiMED, Senseion, ERX.
433-P: Status of Type 2 Diabetes among Young Adults in Community Health Centers
Authors: DELACEY SEAN E. , OWEN ANDREW L. , LAM EMILY L. , DAVIS KA'DERRICKA , EGGLESTON ALICE , WALTER EVE , O'BRIEN MATTHEW J. , WALLIA AMISHA 
Published: June 2024

Early onset Type 2 Diabetes (T2D) is characterized by earlier complications, but little is known about DM care in young adults with T2D in community health centers (CHCs). Using electronic health record data from a national CHC network, we examined sociodemographic characteristics, care patterns (i.e. medications, technology use), glycemic control and complications among young adults with T2D. We used logistic regression to identify factors associated with newer cardiovascular-DM medication use and complications. The cohort included 9,604 patients, 18-39 years, seen 1/3/2008-8/2/2023: 53% Hispanic, 26% Black (Table 1). Use of newer medications and insulin were as follows: GLP-1: 17%, SGLT-2: 12%, Insulin: 38%. Rates of microvascular or macrovascular complications were high both in those 18-29 (11% and 9%) and 30-39 years old (16% and 11%). Newer agent prescriptions (GLP-1 or SGLT-2) were less common among Hispanic and Black patients than Non-Hispanic and White patients [OR 0.84, (CI 0.73-0.96, p =0.01) and OR 0.66, (CI 0.56, 0.77, p &lt; 0.001), respectively]. Hispanic patients also had higher odds of complications (microvascular or macrovascular) than Non-Hispanic patients [OR 1.23 (CI 1.08, 1.42), p=0.003]. Complications are common among young adults with T2D, yet prescription of novel agents is low. These findings highlight the translation gap in care for young adults with T2D and the need to understand drivers of care inequities.

Disclosure
S.E. DeLacey: None. A.L. Owen: None. E.L. Lam: None. K. Davis: None. A. Eggleston: None. E. Walter: None. M.J. O'Brien: None. A. Wallia: Research Support; UnitedHealth Group, Novo Nordisk.

Funding
Chicago Center for Diabetes Translation Research (NIDDK P30 DK092949 and 5P30DK020541-47)
44-OR: Cell Intrinsic Alterations in miRNA Expression and Secretion in Muscle in Type 2 Diabetes
Authors: NAWAZ ALLAH , LINO MARSEL , GATTU ARIJEET , HAIDER NIDA , RONALD KAHN C. 
Published: June 2024

MicroRNAs are important regulators of metabolism in health and disease, and alterations in miRNAs can impact key metabolic pathways/processes, including insulin signaling, beta cell function, and fat/liver function. miRNAs are also secreted from cells in exosomes or small extracellular vesicles (sEVs) which can be taken up and regulate gene/protein expression in cells at a distance. To determine how T2D can modify the expression of cellular and sEV-secreted miRNAs, we have used a disease-in-a-dish model in which iPS cells from T2D patients and controls were differentiated into myoblasts (iMyos), and cellular and secreted sEV miRNAs assessed using a nuclease protection assay, which assesses all known human miRNAs. We show that, compared to controls, iMyos from T2D in vitro exhibit significant alterations in cellular expression of 71 miRNAs, with 22 up-regulated and 49 down-regulated. Overlapping the predicted miRNA-targets of the up-regulated miRNAs with global proteomics data revealed 123 proteins that were targeted and down-regulated by these miRNAs, consistent with the fact that a single miRNA has multiple targets and indicating that T2D-induced alterations in miRNA expression contribute to broad range of changes in cellular protein. In the sEVs secreted from iMyo, there were even more marked changes, with 70 up- and 296 down-regulated miRNAs, demonstrating a major alteration in regulation of miRNA secretion by muscle in T2D. Importantly, most of the T2D-regulated sEV are known to be involved in the development of insulin resistance and T2D. For example, levels of miR-1299, miR-1324, and miR-378h were elevated in T2D-derived sEVs, and we show that these miRNAs can suppress gene expression of PTEN, PGC-1α/β and FASN in adipose tissue. The dysregulated miRNA expression and secretion contribute to altered gene/protein expression in the myoblast itself, as well as targeting metabolic and signaling genes in other tissues, such as adipose tissue, thereby contributing to the pathogenesis of T2D.

Disclosure
A. Nawaz: None. M. Lino: None. A. Gattu: None. N. Haider: None. C. Kahn: Consultant; Cellarity. Other Relationship; 1825 Therapeutics. Advisory Panel; TIXiMED, Senseion, ERX.