bluuebunny/crossref_metadata_2025 huggingface dataset:
32-OR: First Impact on A1C of Medically Underserved Patients with Type 2 Diabetes Using a Hybrid Chronic Care Model
Authors: LEE JOYCE Y. , SEO MINJONG , NGUYEN JENNY T. , RODRIGUEZ ALLEN , RODRIGUEZ VANESSA , CHAN ALEXANDRE , MAYORGA JOSE
Published: June 2024

Timely access to care is crucial for effective diabetes management, but social determinants of health often present significant obstacles. A hybrid chronic care model (h-CCM), which combines pharmacist-conducted telemedicine visits with in-person provider visits, was established to minimize health disparities through enhanced options for healthcare delivery. This study was designed to compare the first A1C changes among medically underserved patients with T2D who received diabetes care from h-CCM versus usual care. This was a prospective intervention study conducted at a FQHC located in Southern California between Oct 2021 and Dec 2022. Patients ≥ 40 years with T2D who received h-CCM (intervention) were compared to the control or usual care which included in-person provider visits only. The control data were generated from UCI Data Warehouse (UCI IRB#2636), matched 1:1 by age, gender, ethnicity, and baseline A1C of the intervention arm during the same time period. Descriptive statistics and Student’s t-test were utilized to compare the demographics and clinical characteristics between the two arms. A total of 208 patients (I: 104, C: 104) were included in the analysis. The average age for both arms was 61.0 SD ±10.5 years with majority being female (57.7%) and Latinx (70%), and a mean A1C of 9.4 ±1.5%. The mean baseline 10-year ASCVD score (%) was comparable (I:19.6 ±16.6 vs. C:22.6 ±17.2; p=0.202). At 3 months, the A1C for the intervention and control arms were 8.74 ±1.89% and 9.41 ±0.12%, respectively, with an average A1C reduction of 0.7% (95% CI: 0.3-1.0, p <0.001%) observed in the intervention arm and no change in the control. A minimal mean (±SD) % reduction for the ASCVD score was observed in the intervention arm (-0.6 ±5.5) with worsening trend observed in the control (0.2 ±1.9).

In conclusion, h-CCM appeared to effect a quicker improvement in A1c during the first three months of care implementation when compared to usual care in medically underserved patients.

Disclosure

J.Y. Lee: None. M. Seo: None. J.T. Nguyen: None. A. Rodriguez: None. V. Rodriguez: None. A. Chan: None. J. Mayorga: None.
354-OR: The Role of Clic-Like Chloride Channel 1 in the Pancreatic Beta Cell
Authors: ZHANG YAOHUAN , YIV NICHOLAS , SHARIATI KAAVIAN , SANFILIPPO ANDREW , KU GREGORY M.
Published: June 2024

Chloride is one of the most abundant electrolytes and has many important physiological functions. Though it is known that chloride plays a role in beta cell physiology and insulin secretion, intracellular chloride fluxes and how they affect beta cell development and function are relatively poorly understood. Clic-like chloride channel 1 (Clcc1) is an endoplasmic reticulum (ER) localized chloride channel whose loss causes ER stress and cell death in neurons and retinal cells. We found that Clcc1 beta cell specific knockout (Clcc1 beta-KO) mice were glucose intolerant with lower plasma insulin and pancreatic insulin content at 10 weeks of age. We found that fewer Clcc1 beta-KO mouse beta cells were dividing at 21 days of age, suggesting reduced neonatal beta cell expansion. Beta cell area was reduced by 50% at 10 weeks of age, but surprisingly, we found a 95% reduction in islets that could be isolated by traditional collagenase digestion of the pancreas, suggesting that adult Clcc1 beta-KO mouse islets were structurally altered. This islet fragility was age dependent; normal numbers of islets could be isolated from Clcc1 beta-KO mice up to 14 days of life. These islets had normal glucose stimulated insulin secretion but had 50% less insulin content compared. Single cell RNA-sequencing showed fewer proliferating beta cells but no obvious unfolded protein response. Our data shows that Clcc1 has a surprising role in islet structure, insulin production and beta cell growth. Our research is currently focused on understanding the effect of loss of Clcc1 on ER chloride flux and the mechanism of how that might affect islet structure, beta cell function, and growth.

Disclosure

Y. Zhang: None. N. Yiv: None. K. Shariati: None. A. Sanfilippo: None. G.M. Ku: None.

Funding

National Institutes of Health (TR004204); National Institutes of Health (DK1249040; Sandler Program for Breakthrough Biomedical Research UCSF
360-OR: Defining New Targets for Interventions to Increase Continuous Glucose Monitoring (CGM) Use in Primary Care
Authors: MILOSAVLJEVIC JOVAN , MATHIAS PRIYANKA M. , SCHECHTER CLYDE , AGARWAL SHIVANI
Published: June 2024

Background: CGM is a standard of care for diabetes management, yet its adoption in primary care remains limited where the majority of people with diabetes are served. Examining contributors to CGM prescriptions in primary care may identify new targets for intervention that could improve diabetes population health.

Methods: We examined CGM prescription behaviors of primary care providers within a large safety net hospital in the Bronx, NY. We extracted data from the electronic health record on all adults ≥18 years with type 2 diabetes and at least one primary care visit from July 31, 2020, to July 31, 2023. We used competing risk regression to model factors associated with CGM prescription.

Results: Out of 40,791 people with type 2 diabetes (mean age 62 years, 60% female, 39% Hispanic, 39% Non-Hispanic Black, 77% English-speaking, 47% publicly insured, 27% seen by trainee physicians), 4,129 (10.1%) were prescribed CGM. CGM was 40% less likely to be prescribed for Spanish vs. English-speaking (SHR 0.60 [0.54-0.68]), 15% less likely with public insurance (SHR 0.85 [0.79-0.91]), and 25% less likely with diabetes complications (microvascular SHR 0.73 [0.67-0.79], macrovascular SHR 0.77, [0.69-0.86]). Conversely, CGM was 30% more likely to be prescribed with each additional HbA1c percentage point (SHR 1.31 [1.30-1.34]) and 6% more likely with each additional prescriber year of experience (SHR 1.06, [1.05-1.07]). CGM prescriptions increased in a dose-response manner with treatment intensification (non-insulin SHR 2.08 [1.76, 2.46]; basal insulin SHR 3.94 [3.27-4.75]; multiple daily insulin SHR 5.03 [4.17-6.07]).

Conclusion: Our analysis of a large primary care network of people with diabetes can inform strategies to support more widespread CGM use in primary care. New targets could include Spanish language support services; aid for better prior authorization procedures for public insurance; and increased education of CGM benefits for providers with less years of experience.

Disclosure

J. Milosavljevic: None. P.M. Mathias: None. C. Schechter: None. S. Agarwal: Research Support; Dexcom, Inc. Advisory Panel; Medtronic. Consultant; Beta Bionics, Inc.
365-OR: Maladaptive Sensory Plasticity via α2δ1-subunit Promotes Adipose Tissue Lipolysis after Spinal Cord Injury
Authors: ROY DEBASISH , DION ELLIOT G. , SEPEDA JESSE A. , PENG JUAN , TOWNSEND KRISTY L. , SAS ANDREW , SUN WENJING , TEDESCHI ANDREA
Published: June 2024

Spinal cord injury (SCI) leads to a progressive decline in metabolic homeostasis. Thus far, it is unclear whether the underlying cause of metabolic complications after SCI may be linked to the dysregulation of adipose tissue. The sympathetic nervous system and sensory neurons with cell bodies located in the dorsal root ganglia (DRG) innervate white adipose tissue (WAT). However, the extent to which sensory innervation drives WAT function under normal and pathophysiological conditions has remained elusive. To investigate structural changes in WAT, we subjected adult mice to a thoracic (T)12 SCI that completely transected sensory axons without impacting sympathetic nerve activity. Whereas no changes were observed in iWAT, we found an increase in the percentage of small-size adipocytes in eWAT, a phenotype associated with rapid lipid partitioning. Our biochemical and molecular analysis confirmed that SCI exacerbates lipolysis in eWAT but not in iWAT. After injury, maladaptive reorganization of neuronal circuits can cause aberrant neuron firing that eventually culminates in the onset of post-traumatic disorders. We and others have demonstrated a strong convergence between the rearrangement of neuronal circuits and the expression of α2δ subunits of VGCC. α2δ subunits positively regulate neurotransmitter release by increasing plasma membrane expression of VGCC. We discovered that α2δ1 expression increases in CGRP+ DRG neurons that project to eWAT 7 days after SCI. Conditional deletion of the gene encoding α2δ1 in these neurons normalizes eWAT lipolysis after SCI. Using a clinically relevant strategy, we demonstrated that α2δ1 pharmacological blockade also normalizes eWAT lipolysis after SCI, thereby preventing ectopic lipid accumulation in the liver. Thus, our study provides novel insight into the molecular basis of maladaptive sensory processing in eWAT, facilitating the development of strategies to promote metabolic health after SCI.

Disclosure

D. Roy: None. E.G. Dion: None. J.A. Sepeda: None. J. Peng: None. K.L. Townsend: None. A. Sas: None. W. Sun: None. A. Tedeschi: None.

Funding

National Institute of Neurological Disorders and Stroke (R01NS110681), National Institute of Health (P30CA016058)
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<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 (<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<0.0001) and HDL (women: r= -0.42, P<.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<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<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 < 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.
442-P: Diabetic Foot Ulcer Amputation Is Associated with Two-Fold Increased Risk of Incident Cardiovascular Disease—A Korean National Health Information Database Study
Authors: YANG HYEWON , KIM BONGSEONG , JANG JINSUN , SON HEEJUN , SEUNG JUNG HYE , MIN CHO YOUNG , SOO PARK KYONG , HAN KYUNGDO , HEON KWAK SOO
Published: June 2024

Diabetic Foot Ulcer (DFU), a critical complication of diabetes, impacts about 8% of individuals with diabetes and leads to a 20% risk of lower extremity amputation. People with DFU amputation are widely recognized to have an increased risk of cardiovascular disease (CVD) and mortality. However, previous studies have been limited by their small scale and cross-sectional design. The aim of this study was to quantify the risk of CVD and related mortality following DFU amputation, utilizing a large-scale prospective database.We included over 1.2 million individuals with diabetes who participated in nationwide health checkups from 2009 to 2012, with clams data linked through the Korean National Health Insurance Service. Incident CVD was defined as myocardial infarction (MI), stroke and cardiovascular mortality that occurred at least one year after a DFU amputation. Cox proportional hazard model was used to assess the risk of CVD in people with DFU amputation compared to those with diabetes but not amputated. Among 1,229,689 individuals with diabetes, 1,487 (0.12%) had a DFU amputation at baseline. Individuals with DFU tended to be older, predominantly male, and more often belong to the lower income 10%. During a median follow-up of 7.2 years (interquartile range 3.08), people with DFU amputation had a significantly higher incidence rate of CVD compared to those without DFU amputation (32.6 vs 11.0 per 1,000 person-years) with a hazard ratio (HR) of 1.8 (95% CI 1.6-2.1). Specifically, the HRs for MI and stroke were 2.2 (95% CI 1.9-2.6) and 1.6 (95% CI 1.4-1.8). Furthermore, CVD mortality significantly increased in people with DFU amputation compared to those without, with an HR of 2.11. (95% CI 1.9-2.3).Using a comprehensive nationwide health information database, we found that individuals with DFU amputation had up to a two-fold higher risk of CVD and associated mortality compared to those with diabetes but without DFU.

Disclosure

H. Yang: None. B. Kim: None. J. Jang: None. H. Son: None. H. Jung: Research Support; Novo Nordisk. Y. Cho: None. K. Park: None. K. Han: None. S. Kwak: Employee; SNUH Venture.

Funding

Funds of National Health Insurance Service and Korean Diabetes Association (2023-285)
446-P: Prognostic Role of Type 2 Diabetes Mellitus in Minor vs. Major Atherosclerosis
Authors: MADER ARTHUR , HAEBERLI DARIO , LARCHER BARBARA , DOPHEIDE JOERN F. , PLATTNER THOMAS , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , HEINZLE CHRISTINE , AMANN PETER , SCHINDEWOLF MARC , SAELY CHRISTOPH H. , DREXEL HEINZ
Published: June 2024

The impact of diabetes on major cardiovascular events (MACE) in relation to the extent of pre-existing atherosclerotic disease remains unclear. In this study we compare the impact of T2DM on MACE in patients with two different states of atherosclerosis: minor coronary atherosclerosis (minAS) and peripheral artery disease, one of the most severe manifestations of major atherosclerosis (majAS). We included 1238 patients from two long-term prospective cohort studies. Patients underwent coronary angiography for the allocation to a control group without any lumen irregularities (n=332) or a minAS group with lumen irregularities but no significant coronary stenoses ≥50% at coronary angiography (n=425). Patients with sonographically proven peripheral artery disease were allocated to the majAS group (n= 481). Over a mean time-period of 7.7 years major cardiovascular events (MACE) were recorded. Overall, MACE were recorded in 681 (51%) patients. T2DM significantly increased the risk of MACE both among patients with minAS (22.0% vs. 32.4%; p=0.023) and majAS (50.6% vs. 67.1%; p<0.001) but nut in the control group (12.0% vs. 12.1%; p=0.663). In majAS - patients who did not have T2DM, the risk of MACE was higher than that of T2DM patients with minAS (p<0.001). Both T2DM (adjusted HR=1.78 [1.45-2.17], p<0.001) and severity of atherosclerosis (adjusted HR=2.59 [2.18-3.10], p<0.001) predicted MACE in a mutually independent manner. An interaction term severity of atherosclerosis x T2DM was not significant (p=0.364), indicating that the severity of pre-existing atherosclerosis did not impact the power of T2DM as a predictor of MACE. We conclude that T2DM confers an increased risk for MACE both in early and in advanced atherosclerotic states. The severity of pre-existing atherosclerosis does not impact the power of T2DM as a predictor of MACE.

Disclosure

A. Mader: None. D. Haeberli: None. B. Larcher: None. J.F. Dopheide: None. T. Plattner: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. C. Heinzle: None. P. Amann: None. M. Schindewolf: None. C.H. Saely: None. H. Drexel: None.
453-P: Remnant Cholesterol Predicts Major Cardiovascular Events in Coronary Artery Disease Patients with NAFLD
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study. We enrolled a high-risk cohort of 913 patients with coronary artery disease (CAD). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.5±5.2 years. At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=419) than in patients who did not have NAFLD (30±28 mg/dl vs. 18±17 mg/dl; p<0.001). During follow-up, 379 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.18 [1.08-1.30], p<0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.19 [1.05-1.35], p=0.006 and 1.24 [1.03-1.49], p=0.023, respectively). From our data we conclude that remnant cholesterol is a predictor of MACE in patients with CAD with and without NAFLD.

Disclosure

T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
46-PUB: A Quantitative Framework for Evaluating the Performance of Whole-Population Remote Patient Monitoring for Type 1 Diabetes Care
Authors: KURTZIG JAMIE , SCHEINKER DAVID
Published: June 2024

Introduction: Care providers continue to adopt platforms that enable remote patient monitoring (RPM) for type 1 diabetes (T1D) care through the algorithmic analysis of continuous glucose monitor (CGM) data. No provider-facing quantitative framework is available to track how the use of such platforms impacts patient care and healthcare provider workload. We propose such a framework.

Methods: We used data from four sub-studies (n=127, 137, 136, 95) of whole-population algorithm-enabled RPM for T1D in Stanford’s pediatric Teamwork, Targets, Technology, and Tight Control (4T) Study. We used HbA1c measurements, CGM data, time studies of care providers, and secure messages sent by care providers to patients and families. We iteratively analyzed data and interviewed care providers to identify metrics relevant to whole-clinic and whole-population patient care and healthcare provider workloads. We developed an interactive dashboard to facilitate monitoring these metrics.

Results: The metrics identified were: the numbers of patients (1) in the overall program, (2) in each sub-study, (3) cared for by each care provider, (4) meeting criteria for review or care in each clinical category, (5) in each clinical category by care provider, (6) in each clinical review category by sub-study, and (7) each patient’s most recent date of being eligible for review by care providers.

Conclusion: We propose the first quantitative framework for healthcare organizations to supervise and enhance algorithm-enabled whole-population T1D care. As the role of digital care platforms continues to increase, this framework may help clinics manage and improve their programs.

Disclosure

J. Kurtzig: None. D. Scheinker: None.
462-P: Medication Documentation in Patients with Type 2 Diabetes Undergoing Coronary Angiography
Authors: ELSNER PASCAL , RATZ MAGDALENA , VOGEL JOHANNES , SAELY CHRISTOPH H. , PLATTNER THOMAS , MADER ARTHUR , LARCHER BARBARA , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ
Published: June 2024

The utilization of multiple medications and the increasing complexity of medication regimens associated with chronic diseases such as type 2 diabetes (T2DM) necessitate the implementation of a medication documentation (MD). A complete medication plan serves to enhance medication safety and promotes adherence. The availability of MD in the clinically important population of T2DM patients undergoing coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD) remains unknown and is addressed in the present study. We analyzed MD, current medication status, and the Medication Regimen Complexity Index (MRCI) in 515 consecutive patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Our cohort included 177 patients (34%) with T2DM and 338 patients (66%) without diabetes. Patients with T2DM compared to those without diabetes had a significantly higher number of medications (7 [5-9] vs. 5 [3-6]; p<0.001) and a significantly higher complexity in medication regimens (17 [11-24] vs. 12 [7-16]; p<0.001). Specifically, out of 104 (59%) T2DM patients, MD was available, while 73 (41%) lacked MD. Further classification showed the following categories of MD in patients with diabetes: unstructured documentation in 28 (27%), physician’s letter in 17 (16%), medication plan in 58 (56%) and other categories in 1 (1%). We conclude that patients with T2DM who undergo coronary angiography for the evaluation of established or suspected stable CAD are affected by a high medication complexity and polypharmacy, which highlights the importance of an accurate MD in these patients. However, proper MD is not available in almost half of these patients.

Disclosure

P. Elsner: None. M. Ratz: None. J. Vogel: None. C.H. Saely: None. T. Plattner: None. A. Mader: None. B. Larcher: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
466-P: Therapeutic Efficacy of Monthly Semaglutide-Loaded Microsphere Injections in Zucker Diabetic Fatty Rats
Authors: PARK JIWON , KIM CHERNGJU , AN TAEKUN
Published: June 2024

Introduction: This study aimed to develop semaglutide-loaded microsphere monthly injectables using a novel biodegradable microsphere manufacturing technology, and to compare its therapeutic efficacy with both semaglutide solution, administered weekly injectables, and semaglutide microsphere, administered monthly injectables, in male Zucker diabetic fatty (ZDF) rats and ZDF lean control rats.

Methods: Semaglutide microsphere was prepared by water-in-oil-in-water (w/o/w) emulsion solvent evaporation method using poly(D, L-lactide-co-glycolide) (PLGA). Therapeutic efficacy was evaluated by measuring blood glucose in both Zucker diabetic fatty (ZDF) and ZDF lean control rats. Subcutaneous administrations were performed once for the Semaglutide microsphere and vehicle control groups, while the Semaglutide solution was administered four times at weekly intervals.

Results: The Semaglutide microsphere significantly decreased blood glucose concentration compared to both the vehicle and semaglutide solution groups for four weeks, resembling levels in the lean control group (100 mg/dL) (Figure 1).

Conclusion: The Semaglutide microsphere injectables, administered monthly, showed the potential to substantially reduce the frequency of administrations compared to the commercial product, Ozempic® and Wegovy®, thereby potentially enhancing patient compliance.

Disclosure

J. Park: None. C. Kim: None. T. An: None.
467-P: Type 2 Diabetes and Chronic Kidney Disease as Predictors of Cardiovascular Events in Patients with Coronary Artery Disease
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

This study aims to investigate the single and joint effects of T2DM and CKD on cardiovascular events in patients with coronary artery disease (CAD). We prospectively investigated 1044 patients with CAD over 8.5±5.0 years. Cardiovascular events occurred more frequently in T2DM patients (n=347) than in nondiabetic subjects (60.1% vs 50.6%, p=0.004) and in patients with CKD (eGFR<60ml/min/1.73m2; n=192) than in those without CKD (64.7% vs 51.2%, p<0.001). When both T2DM and CKD were considered, 586 subjects had neither T2DM nor CKD, 266 had T2DM but not CKD, 111 did not have diabetes but had CKD, and 81 had T2DM and CKD. Compared to the incidence of cardiovascular events among patients with neither T2DM nor CKD (49.6%), cardiovascular events were not significantly increased in patients with T2DM who did not have CKD (54.9%; p=0.121) or in nondiabetic patients with CKD (55.9%; p=0.298); however, the incidence of cardiovascular events was significantly increased in patients with the combination of T2DM and CKD (77.2%; p<0.001), in whom it was higher than in those with T2DM but not CKD (p<0.001) or those without T2DM but with CKD (p=0.001). In Cox regression analysis, T2DM (HR 1.31 [1.09-1.57]; p=0.004) and CKD (HR 1.32 [1.05-1.64]; p=0.016) proved to be mutually independent predictors of cardiovascular events after multivariate adjustment for age, sex, BMI, history of smoking, hypertension, LDL-C and HDL-C. We conclude that T2DM and CKD in patients with CAD are mutually independent predictors of cardiovascular events. CAD patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.

Disclosure

T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
468-P: Association between Sudomotor Function and Coronary Atherosclerosis in Patients with Type 2 Diabetes
Authors: XU HUAN , CHEN XUEYAN , PENG JIE , TANG XIAOYUN , SHUI XING , YAN JINHUA , XU WEN , YAO BIN , DENG HONGRONG , YANG XUBIN
Published: June 2024

Object: This study aims to investigate the relationship between sudomotor function and coronary atherosclerosis in patients with type 2 diabetes.

Methods: A total of 147 patients with type 2 diabetes were enrolled (64.60% male, 59.58±10.20 years). Using sudoscan detector to assess the mean electrochemical skin conductance (ESC). Patients were divided into three groups according to the mean hands and feet ESC: sudomotor severe dysfunction group (SDF: ESC < 40μS), sudomotor moderate dysfunction group (MDF: 40μS ≤ ESC ≤60μS) and normal sudomotor function group (NSF: ESC > 60μS). The severity of coronary atherosclerosis was determined according to Gensini score.

Results: Gensini score was significantly different among the three groups, with an increasing trend from NSF to MDF and SDF[3.50(0.00, 12.00) vs. 6.50(2.13, 12.25) vs. 10.50(4.86, 22.75), P=0.010]. Spearman correlation analysis revealed a negative correlation between the Gensini score and hand ESC (r=-0.2, P=0.013). After adjusting for confounding factors, multiple linear regression analysis indicated that ESC was significantly associated with coronary atherosclerosis (OR=0.100, 95% CI: 0.012-0.875, P=0.038).

Conclusions: In patients with type 2 diabetes, the severity of coronary atherosclerosis increased with impaired sudomotor function, and sudomotor dysfunction is independently associated with coronary atherosclerosis.

Disclosure

H. Xu: None. X. Chen: None. J. Peng: None. X. Tang: None. X. Shui: None. J. Yan: None. W. Xu: None. B. Yao: None. H. Deng: None. X. Yang: None.

Funding

Natural Science Foundation of Guangdong Province (2018A030313915); Medical Scientific Research Foundation of Guangdong Province of China (A2018286).