bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP235 Quality Improvement Survey to Identify Barriers to Oral Glucose Tolerance Test in Patients with Cystic Fibrosis
Authors: Trevino Alexandra , Afshariyamchlou Sonia , Khare Swapnil 
Published: November 2022

Abstract

Background
Cystic Fibrosis (CF) is the most common autosomal recessive disorder in Caucasians and can involve multiple organ systems. Cystic Fibrosis Related Diabetes (CFRD) is the most common complication which affects at least 40-50% of the adult patients with CF. Untreated CFRD adversely affects pulmonary function, nutritional status, and is associated with overall poor outcomes. Early diagnosis and treatment with insulin improve nutritional status, pulmonary function and is associated with reduced mortality. An annual two-hour Oral Glucose Tolerance Test (OGTT) is recommended for all patients with CF beginning at 10 years of age. Unfortunately, OGTT screening rates remain very low in patients with CF. The aim of this study was to identify patient barriers to OGTT screening and list them in order of relative importance from patient perspective.

Methods
A survey was designed to identify patient barriers associated with completing the screening OGTT in the CF population. Data collection included patient demographics and pertinent clinical information. All patients &gt;18 years of age and who receive care at the Cystic Fibrosis center at our institute received a survey. Survey was sent through email, postal mail, or during CF center visits. Patients who did not initially complete survey received a reminder email, phone call, and hand survey during CF appointment. Participants were excluded if they had a diagnosis of CFRD or were currently pregnant. There was no intervention planned during this study.

Results
49 patients without CFRD and 19 patients with CFRD responded to survey. Only 12.2% patients were appropriately screened by OGTT in last 1 year. The survey demonstrated that the top 3 barriers to obtaining OGTT in descending order were "I don't think I have diabetes, I don't need this"; "I don't like the taste of glucola"; and "I don't think OGTT is important for assessing my health".

Conclusions
The prevalence of CFRD continues to increase as the median life expectancy increases in patients with CF and is associated with worse outcomes. Early diagnosis and treatment with insulin are crucial. Unfortunately, screening for CFRD remains low in this population. Our study highlights the patient perceived barriers for screening OGTT. The top 3 barriers noted in study show the importance of patient education and awareness about CFRD. Further research is needed to identify specific interventions that will improve CFRD screening and lead to earlier diagnosis and treatment.
Presentation: No date and time listed
ODP251 Thioredoxin-Interacting Protein (Txnip) And Cellular Senescence: Potential Adverse Effects of Txnip Deficiency.
Authors: Abubaker Mohammed , Fantus George I 
Published: November 2022

Abstract
Thioredoxin-interacting protein (TXNIP) is a ubiquitously expressed protein that belongs to the α-arrestin family of proteins but is unique in that it interacts with and inhibits the function of the endogenous antioxidant, Thioredoxin (Trx). TXNIP is strongly upregulated by hyperglycemia and is associated with increased oxidative stress and promotes pancreatic beta cell apoptosis accelerating the progression of diabetes. Age-dependent dysregulation of the Trx/TXNIP redox system has been implicated in cellular senescence and aging. However, the mechanisms are not fully understood. While Trx overexpression has been reported to protect against aging and age-related diseases, and we found that TXNIP-/- (KO) mice were protected from Diabetic kidney disease, paradoxically, others reported TXNIP KO mice had reduced survival in response to paraquat mediated oxidative stress. To investigate the potential effects of TXNIP in cellular senescence we used primary mouse renal glomerular mesangial cells (MC) from WT and TXNIP KO mice. Passaging of cells leads to replicative senescence. In WT MC this was associated with a significant reduction in TXNIP expression in late passage (LP-passage 25) compared to early passage (EP-passage 5-7) (p&lt;0. 05), and this was accompanied by appearance of the senescence phenotype determined by significant increases in expression of the cellular senescence markers, p53, p16, p21, phosphorylation of histone H2AX (p&lt;0. 05) and senescence associated beta-galactosidase staining (13-fold increase) (p&lt;0. 01). To determine whether TXNIP downregulation played a causal role, primary MC from TXNIP KO were compared to WT at EP 5. TXNIP KO showed significantly higher expression of senescence markers P53 and P16 (p&lt;0. 05), and beta-galactosidase staining (15-fold). AKT activation has been implicated in replicative senescence. Here, increased phosphorylation of AKT and its substrate FOXO were found in LP versus EP WT, and EP KO versus WT MC (p&lt;0. 05). These studies indicate that TXNIP downregulation is a mediator of replicative senescence associated with increased AKT signaling. Thus, while beneficial for diabetes, targeting TXNIP may have long term untoward effects on aging.
Presentation: No date and time listed
ODP252 Urosepsis and Sodium-Glucose Co-Transporter-2 Inhibitors: A Systematic Review and Meta-Analysis
Authors: Prasongdee Klaorat , Toloza Freddy J , Fernandes Talmas P , Poloju Alekya , Lopez-Saldana Rigoberto , Lock John P 
Published: November 2022

Abstract

Objective
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are very effective in reducing hemoglobin A1c. They also have benefits in reducing cardiovascular events, heart failure hospitalization, and progression of renal disease in patients with and without T2DM. However, FDA issued a warning for a possible severe UTI. Conversely, the evidence from randomized clinical trials and observational studies is limited and controversial. Therefore, we aimed to investigate the association of urosepsis and SGLT-2 inhibitors using the method of systematic review and meta-analysis.

Methods
Potentially eligible studies were identified from MEDLINE, Scopus, EMBASE, Ovid, and the Cochrane Library from inception to September 2020 with the help of an experienced librarian aiming to identify studies reporting the number of adults users of any SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin, and tofogliflozin) who developed urosepsis, compared to those who never used SGLT2 inhibitors. The following exclusion criteria were used: only abstracts or pilot data, studies reporting rates of urosepsis only in SGLT2 inhibitors users without comparison, or studies with a comparison group in which SGLT2 was not the only differential treatment.

Results
In total, 1203 papers were identified with our search strategies, of which 169 were evaluated as full text, and 6 studies were finally selected for the meta-analysis after two rounds of the independent review by five investigators. The overall risk of bias of the included studies was low-to-moderate. We found no difference in the risk of urosepsis in users of SGLT2 inhibitors (OR= 1.34; 95% CI, 0.79 to 2.28; P=0.28; I2=48%) compared to the comparison group. In a subgroup analysis by the type of SGLT2 inhibitor evaluated we found no differences between dapagliflozin (OR= 0.92; 95% CI, 0.51 to 1.67; P=0.82; I2=0%) or canagliflozin (OR= 0.32; 95% CI, 0. 03 to 3.63; P=0.27; I2=17%) users in the risk of urosepsis. Publication bias was assessed by performing funnel plots which showed visual asymmetry suggestion potential publication bias.

Discussion/Conclusion
In this systematic review and meta-analysis, including 6 publications and 456301 participants, we found that individuals treated with SGLT2 inhibitors do not have a significantly higher risk of urosepsis than individuals of the comparison group. Additionally, no differences were found in the risk of urosepsis when each SLGT2 inhibitor agent was assessed separately.
Presentation: No date and time listed
ODP259 Evaluating the Efficacy and Safety of Long-Acting GLP-1 Receptor Agonist in T1DM Patients
Authors: Mohandas Deene , Gao Catherine , Calma Jamie , Basina Marina 
Published: November 2022

Abstract

Introduction
GLP-1 receptor agonist is a medication class that mimics the endogenous incretin hormone GLP-1. Short-acting GLP-1 agents were studied as adjunct therapies in type 1 diabetes (T1DM) but not approved due to concern of increased diabetic ketoacidosis (DKA) risk. Long-acting GLP-1 medications are still commonly prescribed for T1DM patients. One study has assessed the impact of a long-acting GLP-1 in 11 T1DM patients. No hospitalizations were observed, and time in range was not reported. [1] Our study aims to evaluate the efficacy and safety of long-acting GLP-1 medications in a larger cohort of T1DM patients.

Methodology
We conducted a retrospective chart review of T1DM patients taking a long-acting GLP-1 for at least three months. ICD-10 code E10. Type 1 diabetes mellitus was used to search our institution's Electronic Health Record system (EPIC). Primary parameters collected included A1C and glycemic trends. Data analysis was done by averaging values over a two-year period before and after starting the medication.

Results
We identified 27 participants with T1DM (mean age 42yrs, mean T1DM duration 18.1yrs) on a long-acting GLP-1 (semaglutide 70.4%, dulaglutide 33.3%, long-acting exenatide 3.7%, albiglutide 3.7%). Mean therapy duration was 24.28±19. 01mo. A1C values decreased significantly from7.61±1. 08% to 7.16±0.73% (p=0. 015, N=25). Per CGM data, average time in range (TIR) increased significantly from48.82±22.35% to64.70±16.58% (p=0. 0002, N=15), average time in hyperglycemia decreased from42.39±23.32% to 31.58±16.65% (p=0. 019, N=14) and 14-day blood mean glucose decreased from 190.40±38.42 mg/dl to 167. 06±25.86 mg/dl (p=0. 001, N=17). There were no statistically significant differences in time in hypoglycemia and incidence of DKA. Hyperglycemic and hypoglycemic episodes were defined per patients’ individualized CGM settings (most commonly Blood Glucose levels&gt;180 and &lt;70 respectively). Patients’ weight decreased non-significantly from182. 00±50.92 lbs to 170.88±51.37 lbs (p=0.128, N=8). There were no ER visits or hospitalizations for DKA while on GLP-1 therapy.

Conclusion
There is an urgent need for strategies to improve glycemic control and reduce morbidity and mortality in T1DM. Long-acting GLP-1s are a promising adjunct to insulin. Our study is the first to demonstrate significant A1C reduction and TIR increase without increased hypoglycemia and DKA risk in 27 T1DM patients on long-acting GLP-1s. Longer prospective studies are warranted.
Presentation: No date and time listed
ODP623 Life Threatening Diabetic Ketoacidosis as First Presentation of Tacrolimus-Induced Diabetes Mellitus.
Authors: Bulchandani Sheetal , Goyal Rachna M 
Published: November 2022

Abstract

Background
New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients.1 Tacrolimus is an immunosuppressive agent associated with diabetogenic potential which predominantly is a result of suppression of insulin secretion from pancreatic beta cells. Diabetic ketoacidosis as the first presentation of new onset tacrolimus induced diabetes is rare. We report a case of diabetic ketoacidosis (DKA) in a patient without prior history of diabetes mellitus and receiving tacrolimus as part of immunosuppressive regime post-renal transplant.

Clinical Case
A 62-year-old female with past medical history of autosomal polycystic kidney disease status-post deceased donor renal transplant and hypertension presented with weakness and fatigue. She had undergone transplant 8 months prior to this presentation and her immunosuppressive regime consisted of mycophenolate mofetil and tacrolimus. The patient was encephalopathic on arrival with normal vitals. Laboratory evaluation was significant for blood glucose of 673, bicarbonate of &lt;10, anion gap of 24, Beta-hydroxybutyrate &gt;8 and a pH of 7.19 on arterial blood gas analysis thus confirming diagnosis of diabetic ketoacidosis (DKA). Tacrolimus level was elevated at 35.7. Intravenous fluids and insulin were initiated with resolution of symptoms and DKA. She was transitioned to a basal-bolus insulin regimen. Further labs revealed Hemoglobin A1C of 11.6% (no previous value), negative insulin antibodies and glutamic acid decarboxylase antibody, and a low C-peptide level at 0.47 (when blood glucose was 150mg/dl). Her tacrolimus dose was adjusted, and she was discharged on a basal-bolus insulin regimen. On follow up, the patient had lower insulin requirements with improvement in C-peptide level to 1.8, thus, indicating beta cell dysfunction in setting of supratherapeutic tacrolimus levels.

Conclusion
Tacrolimus remains the preferred immunosuppressive agent after kidney transplantation given lower incidence of acute rejections and better tolerance. However, due to its toxic effects on pancreatic beta cells it is imperative blood sugar levels should be routinely monitored in patients on tacrolimus. Appropriate monitoring can lead to timely diagnosis and successful outcomes. Further studies are required to investigate risks factors associated with tacrolimus induced DKA. References 1. Pham PT, Pham PM, Pham SV, Pham PT, Pham P. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011;4: 175-186, https://doi.org/10.2147/DMSO.S19027
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP628 Quality Improvement Project (QIP) On Management Of Diabetic Ketoacidosis (DKA) In Adults In A District General Hospital.
Authors: Haddad Aiman , Yanagisawa Yuuki , Khan Mustafa 
Published: November 2022

Abstract

Aim
A Quality Improvement Project was conducted to assess if Bedford Hospital NHS Foundation Trust was meeting current Trust guidelines for the diagnosis and management of diabetic ketoacidosis (DKA) in adult patients. Method Retrospective data was collected from adult patients admitted with a diagnosis of DKA from January 2020 to December 2020. Data was collected for five key standards based on Trust guidelines: (1) Correct diagnosis of DKA, (2) Correct prescription of Intravenous (IV) fluids and potassium chloride (KCL) replacement, (3) Switching from Fixed Rate Intravenous Insulin Infusion (FRIII) to Variable Rate Intravenous Insulin Infusion (VRIII) following resolution of DKA, (4) The prescription of long-acting insulin during FRIII/VRIII and (5) Appropriate biochemical monitoring via regular venous blood gases (VBGs). Following data analysis, an intervention phase (with distribution of 'DKA diagnosis and management' posters, DKA teaching sessions and email updates on DKA management for medical doctors) was implemented. The cycle was repeated a further two times, with the most recent cycle based on patients admitted between August to November 2021.

Results
The first cycle consisted of 25 patients. Results showed a 72% adherence to Standard 1, a 64% adherence to Standard 3 and a 76% adherence to Standard 5. There was a notably low adherence to Trust guidelines for Standards 2 and 5, which were 32% and 12% respectively. After the intervention phases described earlier, results from the final cycle of 20 patients admitted between August to November 2021 showed significant improvement in standards 1,3 and 4 with 90%, 100% and 100% adherence to Trust guidelines respectively. Although there was a slight improvement in biochemical monitoring of patients with regular VBGs (20% adherence in the final cycle versus 12% in the first cycle), the correct prescription of IV fluids and KCL replacement remained low (17% adherence in the final cycle versus 32%).

Conclusion
Awareness and diagnosis of DKA remains high at Bedford Hospital, however there are issues regarding the ongoing management of DKA patients. In particular, the correct prescription of IV fluids with KCL replacement, and regular biochemical monitoring. There is still a lack of awareness as to the appropriate rate of IV fluid resuscitation, and the correct monitoring and replacement of potassium, as well as pH. Recommended changes to improve DKA management are to expand teaching sessions to include Emergency Department (ED) doctors, as well as ED and medical nursing staff, to improve awareness of the correct management and diagnosis of DKA. Further emphasis will be placed on keeping a paper copy of the Trust Adult DKA management protocol in the patients’ notes.
Presentation: No date and time listed
OR03-6 Further Clinical Evaluation of Stem Cell-Derived Islet Replacement Therapy (VC-02) Demonstrates Production of C-Peptide with Improvements in Glycemic Control Parameters in Multiple Patients with Type 1 Diabetes and Hypoglycemia Unawareness
Authors: Bellin Melena , Daniels Mark , Foyt Howard , Keymeulen Bart , Kieffer Timothy , Kroon Evert , Pipeleers Daniel , Thompson David , Wang Richard , Jaiman Manasi 
Published: November 2022

Abstract
VC-02 combination product (PEC-Direct) is a clinical-stage regenerative medicine therapy being developed for patients with type 1 diabetes and hypoglycemia unawareness intended to restore homeostatic glycemic control. It is comprised of stem cell-derived pancreatic progenitors (PEC-01) loaded into a macroencapsulation device that facilitates the in-growth of blood vessels into the device lumen, supporting the maturation and differentiation of the graft into hormone-positive islet cells comprising glucose-responsive beta cells. Initial data from one patient (2021, Keymeulen) demonstrated clinically-relevant levels of stimulated C-peptide and corresponding improvements in glycemic control within six months after subcutaneous implantation. These improvements now include a time-in-range consistently &gt;90% and a persistent HbA1C &lt;7%.Enrollment of additional patients with negligible C-peptide levels in the ongoing VC02-101 study implanted with the same device configuration has now resulted in multiple patients demonstrating C-peptide levels ≥0.3 ng/mL. All patients are challenged with a mixed-meal tolerance test at baseline and post-implantation to detect and monitor increases in plasma C-peptide levels. In some cases, the increased C-peptide levels are observed to occur as soon as two months post-implant with subsequent increases resulting as the patients progress further into the treatment period as high as 0.4 ng/mL by five months with additional time points at longer periods of exposure pending. This progressive rise in beta cell function is consistent with preclinical findings showing time-dependent differentiation of the pancreatic progenitors into beta cells and subsequent increases in beta cell mass.The increases in plasma C-peptide levels also correlate with trends toward improved glycemic control parameters. Relative to baseline levels, improvements are observed in time-in-range data captured from continuous glucose monitoring, as well as substantial decreases in HbA1C by as much as 1.5%. These positive trends also correlate with decreases in the amount of exogenous insulin required by as much as 70%. Importantly, these data and observations have been obtained at separate clinical sites involving different surgeons, indicating that the achievement of functional engraftment of PEC-Direct is reproducible with proper product handling, surgical training, and patient compliance with an adjunctive immunosuppression regimen. These data provide further proof-of-concept that continued optimization of PEC-Direct can result in a functional cure for T1D.
Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.
PMON31 IL-4 Serum Levels Correlate with Triglycerides and VLDL in African American males
Authors: Johnson Abraham , Glover Jordan , Greene Natasha , Kimbro Sean 
Published: November 2022

Abstract

Background
Cytokines can play dual roles in diseases, while they signal the activation of the immune system, their mechanism of action results in inflammation. Low grade inflammation is often associated with metabolic diseases and a network of serum cytokines. IL-4 has been found to play a pro-inflammatory role in many conditions surrounding inflammation such as: atopic dermatitis and asthma. As it pertains to lipid metabolism IL4 has been shown to play a protective role in mice. A previous study has shown that IL4 regulates glucose and lipid metabolism by increasing sensitivity to insulin, inhibiting adipogenesis, and increasing glucose tolerance. Dysfunction in lipid metabolism can lead to other metabolic diseases such as cardiovascular disease, diabetes, and obesity. The molecular characterization of IL4's effect in metabolic diseases has yet to be completed. IL4 has been shown to correlate with serum triglyceride and cholesterol, VLDL levels. However, further studies must be carried out to illuminate the molecular cause of these relationships as well as other relationships among metabolic diseases.

Methods
A total of 68 serum samples were collected from 34 obese, normal HbA1c and 34 obese, elevated HbA1c African American men. Clinical metabolic parameters were determined using standard commercial kits administered by Laboratory Corporation of America. Thirty chemokines/cytokines were measured using a multiplexing assay Luminex X-MAP® technology. Descriptive statistics were computed for each variable for participants with normal and elevated HbA1c. Data are expressed as mean ± SEM. A series of unpaired t-test were computed to determine if there were significant differences between participants with and without elevated HbA1c. Pairwise Pearson Correlation (r) test was computed for each variable.

Results
In participants with normal HbA1c levels, IL-4 is positively correlated with VLDL (R= 0.6175, P=0.0014). There was no significant correlation in participants with elevated HbA1c in this study (R=0.08168, P=0.1758). Total cholesterol did not have any significant correlation with IL4 in this study; however, there was a positive correlation with IL-4 (R=0.6269, P=0.0013) and triglycerides in participants with normal HbA1c, no correlation seen in this study in participants with high HbA1c.

Conclusion
This data suggests that IL4-JAK-STAT pathway may play a role in the regulation of IL4, triglycerides, and VLDL in males. The correlations between IL-4 and both serum triglyceride and serum cholesterol, VLDL levels prompt the need to further study possible molecular relationships with other inflammatory biomarkers for metabolic diseases.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.