bluuebunny/crossref_metadata_2025_split huggingface dataset:
7834 Case Series using intravenous insulin to treat Severe Hypertriglyceridemia
Authors: Khan Farooq , Eltayeb Musab , Ryan James , Murphy Matthew 
Published: October 2024

Abstract
Disclosure: F. Khan: None. M. Eltayeb: None. J. Ryan: None. M. Murphy: None.
Background: Very severe hypertriglyceridemia (&gt;22.4 mmol/L) is associated with high risk of acute pancreatitis and atherosclerotic cardiac events. Conventional treatments tend not to yield immediate results. There is a lack of clinical guidelines for acute very severe HTG; and potential therapeutic options such as insulin, heparin, plasmapheresis, and octreotide have been tested and shown to be effective. We present a series of four cases where intravenous insulin was useful as an emergency treatment for severe HTG. Clinical Cases: Case 1: 48-year-old male was admitted with very severe hypertriglyceridemia with triglycerides levels of 45.3mmol/L (reference range: 0-1.7 mmol/L), new diagnosis Diabetes Mellitus with ketosis and was started on intravenous insulin. After three days of intravenous insulin, triglyceride levels reduced by 47.93%. Case 2: 28-year-old male, admitted with acute pancreatitis secondary to very severe hypertriglyceridemia (66.9mmol/L), a new diagnosis of Diabetes Mellitus with ketosis, was commenced on intravenous insulin. There was a reduction in triglycerides by 77.5% in 3 days and 96.6% in 9 days with intravenous insulin treatment. Case 3: 29-year-old female, admitted with new diagnosis Diabetes Mellitus with ketosis and very severe hypertriglyceridemia (50.67mmol/L) was treated with intravenous insulin. Total triglyceride reduction was 65.8% in 48 hours. Case 4: 27-year-old female, admitted Diabetic Ketoacidosis (DKA), new diagnosis Diabetes Mellitus, very severe hypertriglyceridemia (24.3mmol/L) was treated with intravenous insulin. 65.8% reduction in triglycerides was seen in after 72 hours. Conclusion: These cases show the efficacy of insulin infusion with encouraging results, especially when plasmapheresis is not readily available however larger studies including a randomized controlled trials is needed to confirm the efficacy and safety for the use of intravenous insulin to establish a universal and effective treatment for this severe life-threatening metabolic disorder. Reference: Simha V. Management of hypertriglyceridemia BMJ 2020; 371 :m3109 doi:10.1136/bmj.m3109
Presentation: 6/3/2024
5156 Circulating MicroRNA-based Biomarker Combinations for Differentiating Uni- and Bilateral Primary Aldosteronism Using a Machine Learning Approach
Authors: Vekony Balint , Nyiro Gabor , Herold Zoltan , Fekete Janos , Ceccato Filippo , Gruber Sven , Kurzinger Lydia , Parasiliti-Caprino Mirko , Szeredas Balint , Nazri Siti K S M , Fell Vanessa , Bassiony Mohamed , Azizan Elena A , Bancos Irina , Beuschlein Felix , Igaz Peter 
Published: October 2024

Abstract
Disclosure: B. Vekony: None. G. Nyiro: None. Z. Herold: None. J. Fekete: None. F. Ceccato: None. S. Gruber: None. L. Kurzinger: None. M. Parasiliti-Caprino: None. B. Szeredas: None. S.K. Nazri: None. V. Fell: None. M. Bassiony: None. E.A. Azizan: None. I. Bancos: None. F. Beuschlein: None. P. Igaz: None.
Background: The differentiation of uni- and bilateral forms of primary aldosteronism (PA) is of pivotal clinical relevance. Whereas unilateral PA warrants surgical treatment, bilateral PA is treated by aldosterone antagonists. The most reliable way to differentiate these two entities is adrenal venous sampling (AVS) that is an invasive method with limited availability and requiring great expertise. Aim: To develop a circulating blood-borne microRNA-based approach using machine learning for the differentiation of uni- and bilateral PA. Methods: Circulating microRNA profiling on an Illumina MiSeq platform was performed on total RNA samples isolated from EDTA-anticoagulated blood specimens taken by AVS from 18 pairs of right and left suprarenal veins (10 uni-, 8 bilateral PA). Significantly differentially expressed microRNAs were analyzed by a neural network (90-10% learner-tester cross-validation simulation). From the top 29 significantly differentially expressed microRNAs, 9 were selected for validation by Taqman RT-qPCR on a separate cohort of 30 AVS-confirmed samples (15-15 uni- and bilateral forms) both on plasma samples from adrenal as well as from peripheral veins. The method was finally tested on another independent cohort of peripheral blood samples from 80 patients (40 uni- and 40 bilateral PA). Results: Regarding the 9 microRNAs selected for validation, microRNA abundance was non-significantly lower in peripheral samples compared to AVS samples. By analyzing peripheral plasma samples, ten combinations of 4-8 microRNAs from the pool of 9 microRNAs turned out to have maximal sensitivity and specificity values over 85 %. The best combination included 6 microRNAs with a sensitivity of 86.3 % and a specificity of 87.91 % (AUC = 0.871). The inclusion of further parameters such as imaging, potassium and renin levels did not improve the model’s performance. Conclusion: The analysis of circulating blood-borne microRNAs represents a minimally invasive and potentially reliable way of differentiating uni- and bilateral PA. If bilateral PA is confirmed by the model, no more localization efforts would be necessary thus simplifying the management of PA patients. This would be relevant both from the patient’s and a public health perspective.
Presentation: 6/3/2024
7386 GlycA as a Novel Biomarker of Systemic Inflammation: Determinants and Implications in South Asians
Authors: Deven A , Ramanathan A , Bukhari K , Rabel A , Muniyappa R 
Published: October 2024

Abstract
Disclosure: A. Deven: None. A. Ramanathan: None. K. Bukhari: None. A. Rabel: None. R. Muniyappa: None.
Background: South Asians are at an increased risk for developing diabetes and cardiovascular disease compared with their European counterparts. Increased systemic inflammation is a key contributor to cardiometabolic dysfunction. GlycA, a novel inflammatory biomarker, predicts incident type 2 diabetes mellitus (T2DM) in population-based studies of South Asians. However, the determinants of GlycA in this population are unknown. Objective: To investigate the relationships between GlycA, body composition, glycemia, lipoproteins, insulin sensitivity, and beta cell function in healthy individuals. Methods: This cross-sectional study involved 59 adults without T2DM (body mass index: 26.5 ± 5.2 kg/m2, age 36.5 ± 8.3 years, 44 % female) who underwent a frequently sampled intravenous glucose tolerance test and a mixed meal in the fasted state. Body composition was determined by dual-energy X-ray absorptiometry. Insulin sensitivity and beta cell function parameters were calculated by minimal model analysis. Nuclear magnetic resonance was used to measure GlycA and lipoprotein profiles. Results: GlycA was found to be positively associated with BMI, total fat mass, relative fat mass, total cholesterol, free fatty acids, LDL cholesterol, small LDL-particle number, triglycerides, triglyceride-rich lipoproteins particles (TRLP), fasting insulin, and insulin secretion. GlycA was also negatively associated with measures of insulin sensitivity, HDL, and large-HDL-particle number. The forward stepwise regression model, explaining 54% of the variance in GlycA levels (R2=0.54, P &lt;.0001), identified relative fat mass, insulin sensitivity derived from mixed meal, and large HDL particle number as independent predictors. Conclusions: GlycA exhibited an independent association with relative fat mass, insulin resistance, and reduced levels of HDL particles (HDL-P) in South Asians, suggesting its potential as a predictive biomarker in this demographic. Future research should focus on exploring the underlying mechanisms driving these associations.
Presentation: 6/3/2024
8575 Hepatic Steatosis Index as a non-invasive marker for liver steatosis in patients with endogenous Cushing Syndrome, ERCUSYN Krakow database
Authors: Minasyan M , Gamrat A , Hubalewska-Dydejczyk A , Valassi E , Gilis-Januszewska A 
Published: October 2024

Abstract
Disclosure: M. Minasyan: None. A. Gamrat: None. A. Hubalewska-Dydejczyk: None. E. Valassi: None. A. Gilis-Januszewska: None.
Introduction: Liver Steatosis(LS) can be one of the metabolic complications of Cushing Syndrome(CS). The data on the impact of cortisol on liver function are very limited, and there is only one study reporting a prevalence of LS of roughly 20%. Hepatic Steatosis Index (HSI) predicts LS based on ALT, AST, BMI, sex and co-existence of diabetes mellitus/impaired glucose intolerance. Objectives: To evaluate the prevalence of LS in patients with CS at the time of diagnosis by using HSI. Methods: We analyzed retrospectively adult patients from the ERCUSYN, Krakow database with complete HSI data available. 82 of 135 patients, aged 27-87 years, predominantly women (N=64), were eligible for the study. The HSI score was calculated using the following formula: 8×(ALT:AST)+BMI+2(if type 2 diabetes)+2(if female). Collected data were from the baseline CS diagnosis. Patients with score 36 or above were classified as having a high probability of LS. We compared HSI results with the liver steatosis diagnosed based on abdominal ultrasonography (USG) findings and clinical and demographic factors. Results: High HSI was observed in 81.7% patients (82.8% of females, 77.8% of males). HSI was elevated in 85%, 80% and 73% of patients with pituitary, adrenal and ectopic CS respectively. 41% of patients with elevated HSI were obese. HSI was elevated in among: 100% patients with confirmed liver steatosis on USG, 72% patients with normal USG and 78% patients who did not undergo USG. Conclusions: The prevalence of liver steatosis in active CS may be higher than previously reported. Further investigation should be undertaken to show if patients with high risk of LS based on HSI and normal liver image on USG, may benefit from liver MRI in order to confirm the diagnosis.
Presentation: 6/3/2024
5185 A Meta-Analysis Evaluating the Efficacy of Liraglutide in Reducing Cardiovascular Complications Among Patients With Type 2 Diabetes
Authors: Del Rosario Michelle Panol , Ong-Ramos Celeste 
Published: October 2024

Abstract
Disclosure: M.P. Del Rosario: None. C. Ong-Ramos: None.
Background: The objective of this study was to determine the efficacy of Liraglutide in reducing cardiovascular complications Methodology: Literature searches of electronic databases (PubMed and ScienceDirect) were performed to identify relevant studies. Relevant journals included were electronically searched for randomized controlled trials (RCTs) regarding the use of Liraglutide versus placebo in reducing the rate of cardiovascular complications. Data extraction and quality assessment were done from independent reviewers. Statistical analysis of the study was accomplished using Cochrane Systematic Review Software Review Manager. A p-value of less than 0.05 for the observed effect size was considered statistically significant. Results: A total of 2 RCTs with 16, 977 patients were included in this meta-analysis. The results showed that in the Liraglutide group there is a lower rate of the following: Major Adverse Cardiovascular Events (MACE) (risk ratio of 0.86 [0.78, 0.95]), cardiovascular events (risk ratio 0.75 [0.63, 0.89]), and all-cause mortality (risk ratio 0.81 [0.70, 0.93]), but is not statistically significant when compared to the placebo group in terms of non-fatal myocardial infarction and and non-fatal stroke. There is no significant difference in rates of severe adverse events in general (p &gt; 0.05). However, Liraglutide caused significant reduction in rates of severe hypoglycemia as an independent secondary outcome (p &lt; 0.05). Conclusions: Compared with placebo, Liraglutide provided significant reduction in MACE, cardiovascular events, all-cause mortality and severe hypoglycemia as an adverse event.
Presentation: 6/3/2024
12503 An Observational Study Of The Glycemic Variability In Type 1 Diabetes Mellitus Women Preconception And During Pregnancy And Its Associations With Adverse Maternal And Neonatal Outcomes
Authors: Avula Sreekant , Ankireddypalli Anvitha Reddy , Tessier Katelyn , Seaquist Elizabeth Rachel 
Published: October 2024

Abstract
Disclosure: S. Avula: None. A.R. Ankireddypalli: None. K. Tessier: None. E.R. Seaquist: None.
Background: Pregnancy in T1 diabetes mellitus (T1DM) women is associated with increased risk of maternal/fetal complications. Despite glycemic optimization during pregnancy in T1DM, offspring are at increased risk for neonatal complications. Aim: To examine glycemic variability by continuous glucose monitor (CGM) preconception and during pregnancy by trimester and assess the association with adverse maternal/fetal outcomes. Methods: This was a retrospective cohort study of pregnant patients with T1DM who used real-time CGM and delivered at a U.S. tertiary center (2012-2023). Multiple gestations, Cystic fibrosis-related diabetes (CFRD), twin or multiple births, and no valid CGM data for at least one trimester were excluded. 63 met the inclusion criteria. The primary outcome was composite neonatal morbidity (CNM), including large or small for gestational age (LGA/SGA), NICU admission, neonatal hypoglycemia, shoulder dystocia, respiratory distress syndrome, APGAR 1 or 5 minutes &lt; 7, prematurity (&lt;37 weeks), intrauterine growth restriction (IUGR), CPAP, and ventilator. We also collected data about maternal outcomes. Results:54 patients (86%) met at least one outcome included in the CNM. 20 patients (32%) were LGA, 3 (5%) were SGA, 32 (51%) premature, 29 (46%) required NICU admission, 44 (70%) had neonatal hypoglycemia, 3 (5%) had shoulder dystocia, 23 (37%) had respiratory distress, 22 (35%) needed CPAP, 3 (5%) were on ventilator, 11 (18%) had APGAR 1 minute &lt;7. Among maternal outcomes, 18 (29%) developed pre-eclampsia, and 46 (73%) had a cesarean delivery. Overall, individuals with neonatal morbidity had a lower target in range (TIR) and higher target above range(TAR), average glucose, standard deviation(SD), and coefficient of variation (CV) compared with those without the primary composite, but statistical significance was seen for average glucose and TAR. For every 5 mg/dl increase in average glucose (mean of the 3-trimester values), there was a 25% increase in odds of neonatal morbidity (OR 1.25; 95% CI 1.04-1.56; p=0.028). There was a significant association between 1st trimester SD and neonatal morbidity (OR 1.11; 95% CI 1.02-1.24; p=0.027). There was a trend toward significance between the 3rd-trimester average blood glucose and neonatal morbidity (OR 1.26; 95% CI 1.02-1.63; p=0.051). Conclusion: In our single-center cohort, we found maternal average glucose and TAR, as well as first trimester SD, were significantly associated with CNM. This confirms that maternal hyperglycemia and demonstrates that first trimester SD are associated with poorer neonatal outcomes.
Presentation: 6/1/2024
9207 Anoctamin 4 in the Area Postrema Regulates Glucose and Energy Homeostasis
Authors: Tu Longlong , Xu Yong 
Published: October 2024

Abstract
Disclosure: L. Tu: None. Y. Xu: None.
Located on the floor of the 4th ventricle within the dorsal surface of the medulla oblongata, the area postrema (AP) is a circumventricular organ where a proper blood-brain barrier is missing. Numerous studies reveal that neurons in the AP are implicated into suppression of food intake (e.g., glucagon-like peptide 1 (GLP-1)-mediated anorexia), but the role of AP neurons in whole-body glucose homeostasis is less investigated. Here we identified and fully characterized the physiological functions of anoctamin-4 (Ano4, a calcium activated chloride channel)1 in the AP. CRISPR-mediated deletion of Ano4 in the AP caused a lower body weight and reduced blood glucose, concurrent with an improved glucose tolerance and increased insulin sensitivity. Chemogenetic activation of Ano4-expressing neurons in the AP (APAno4) increased food intake and blood glucose, and did not induce conditioned flavor avoidance. Both Ano4 neurons and non-Ano4 neurons (i.e., neurons do not express Ano4) sent projections to the lateral parabrachial nucleus (LPBN). Optogenetic stimulation of APAno4 ◊ LPBN circuit promoted feeding behavior and increased blood glucose, whereas stimulation of APnon-Ano4 ◊ LPBN circuit inhibited food intake and did not influence glucose homeostasis. Finally, RNAscope studies reveal that 45.7% of APAno4 neurons are glutamatergic neurons, and 41.8% of them are GABAergic neurons. Furthermore, APAno4 neurons showed only a 2.6% overlap with Glp-1r-expressing neurons in the AP, but had a 60.8% co-localization with protein tyrosine phosphatase receptor δ2, which serves as orexigenic asprosin receptor. Together, our results indicate that Ano4 neurons in the AP are the first reported orexigenic neurons, and represent potential therapeutic targets for human diseases with glucose imbalance and abnormal feeding behavior. Reference: (1) Tu, L. et al. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. J Clin Invest 133,14. (2023). (2) Mishra, I. et al. Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor. Cell Metab 34, 549-563. (2022).
Presentation: 6/2/2024
9300 Anti-PD1 induces T1D in an HLA-DQ8, HLA-A2.1 mouse model
Authors: Houeiss Pamela , luce Sandrine , Le-Gall Morgane , Onifarasoaniaina Rachel , Boitard Christian 
Published: October 2024

Abstract
Disclosure: P. Houeiss: None. S. luce: None. C. Boitard: None.
Anti-PD1 is an immune checkpoint inhibitor that has revolutionized cancer treatment. It blocks the interaction between PD1, a receptor on the surface of activated or exhausted T cells, and its ligands PDL1 and PDL2, to inhibit the immune response. However, anti-PD1 induces T1D in 0.4-2% of patients raising questions about the risk factors and the mechanisms behind T1D development. Since the pancreas of these patients is inaccessible, we focus on autoimmune diabetes induction in a transgenic mouse model modified to express the T1D susceptibility genes HLA-DQ8, HLA-A2.1 and the human preproinsulin and on identifying new targets to prevent or treat this disease. Thus, 8 to 12 weeks old mice were treated initially with 500 micrograms of anti-PD1 followed by 250 micrograms every other day for 10 days. Control mice received 6 injections of PBS. Mice were followed up for evidence of hyperglycemia for 60 days. Cells and tissues from the pancreas, and the spleens were isolated 15-, 30- or 60-days post-treatment initiation and analyzed by flow cytometry and immunohistochemistry. Although diabetes incidence in treated mice was 14% (n=14), insulitis incidence progressively increased over time reaching 86% on D60 (p=0.005). On Day 15, in the spleen, a significant 10% increase of CD4+Foxp3+CD25- T cells at the expense of the CD4+Foxp3- T cells were seen in the treatment group as compared to the control (37.1±4.25 vs 26±3.5, p&lt;0.01, n=5 per group). In the treatment group, PD1 expression significantly increased on CD4+Foxp3+ T cells whereas PDL1 expression increased on CD4+Foxp3- and CD8+ T cells (p&lt;0.01). On D30, in the pancreas, infiltrates show positive staining for F4/80+, CD4+ and CD8+ T cells with scarce foxp3+ T cells. While the absolute percentage of CD4+Foxp3+ T cells increased in the insulitis and diabetes group, their percentage among CD3+ T cells decreased in the insulitis (10.2%) and diabetes group (3.9%) as compared to the control group (13.5%). Infiltrates were concentrated around the islets and the efferent and afferent vessels, and extended to the exocrine pancreas, leading to secondary acinar destruction. In the pancreatic infiltrates from anti-PD1 treated mice, we noted a significant increase in CD4+ T cells recognizing Ins13-21 monomers as compared to the negative control. PD1 blockade induced an insulitis characterized by a Treg to effector T cells imbalance. Thus, it acted on the early phase of T1D. In conclusion, this model describes a new T1D endotype that shares similarities with ICI induced diabetes in patients.
Presentation: 6/2/2024
6560 Atypical Diabetes Mellitus in a Mother-Son Pair with Multiple Autoimmune Conditions & Pathogenic Variant in BCL11B Inherited from the Mother
Authors: Elrajabi Rawan , Gurtunca Nursen 
Published: October 2024

Abstract
Disclosure: R. Elrajabi: None. N. Gurtunca: None.
The etiology of diabetes can be challenging to determine at times and misdiagnosis is common in all age groups. To provide the right treatment and enhance glycemic control, which results in better outcomes and fewer comorbidities, an accurate diagnosis is crucial. We describe a mother-son pair who share a pathogenic variant in BCL11B gene with multiple autoimmune conditions including atypical autoimmune DM. A 13 year old young boy with a history of 33-week prematurity, developmental delay, autoimmune hypothyroidism, and vitiligo presented with concerns for DM given mother’s recent diagnosis of DM treated with Metformin and GLP-1 receptor agonist with poor control of her DM. His mother has a learning disability, hypothyroidism, alopecia totalis, vitiligo and hypertension. Interestingly, he and his mother share a genetic variant in BCL11B gene detected on whole exome sequencing sent as part of the workup of developmental delay. His weight and height were in the 13.5% and 13.9% centiles, respectively. He has vitiligo, but other than that, the physical examination was unremarkable. He is prepubertal. HbA1c was high, 6.4% despite the presence of anemia. An oral glucose tolerance test (OGTT) was consistent with DM as was his repeat HbA1c of 7.1%. He had elevated IA 2, zinc transporter 8, and GAD 65 antibodies, all consistent with autoimmune DM. He was admitted to the hospital and started on both long-acting and short acting insulin via multiple daily injections. BCL11B is a transcription factor that is expressed in all T cells and regulates important processes involved in T cell growth, survival, and function, including Treg cells and Foxp3 activity. Autoimmune diseases have been linked to abnormal Treg activity and Foxp3 deficiency. BCL11B functions as a checkpoint required for T cell lineage commitment while minimizing natural killer cell potential. Impaired BCL11B activity at a young age result in severe whole-body autoimmunity, defined by a fully stimulated immune system similar to animals lacking functioning Treg cells. DM associated with BCL11B variant has not previously been reported. If we follow the theory that autoimmunity affects beta cell function or mass, this patient's and his mother's DM and autoimmune disorders are most likely connected to the BCL11B variation they share.
Presentation: 6/2/2024