bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-649 Application of the New Cluster-Based Classification of Adult Onset Diabetes in a South Texas Veteran Population
Authors: Trejo Jonathan , Hernandez Lyan Gondin , Esteve Lucy M A , Vasquez Libia , Pinkson Sheila , Chen Xi , Koops Maureen , Tripathy Devjit 
Published: May 2020

Abstract
Recently a cluster-based classification of disease phenotypes has been developed as a tool to aid in improved characterization and management of diabetes. The majority of these studies have been completed in European populations, but it is unclear if these are applicable to other populations. Using these cohorts, we categorized patients in a South Texas VA diabetes clinic to evaluate if these phenotypes apply to that population. A retrospective cohort study was completed from August 2019 through October 2019, in which 120 patients’ records in the Audie Murphy VA Diabetes Clinic were reviewed for presence of macro and microvascular complications, type of anti-diabetic medication, lipid profile and HbA1c levels, and fasting C-peptide and GADab status. 86 patients who had anti-GADab and C-Peptide levels measured were then stratified into diabetic phenotype cohorts as defined by Ahlqvist et al. 2018, based on presence of diabetes associated autoantibodies, fasting C-peptide level, insulin use &gt;200 U/day, BMI, and age &gt;65. Six subjects belonged to the Severe Autoimmune Diabetes (SAID) cohort, with average GADab 713±301IU; 66% of the cohort had nephropathy, 33% had retinopathy. The Severe Insulin Deficiency (SIDD) cohort had 9 patients, with average fasting C-peptide of 0.58±0.08ng/ml, 44% of the cohort had retinopathy, nephropathy and CAD as complications. The Severe Insulin Resistant (SIRD) cohort had 26 patients; fasting C-peptide was 4.94±0.43ng/ml, 73% had nephropathy, 38% retinopathy and 46% CAD. The Mild Obesity Related (MOD) cohort had 35 patients with average BMI of 35±0.6 kg/m2 and average A1c 7.9±0.2%. Nephropathy was the most prevalent complication, present in 49% of the cohort. The Mild Age Related (MARD) cohort had 10 patients, with average age of 71±1.0 years, with nephropathy and CAD present in 66% of the cohort. The highest gross prevalence of nephropathy was in the SIRD cohort, whereas highest prevalence of retinopathy was in the SIDD cohort, both of which are concordant with the recently reported study, although not statistically significant (p=0.28 and 0.65, respectively). There was no difference in prevalence of CAD between the different categories of diabetes. These findings in a South Texas VA diabetes clinic population reflect agreement in diabetes associated complications in clusters of diabetes based on insulin resistance and insulin deficiency. Targeted intensification of therapy based on the major underlying pathophysiologic abnormalities may delay or prevent micro and macrovascular complications.
1. Ahlqvist E, et al. Novel Subgroups of Adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Endocrinology and Diabetes. 2018;6: 361-369.
SAT-662 Effects of SGLT Inhibitors or GLP1 Analogues on Glucose Homeostasis and Body Weight in Patients with Type 1 Diabetes: A Network Meta-Analysis
Authors: Lim Soo , Ji Kim Yoon 
Published: May 2020

Abstract
Objective: Despite intensive insulin treatment in patients with type 1 diabetes (T1D), many of them do not reach the glycemic target goal. We performed a network meta-analysis to evaluate the efficacy and safety of additional therapy to insulin in patients with T1D. Methods: We searched CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded from January 1970 until September 2019 to identify randomized controlled trials (RCTs) in T1D patients treated with insulin and metformin, sodium-glucose cotransporter (SGLT) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). We performed direct and indirect network meta-analysis using Bayesian models and generated rankings of the different hypoglycemia agents by generating mixed treatment comparison. Results: With 23 RCTs (n = 5,151), we performed the network meta-analysis using eight groups; 1) insulin alone, 2) insulin and metformin, 3) insulin and canagliflozin, 4) insulin and dapagliflozin, 5) insulin and empagliflozin, 6) insulin and sotagliflozin, 7) insulin and liraglutide, and 8) insulin and exenatide. Compared with insulin alone, HbA1c was significantly lower in the group treated with insulin and sotagliflozin (mean difference: -0.43%; 95% credible intervals: -0.62 to -0.23). Total daily insulin dose was significantly lower in the insulin and sotagliflozin group by 6.3 U/day than in insulin alone group. Compared with insulin alone, body weight was significantly decreased in the group treated with canagliflozin by 4.5kg, sotagliflozin by 2.8kg, and exenatide by 5.1 kg, respectively. Severe hypoglycemic episodes did not differ between the groups. Conclusions: In patients with T1D, sotagliflozin add-on to insulin decreased HbA1c levels, daily insulin dose, and body weight without hypoglycemia compared to insulin monotherapy. Combined treatment of canagliflozin or exenatide with insulin was effective in weight loss compared with insulin alone in these patients.
SAT-314 Pituitary and Neuroendocrine Tumors Exhibit Distinct Transcriptomes on Single Cell RNA Sequencing
Authors: Zhang Dongyun , Hugo Willy , Timothy Donahue , Mark Girgis , Bergsneider Marvin , Wang Marilene B , Heaney Anthony P 
Published: May 2020

Abstract
Neuroendocrine tumors (NETs) comprise a group of complex heterogeneous and increasingly prevalent neoplasms. They arise from diverse body regions, share derivation from primitive neuronal stem cells, secrete various bioactive peptides and exhibit a wide spectrum of tumor behavior from relatively indolent to rapidly progressive. Pituitary tumors represent 20% of intracranial tumors and share some features of NET histo-pathologic morphology, their excess hormone production and some have proposed re-naming pituitary tumors as PitNETs. However there has been no precise cell type composition comparison at the whole genome level in these two types of tumors. To explore intratumoral heterogeneity at a single cell resolution in pituitary and pancreatic NETs, we employed single cell RNA sequencing (scRNA-seq) to analyze in parallel cell populations from surgically resected pituitary tumors (n=4) and pancreatic NETs (pNET, n=2) using a 10x Genomics platform (v3). Using Cell Ranger pipeline for alignment and mapping, we obtained an average of 8,306±2,519 cells/sample with 1,516±822 genes/cell (mean reads/cell 67.9±30K). Seurat v3 was then used for read pre-filtering, normalization, and cluster identification. We identified 5 genes commonly expressed in both pNET and pituitary tumor populations, namely CALY (clathrin light chain binding GO:0032051), SPINT (peptidase inhibitor activity GO:0030414), CHGB (hormone activity GO:0005179), SCG5 (GTP binding GO:0005525) and SEZ6L2. As proof of their oral epidermal embryonic origin, the commonly expressed genes in 4 pituitary tumor samples include pituitary tissue restricted transcription factors (POU1F1, BEX1/2 GO:0033613), GNAS (G-protein beta/gamma-subunit complex binding GO:0031683), NLRP1 (peptidase activator activity involved in apoptotic process GO:0016505), PTN (protein phosphatase regulator activity GO:0019888) and ATP6V1G1 (ATPase binding GO:0051117). In parallel, 71 genes were present at high levels in pNET and involved in molecular functions such as calcium ion binding (HSPA5; ENPP2; C2CD4B; CALR; HSP90B1 GO:0005509) and endopeptidase inhibitor activity (PCSK1N; WFDC2 GO:0004866). Although our exploratory findings are limited to 6 samples, the robust commonly expressed genes within each tumor type clearly separated pituitary and pancreatic neuroendocrine tumors into distinct entities. We did observe conservation of chromogranins and prohormone convertases in these two tumor types, but it only represented a very small portion of overlap in transcriptome in pNETs. In summary, our findings suggest that pituitary and neuroendocrine tumors have only limited common molecular features, and by and large they stand as separate biologic populations. Our observations may begin to provide insight into the differences in tumor progression that are encountered clinically between pituitary tumors and pancreatic NETs.
MON-370 Treatment of Parathyroid Storm in a Patient with Traumatic Brain Injury: A Reversible Comatose State
Authors: Rhyu Jane , Wei Jeffrey , Darwin Christine Hema 
Published: May 2020

Abstract
Background:
Parathyroid storm, also known as parathyroid crisis, is a rare and under-recognized endocrine emergency due to severe hypercalcemia in patients with primary hyperparathyroidism. It is characterized by significantly elevated parathyroid hormone (PTH) levels even up to 20 times above the normal limit along with calcium levels &gt;15 mg/dl, leading to multiorgan dysfunction, notably altered mental status and acute kidney injury. Risk of mortality is high without urgent parathyroidectomy. We describe a case of a patient with acute traumatic brain injury and parathyroid storm with PTH &gt;1700 pg/ml (11-51) and Ca 15.4 mg/dl (8.6-10.4) in whom resection of a parathyroid adenoma reversed the comatose state.
Clinical Case:
Our patient is a 68 year-old male with no significant past medical history who sustained a fall off a 12-foot ladder complicated by right intracranial bleed s/p hemicraniectomy and multiple fractures, including left clavicle fracture with possible subclavian artery injury, left rib fractures, and right hip fracture s/p ORIF. The patient had a brief, partial improvement of mental status, followed by comatose state in the setting of rapidly rising calcium levels and acute kidney injury. In the setting of blood transfusions, the patient had an initial Ca of 8.8 mg/dl (8.6-10.4) on admission. The calcium levels rose over a week to 15.4 mg/dl with albumin of 2.4 g/dl (3.9-5.0), PTH levels from 953 pg/ml to &gt;1700 pg/ml (11-51) after tracheostomy, and creatinine from 0.69 mg/dl to peak of 2.0 mg/dl (0.60-1.30). In spite of IV hydration, calcitonin, cinacalcet up to 90mg twice daily, pamidronate 60mg IV, and several sessions of hemodialysis, the patient’s calcium did not normalize, and the patient remained comatose. Other labs showed phosphorus nadir of 1.4 mg/dl (2.3-4.4), 25-OH VitD 13 ng/ml (20-50), 1,25-OH VitD 9.8 pg/ml (19.9-79.3), VitA 0.6 mg/L (0.3-0.9), PTHrP &lt;2.0 pmol/L (0.0-2.3), normal SPEP/UPEP, and peak CK of 569 U/L (63-474). Sestamibi scan showed intense tracer uptake within a nodule near the suprasternal notch, and parathyroid 4D-CT showed a left 17mm pretracheal lesion with cystic degeneration along the superior margin of the manubrium. The patient subsequently underwent parathyroidectomy of an ectopic cystic mass with normalization of calcium and PTH levels. Pathology revealed a 0.8 gram, 1.5 x 1.0 x 0.3 cm enlarged, hypercellular parathyroid. The patient woke up from his comatose state immediately after surgery with progressive improvement in mental status back to baseline, other than left-sided weakness.
Conclusion:
Our case highlights the importance of surgical management as an effective cure for parathyroid crisis and underscores the associated critical and significant rise in calcium and PTH levels, which was resistant to medical treatment.
SUN-025 Obesity Severity and Polycystic Ovary Syndrome in an Ethnically Diverse Cohort of Adolescent Girls
Authors: Khil Jaclyn , Chandra Malini , Ramalingam Nirmala D , Greenspan Louise C , Lo Joan Chia-Mei 
Published: May 2020

Abstract
INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting young women and may present as early as adolescence. Early recognition is important, as polycystic ovary syndrome (PCOS) is associated with increased cardiometabolic risk and type 2 diabetes mellitus. The risk of PCOS increases with obesity, but fewer studies have explored the burden of PCOS in children with obesity within healthcare settings. In this study, we examined the proportion of adolescent girls with obesity who also had diagnosed PCOS and the relationship between PCOS and obesity severity.
METHODS: From an existing cohort of nearly 8000 children age 3-17 with obesity (Body Mass Index, BMI ≥95th percentile) who were seen at pediatric well-child visits and identified for weight management based on BMI, we classified the subgroup of girls age 12-17 years who had moderate (BMI 100-119% of the 95th percentile) and severe (BMI ≥120% of the 95th percentile) obesity by PCOS status. Diagnosed PCOS was identified based on a visit diagnosis code for PCOS (ICD-9 256.4) within one year of the well child visit.
RESULTS: We identified 1478 adolescent girls (age 12-17) with obesity, among whom 76 (5%) had a PCOS diagnosis. The burden of PCOS varied by race, including 4% among white, 7% among black, 5% among Hispanic, and 8% among Asians, respectively. The proportion with diagnosed PCOS was greater in severely obese patients (9%) compared to moderately obese (3%). By race/ethnicity, the proportion with PCOS among moderately obese/severely obese girls were as follows: white 2%/8%, black 4%/10%, and Hispanic 2%/9%, respectively. The Asian population had a higher proportion of PCOS (10%) among girls with moderate obesity, as fewer Asian girls had severe obesity overall.
CONCLUSION: Among adolescent girls with obesity, the burden of PCOS varied by race/ethnicity and level of obesity. Increasing severity of obesity was associated with a greater proportion of girls having diagnosed PCOS, a trend that was reflected in white, black and Hispanic adolescent girls but not Asians, the latter due to their lower range BMI. These data highlight the prevalence of PCOS among adolescent girls with obesity and support the need for early identification and management prior to adulthood.
SAT-613 Comparison of CV Risk Scores to Evaluate Cardiovascular Risks in Thai Type 2 Diabetes
Authors: Waisayanand Nipawan , Phrommintikul Arintaya , Mangklabruks Ampica 
Published: May 2020

Abstract
Objective: Various cardiovascular risk scores have been developed and the RAMA-EGAT risk score was developed by Thai database with minority of diabetes. This study aims to compare the predictability of the ADVANCE, UKPDS, SCORE, Framingham Risk Score (FRS) and RAMA-EGAT risk score for carotid atherosclerosis, arterial stiffness and peripheral arterial disease in Thai T2DM patients. Methods: A cross-sectional study was conducted in T2DM patients without established CVD at a tertiary care hospital. Demographic and DM-specific data were collected. Carotid intima-media thickness (CIMT), carotid plaque, cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were measured as the markers of atherosclerosis. Risks of CVD were calculated according to the ADVANCE, UKPDS, SCORE, FRS and RAMA-EGAT risk scores. These risk scores were correlated with the atherosclerotic markers by odds ratio using logistic regression and the proper points of the risk scores to predict atherosclerosis were calculated by the areas under the curve (AUC). Results: There were 180 T2DM participants with the mean age of 60-year-old, diabetes duration of 13 years and mean A1C 7.4%. The highest sensitive risk score was FRS, following by UKPDS, SCORE, ADVANCE and RAMA-EGAT risk score, which indicated high-risk patients as 44.8%, 27.6%, 18.9%, 13.8% and 0% accordingly. There were 40.3% of the patients with arterial stiffness detected by CAVI &gt; 9, 24.0% with carotid atherosclerosis defined by CIMT &gt; 0.07 mm or presenting of carotid plague and 8.3% with ABI &lt; 0.9. The odds ratios (OR) of 4 risk scores increased by the quartiles for carotid plaque, CIMT, CAVI and ABI while the OR of RAMA-EGAT scores increased by the quartiles only for carotid plaque. The highest quartile of ADVANCE, UKPDS, SCORE and FRS significantly (P&lt;0.01) increased the risk of abnormal CIMT; OR 2.64-8.75, carotid plaque; OR 1.51-11.21, CAVI; OR 11.38-19.00, and ABI; OR 1.18-12.57. The highest quartile of RAMA-EGAT score significantly increased the risk of carotid plaque; OR 5.35 (1.44-19.91) P&lt;0.01. ROC analysis revealed that ADVANCE &gt; 3.0% in 4-year, UKPDS &gt; 11% in 10-year, fatal-SCORE &gt; 6% in 10-year and FRS &gt; 18% in 10-year were predictive of carotid atherosclerosis with sensitivity of 76-84% and specificity of 61-69% and they were predictive of arterial stiffness with the sensitivity of 71-80% and specificity of 64-68%. Conclusion: There was no significant difference when comparing the predictability of the ADVANCE, UKPDS, FRS and SCORE risk estimation for carotid atherosclerosis, arterial stiffness and peripheral arterial disease and they were more correlative with atherosclerotic markers than RAMA-EGAT score in Thai type 2 diabetic patients.
SAT-712 Computational Study of the Effect of Androgen Receptor BF 3 Site Mutations on DDE Binding
Authors: Chowdhury Muniruzzaman , Dean Frank , Kotsikorou Evangelia 
Published: May 2020

Abstract
Exposure to endocrine disrupting chemicals (EDCs) affects the function of the androgen receptor (AR) causing reproductive system problems such as reduced sperm counts, increased infertility, testicular dysgenesis syndrome, and testicular and prostate cancers, as well as reduced bone mass and diabetes mellitus in males. Experimental results have shown that the presence of EDCs such as the diphenyl compound DDT and its analogue DDE, allosterically cause the release of the stably bound dihydrotestosterone (DHT) from the steroid binding site of the AR ligand binding domain. It was hypothesized that EDCs mediate this effect via binding to the Binding Function 3 (BF 3) surface binding site. Five mutations of three BF 3 amino acids (F673K, F673W, G724R, G724M, and L830D) showed that the ability of DDE to inhibit AR activity was reduced, suggesting that DDE binds to the BF 3 site and allosterically regulates AR activity. In this study, the Induced Fit Docking protocol of the Schrodinger software was used to dock DDE into the BF 3 site of the wild type AR ligand binding domain as well as the five mutant BF 3 sites. The docking poses generated for each receptor were clustered and representative structures were selected. The receptor-ligand complexes were energy minimized using the Schrodinger module Macromodel. Finally, the energy of interaction between DDE and the BF 3 site amino acids was evaluated for each of the selected docks of the wild type and mutant receptors. The relationship between the energies of interaction and the experimental results for DDE inhibition of the mutant AR activities will be discussed.
SAT-621 Framingham Cardiovascular Disease 10-Year-Risk Score Is Associated with Myocardial Perfusion in Asymptomatic Diabetic Patients
Authors: Deng Mingyan 
Published: May 2020

Abstract
Background: Even without atherosclerosis, diabetes increases the risk of death from coronary heart disease and heart failure. Myocardial perfusion dysfunction may occur in the early stage of diabetic cardiomyopathy, but its examination method is relatively complex. It is very important to carry out targeted cardiac screening to find the factors related to diabetic myocardial perfusion in the early stage.
Methods: We enrolled 77 patients with diabetes and 30 controls, performed anthropometric and laboratory tests such as blood glucose and lipids, and calculated Framingham Cardiovascular Disease 10-year-risk Score (FRS). All participants underwent cardiac magnetic resonance examinations and recorded their cardiac structure, functional indicators (such as ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume(SV), peak filling rate (PFR),myocardial perfusion index (maximum upslope (Slope), half time to maximum signal intensity (Time50Max (s)), time to maximum signal intensity (TimeMax (s)), the maximum signal intensity (MaxSI),, basic signal intensity (Baseline),the ratio of MaxSI and Baseline ((MaxSI (BL) %), the difference value between MaxSI and Baseline (MaxSI (BL))).
Results: Compared with normal group, no cardiovascular symptoms of left ventricular and right ventricular systolic function in patients with diabetes and end-diastolic and end systolic volume had no obvious difference, left ventricular PFR is lower than normal (279.65 + 57.62 vs. 322.57 + / - 78.29, p = 0.02), in the subgroup analysis we found that the FRS high-risk groups, ventricular septal thickening tend to, and Slope, MaxSI, MaxSI BL (%), MaxSI (BL) were significantly lower than the high risk group, Time50Max and TimeMax were significantly longer than the non-high-risk group, and FRS was negatively correlated with Slope, MaxSI(%BL) and positively correlated with TimeMax(s) and Time50Max(s), with statistical significance.
Conclusion: Systolic function remains and diastolic function decreases in asymptomatic diabetic patients. Moreover, the patients with high risk of FRS had significant decreased perfusion function, and the quantitative indexes of perfusion function were closely related to FRS. It is of great value to pay attention to the changes of FRS score for early screening and diagnosis of diabetic heart disease.
SUN-657 The Effect of Simvastatin on Glucose Metabolism in Primary Human Muscle Cells
Authors: Mäkinen Selina , Datta-Sengupta Neeta , Nguyen Yen , Kyrylenko Petro , Laakso Markku , Koistinen Heikki A 
Published: May 2020

Abstract
Statin use, especially treatment with simvastatin, is associated with impaired insulin secretion and whole-body insulin sensitivity, and increased risk for T2D. Here, we investigated the direct effects of lactone- and acid-forms of simvastatin on glucose metabolism in primary human skeletal muscle cells. Exposure of human myotubes to lactone-form simvastatin for 48 h increased glucose uptake and glucose incorporation into glycogen, whereas the acid-form did not affect glucose uptake and decreased glucose incorporation into glycogen. These metabolic actions were accompanied by changes in insulin signaling, as phosphorylation of AS160 and GSK3β was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both lactone and acid-forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. Collectively these data indicate that lactone- and acid forms of simvastatin exhibit differences such that lactone-form increases, and acid-form impairs glucose incorporation into glycogen. Exposure to either form of simvastatin, however, impairs glycolysis and mitochondrial oxidative metabolism in human skeletal muscle cells.