bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB126 Real-World Safety and Effectiveness of Insulin Glargine 300 U/ML (Gla-300) in People With Type 2 Diabetes Who Fast During Ramadan
Authors: Hassanein Mohamed , Buyukbese Mehmet Akif , Malek Rachid , Pilorget Valérie , Naqvi Mubarak , Berthou Baptiste , Shaltout Inass , Sahay Rakesh Kumar 
Published: May 2020

Abstract
ORION was a prospective, observational study evaluating the safety and effectiveness of the second-generation basal insulin analog Gla-300 in people with type 2 diabetes (T2DM) who fast during Ramadan. Adults with T2DM who intended to fast for ≥15 days during Ramadan, had taken Gla-300 for ≥8 weeks prior to inclusion, and intended to continue its use during Ramadan were enrolled in 11 countries. During Ramadan, Gla-300 treatment was adjusted as per routine practice by the treating physician. Overall, the majority of people (402 [85%]) fasted for the entire Ramadan period and 10.8% fasted for ≥25 days but with at least one missed day. Mean (SD) age was 54.4 (11.0) years, 51.7% were male, BMI was 29.7 (5.3) kg/m2, and duration of diabetes was 10.7 (7.0) years. Risks of diabetes-related complications associated with fasting were assessed by physicians according to IDF-DAR fasting risk category; risk was low/moderate in 82.8%, high in 14.3%, and very high in 2.9% of people. The proportion of people with ≥1 severe and/or documented symptomatic (SMPG ≤70 mg/dL) hypoglycemia event was low (2.2% [event rate: 0.021 per participant-month (PPM)] in pre-Ramadan, 2.6% [0.039 PPM] in Ramadan and 0.2% in post-Ramadan [0.003 PPM]). Overall, 0.8% (0.005 PPM) of participants experienced severe and/or documented symptomatic hypoglycemia at SMPG &lt;54 mg/dL, and only during pre-Ramadan. No participants had severe hypoglycemia during Ramadan or post-Ramadan; 1 participant had severe hypoglycemia pre-Ramadan. Most of those who experienced symptomatic hypoglycemia during Ramadan did so during fasting hours (11/13 people). Reductions were shown pre- to post-Ramadan for mean (SD) HbA1c (8.10 % [1.29] pre-Ramadan to 7.64 % [1.05] post-Ramadan; change of −0.44 % [0.97]), FPG (144.3 [45.8] mg/dL pre-Ramadan to 128.5 [37.8] mg/dL post-Ramadan; change of −13.5 [44.1] mg/dL), and fasting SMPG (130.7 [32.9] mg/dL pre-Ramadan to 126.8 [28.5] mg/dL post-Ramadan; change of −3.3 [26.6] mg/dL). Mean Gla-300 dose was reduced slightly between pre-Ramadan and Ramadan (25.6 [11.9] U/0.32 [0.14] U/kg pre-Ramadan to 24.4 [11.5] U/0.30 [0.13] U/kg in Ramadan) and returned to 26.0 (12.2) U/0.32 (0.14) U/kg in the post-Ramadan period. AE incidence was low (5.5%); 3 (0.6%) participants had an AE of hyperglycemia, 2 (0.4%) during Ramadan. In this study, performed in a real-world setting, incidence of hypoglycemia was low in people with T2DM treated with Gla-300 who fasted for Ramadan, with no incidence of severe hypoglycemia during the Ramadan period; HbA1c, FPG and fasting SMPG reductions were also observed. Supported By: Sanofi
MON-LB120 MODY3 With Insulin Coding Gene Mutation and Craniofacial Microsomia: A Case Report
Authors: Cao Chenxiang , Han Xueyao , Ma Yumin , Bernet Victor Joseph , Xiao Jianzhong 
Published: May 2020

Abstract
Background: Maturity onset diabetes in young 3 (MODY 3) is caused by mutation of the hepatic nuclear factor 1 alpha (HNF-1A) gene. Craniofacial macrosomia (CFM) is associated with an abnormal development of craniofacial structures during the embryonic period. Maternal diabetes and genetic predisposition have been associated with CFM1. There are rare reports about an association of MODY 3 and CFM. Clinical case: An 11-year-old male patient presented with right side CFM (mild mandibular hypoplasia, internal auditory canal absence, severe pinna hypoplasia, abnormal orbital size and location, O3.M0.E3.N0.S02) noted at 8 months of age. Preoperative examination revealed A1c at 10.9%. After short term intensive insulin therapy, he had standard bread meal test: fasting glucose 8.11 mmol/L, insulin 13.9 mIU/L (3-25), C-peptide 1.25 ng/ml (0.81-3.85); 1 hour glucose 10.05 mmol/L, insulin 27 mIU/L, C-peptide 2.42 ng/ml; 2 hour glucose 8.17 mmol/L, insulin 16.09 mIU/L, C-peptide 2.11 ng/ml. GADA, IAA and ICA were negative. The mother was diagnosed diabetes at age 27years, when the patient was 8-month-old, and received insulin therapy. The mother was blind by age 35years due to diabetic retinopathy and died of DKA at 38-years-old. The patient’s 16-year-old brother had left side CFM (O2.M1.E2.N0.S0) and his OGTT was normal. The father was diagnosed with impaired glucose tolerance. The family had whole genome sequencing by Sanger technique, and resequenced the mutation with side primers. The CGA to CAA mutation was present at the 686 loci of exon 3 of HNF1A gene in the patient and mother. The HNF1A exon 3 mutation of CGA to CAA resulted in the change of arginine to glutamine which by the HGMA database is recognized as a reported MODY3 gene mutation. There was a mutation of G to A in the 4 loci of exon 1 of the insulin coding region in chromosome 11 in both the patient and elder brother. Neither elder brother nor father had the CGA mutation of HNF1A. Conclusion: There has not been a previous report of a relationship between HNF1A and CFM. In this case, the elder brother had CFM without a HNF1A mutation which does not support a connection between CFM and HNF1A. The two brothers both had CFM and insulin coding gene mutations which would represent a new association not previously described. Further testing is needed to confirm a relationship between the two. Reference: 1. Chen Q, Zhao Y, Shen G, Dai J. Etiology and Pathogenesis of Hemifacial Microsomia. J Dent Res 2018; 97(12): 1297-305. 2. Gougoutas AJ, Singh DJ, Low DW, Bartlett SP. Hemifacial microsomia: clinical features and pictographic representations of the OMENS classification system. Plast Reconstr Surg 2007; 120(7): 112e-20e.
SUN-LB137 Endocannabinoids Induce Endoplasmic Reticulum Stress in Hepatocytes and Human Coronary Artery Endothelial Cells
Authors: Richter Angela , Parekh Shrina , Kalidas Poonam Kirti , Haas Michael John , Mooradian Arshag D 
Published: May 2020

Abstract
Obesity and diabetes are important risk factors for the development of coronary heart disease and stroke. Plasma endocannabinoid (EC) levels are inappropriately elevated in obesity and diabetes, and are hypothesized to play a causal role in central regulation of weight gain. Importantly, it was recently demonstrated that cannabinoid receptor 1 (CNR1) triggers cell stress and induces apoptosis in kidney tubule cells exposed to palmitic acid and high-glucose (HG). HepG2 and human coronary artery endothelial cells (HCAEC) were treated with tunicamycin (TM), thapsigargin (TG), high-glucose (HG), anandamide (AN), and 2-arachondonyl glycerol (2-AG), and endoplasmic reticulum (ER) stress was measured. In cells treated with TM, AM, and 2-AG and the UPR inhibitors 4-phenylbutyrate (4-PB) and taurodeoxycholic acid (TUDCA), both 4-PB and TUDCA prevented AN and 2-AG from promoting ER stress. ER stress in cells treated with AN and 2-AG, but not TM, was inhibited by the CNR1 antagonist rimonabant. Similar results were obtained with HCAEC. Furthermore, treatment with AN and 2-AG induced inositol requiring enzyme 1α and protein kinase R-like endoplasmic reticulum kinase phosphorylation but had no effect on their expression, while activating transcription factor 6 and binding immunoglobulin protein expression were also induced by AN and 2-AG in both HepG2 and HCAEC. Finally, AN and 2-AG treatment induced CNR1 expression in both cell lines. These results strongly suggest that EC’s promote ER stress and potentially induce liver and endothelial cell dysfunction.
SAT-LB311 Inoperable, Metastatic Pheochromocytoma & Paraganglioma Tumor Size Reduction After Lu-177-dotatate (Lutathera®) Treatment Trial: The Role of Nursing
Authors: Ude Assumpta , Frank Lin , Pacak Karel , Demissie Ejigayehu 
Published: May 2020

Abstract
Tumor Size Reduction after Lu-177-DOTATATE (Lutathera®) Treatment in Patients with Inoperable Metastatic Pheochromocytoma and Paraganglioma: The Role of NursingAssumpta Ude, Frank I. Lin, Karel Pacak, Ejigayehu Demissie. Clinical Center Nursing Department, Molecular Imaging Program NCI, Endocrine Service Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development. Background: Nursing management of patients with metastatic pheochromocytoma (PCC) and paraganglioma (PGL) undergoing treatment trial with radiopharmaceutical medication has unpredictable clinical outcomes. Clinical Case: A 52-year old woman with inoperable metastatic PCC/PGL was admitted into protocol 17-C-0087 after poor response to various chemotherapies. Patient was treated in the endocrine nursing unit with 200 mCi of Lu-177-DOTATATE (Lutathera®) intravenous infusion given by a radionuclide specialist every eight weeks for a total of four doses. Prior to admission, various members of the endocrine clinical nursing leadership team reviewed protocol with the medical and radiation safety team and a clinical research nurse (CRN) to ensure CRNs understand their roles and expectations to ensure patient safety during procedures and treatment. The patient was admitted on the day preceding the treatment and monitored for 48 hours afterwards. The CRN obtained comprehensive diet and medication history to determine if there is anything that may falsely elevate plasma/urinary catecholamines/metanephrines. The CRN ensured correct placement of intravenous (IV) line and proper collection of blood from IV line to increase the reliability of results. The CRN ensured that IV amino acid (Clinisol 15 %) infusion was administered 30 minutes prior to dosing to diminish renal issues. This patient had minimal side effects and no adverse events to therapy. The research team followed up the patient in clinic every month while she was on treatment, then every 3 months in the follow-up period. Recent evaluation showed this patient had stable vital signs, impalpable supraclavicular lymph node, returned to baseline physical activity with significant decrease in the size of the PCC/PGL, and reduction in serum catecholamine/metanephrine levels. Conclusion: The endocrine CRN team is critical in the assessment, monitoring, observation and education of patients and families regarding expectations during therapy which played a significant role in minimizing the patient’s side effects to therapy. Working collaboratively with other members of the multidisciplinary research team also contributed to patient’s favorable outcome.
SAT-LB56 Undernutrition Reduces Transcript Abundance of Kisspeptin and Neurokinin B in Young Male Sheep
Authors: Shuping Sydney L , Renwick Allison N , Harlow Lynn , Sommer Jeffrey R , Merkley Christina M , Nestor Casey 
Published: May 2020

Abstract
Proper energy balance is important to ensure reproductive success. Chronic nutrient restriction is known to suppress hypothalamic-pituitary function, but the central mechanisms whereby undernutrition inhibits GnRH/LH secretion remain largely unknown. KNDy neurons, which co-express kisspeptin, neurokinin B (NKB), and dynorphin, form a unique population of cells in the arcuate nucleus (ARC) of the hypothalamus and play a critical role in GnRH/LH pulse generation. Based on recent evidence from our lab that chronic feed restriction reduces kisspeptin and NKB protein expression in young male sheep, we hypothesized that nutrient restriction would inhibit mRNA abundance for kisspeptin and NKB in the same animals. Fourteen wethers were placed into a fed to maintain body weight group (n=6; Fed) or a feed-restricted to lose 15-20% of pre-study body weight group (FR; n=8). Weekly blood samples (every 12 minutes for 4.5 hours) were taken via jugular venipuncture and plasma was stored at -20°C until the time of radioimmunoassay. Weekly body weights were recorded and feed amounts were adjusted to achieve desired body weights. At Week 13, animals were euthanized following blood collection, brain tissue was perfused with 4% paraformaldehyde, and tissue containing the hypothalamus was collected. Following submersion in 20% sucrose for at least four weeks, hypothalamic blocks were sectioned at 50 µm on a freezing microtome, and stored in a cryopreservative solution until processing. At Week 13, the average percent change in body weight was clearly evident (Fed, 6.79 + 3.4% vs FR, -19.82 ± 1.6%), and mean LH was significantly lower in FR wethers (13.41 + 3.7 ng/ml) compared to Fed controls (26.43 + 2.5 ng/ml). To assess changes in mRNA abundance, we used a relatively new in situ hybridization technique, RNAscope, to quantify mRNA for kisspeptin and NKB in the ARC with probes that were ovine-specific. Results showed that feed restriction reduced the number of kisspeptin mRNA-expressing cells (Fed, 231.2 + 14.4 vs FR, 100.3 + 35.9) and NKB mRNA-expressing cells (Fed, 192.7 + 18.4 vs FR, 97.3 + 21.7) per hemi-section. Furthermore, analysis of kisspeptin and NKB co-expressing cells (30 cells/animal) revealed that feed restriction significantly reduced the average mRNA integrated density for NKB, but not kisspeptin, compared to Fed controls. Together, these findings further support a role for kisspeptin and NKB in the central mechanism governing GnRH/LH secretion during undernutrition in male sheep.
SAT-LB120 A Software Application Delivering Behavioral Therapy Improved Glycemic Control in Adults With Type 2 Diabetes
Authors: Guthrie Nicole L , Appelbaum Kevin J , Berman Mark A 
Published: May 2020

Abstract
Despite advances in pharmacological treatment, half of U.S. patients with type 2 diabetes are not achieving glycemic control (1). Even when glycemic control is achieved via pharmacotherapy, a substantial residual risk to all-cause mortality still exists (2). An overlooked contributor to both poor glycemic control and mortality risk is the need to address the behavioral determinants of type 2 diabetes. We tested a novel software application (app) designed to change behaviors that are root causes of type 2 diabetes and improve glycemic control. If behavioral therapy is effective and can be delivered using software installed on a patient’s smartphone, it may provide a cost-effective means of improving outcomes in this patient population. To study this hypothesis, we examined data from app users with suboptimal glycemic control, as defined by having a 3-day average of self-reported fasting blood glucose (FBG) values ≥ 152 mg/dL, who used the app for 12 weeks. 74 participants residing in 32 U.S. states met inclusion criteria. Their baseline characteristics (means±SD) were an age of 55.2±7.0 years, body mass index 34.7±7.9 kg/m2, 71.6% (53/74) female, current use of 2.2±0.9 antihyperglycemic medications, FBG 199.4±45.1 mg/dL and 10.6±7.1 years since diagnosis of type 2 diabetes. Change in FBG was calculated as the difference between 3-day averages anchored by the first and last values reported. Mean change in FBG was -22.9±42.0 mg/dL (P=0.001, using paired t-test) with an average of 69.0±29.9 days between the first and last value reported. Participants reported an average of 4.4±1.7 FBG values each week over 12-weeks. Participants used the app on average 4.6±1.8 days each week and spent 5.6±8.3 minutes each use. We performed a tertile analysis to examine the relationship between degree of behavioral therapy use and change in glycemic status. The mean changes in FBG in the lowest to highest tertile of behavioral therapy use were -14.4±39.2, -20.4±47.6 and -32.9±38.4 mg/dL (P=0.06, comparing lowest to highest tertile, using a pairwise comparison of the least squares means accounting for baseline FBG and years since diagnosis). These results suggest use of this novel software application is associated with meaningful improvements in glycemic control in a widely distributed treatment population and warrants further study.
Refs: (1) Edelman et al., Diabetes Care 2017 Nov; 40(11): 1425-1432. (2) Rodríguez-Gutiérrez et al., Circ Cardiovasc Qual Outcomes. 2016; 9:504-512.
MON-LB119 Euglycemic Diabetic Ketoacidosis in a Patient on Canagliflozin Presenting With Hypoglycemia
Authors: Inkollu Sindhura , Korem Sindhuja , Ganne Sudha 
Published: May 2020

Abstract
Background: Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newer class of antihyperglycemics that cause reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. Common side effects include yeast and urinary tract infections. The US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors. The mechanisms by which SGLT2 inhibitors cause euglycemic DKA are unclear. SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin and an increase in glucagon production.1 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA. Here, we report a case of euglycemic DKA in a patient on Canagliflozin who presented initially with hypoglycemia.
Clinical case: A 70 year old female presented with altered mental status for 1 day duration. Her past medical history is significant for type 2 Diabetes Mellitus, being managed on Canagliflozin, Glimepiride and Janumet. One week prior to admission she had lumbar spinal fusion surgery. Since then she has been feeling weak and tired with poor oral intake, but continued to use her medications. Initial laboratory findings showed blood glucose of 68 (70-100 mg/dl) without any acidosis. Her altered mental status was attributed to higher opioid doses which she received prior. Oral hypoglycemic agents have been held. On 2nd day of hospitalization, patient became more lethargic and complained of nausea. Laboratory testing revealed a serum glucose of 250mg/dL, serum bicarbonate of 13 (21–31mmol/L), and Anion gap of 25 (3.6–11.0mmol/L). With the suspicion of DKA, a beta-hydroxy butyrate level was obtained which was elevated at 90.10 (0 – 4.16 mg/dL). Venous blood gas analysis was significant for pH 7.23 (7.31-7.41) and pCO2 – 28 (41-51 mmHg). Urinalysis showed ketosis and glucosuria. Patient was diagnosed as euglycemic diabetic ketoacidosis from Canagliflozin in presence of precipitating factors - stress and poor intake. Patient was treated with insulin drip and intravenous fluids with reduction in anion gap and correction of acidosis within 24hrs. There was a gradual improvement in her mental status. She was discharged on subcutaneous insulin, and all other diabetic medications were stopped.
Conclusion: Our case highlights the importance of being vigilant in a patient on Canagliflozin, euglycemic DKA can occur even if they present initially with hypoglycemia and no acidosis.
Reference: 1. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7(2):135-138.
MON-LB302 Evaluating the Impact of a New Intake Process for British Columbia Children’s Hospital Gender Clinic
Authors: Fox Danya A , Tan Mabel , Lalani Robyn , Atkinson Louanna , Hursh Brenden , Metzger Daniel L 
Published: May 2020

Abstract
Our pediatric Gender Clinic is receiving a growing number of referrals, yet continues to operate with limited resources. To try to address this issue, a new clinical pathway was developed in 2017, which included an inter-professional assessment clinic run by nurses and social workers as the entry point for new referrals (known as ‘intake appointments’). These visits help to identify those youth who require urgent access to care (i.e. for imminent puberty), wayfinding to community supports and providers who can complete GnRH analog and hormone-readiness assessments, and information about potential medical interventions. The goals of this study were to (1) map out current processes, (2) evaluate wait times for patients referred in 2015-2016 (pre-intake) and 2018-2019 (post-intake), and (3) describe referral patterns and outcomes. Patients referred in 2017 were excluded, as this was a transitional year. In 2015-2016, 222 referrals were received, compared to 407 referrals in 2018-2019. Of the post-intake cohort, to date, 202/407 referrals have led to an intake appointment, of which 45 were via telehealth (a service not previously offered to families). Average wait time to physician visit was 171 days (range 10-1271; IQR 69-208) for patients in the pre-intake cohort, while the average wait time to intake appointment was 200 days (range 9-569, IQR 114-242) in the post-intake cohort. Wait time to physician visits cannot be assessed yet, due to the number of pending referrals. Fifty-four referrals were cancelled in the pre-intake, and 73 in the post-intake cohort. In both groups, the primary reason for cancellation was redirection by our team to other services (32% in both groups), and the second most common reason was cancellation by the family/no show to appointment (26% and 22% in the pre- and post-intake cohorts, respectively). Staffing resources and number of clinics per week have changed over the years, limiting our ability to attribute changes directly to the new clinical pathway. Moreover, most hormone-readiness assessments are completed by community providers. Therefore, wait times to physician visits partly reflect difficulty in accessing these community resources. However, using our new model of care, we have engaged with hundreds of patients and families within a similar time frame to the 2015-2016 cohort, despite an almost doubling of the number of referrals received by our clinic. Although these initial visits do not allow for initiation of medical therapy, they are a means to support patients and families through their gender journey. Moreover, the intake appointments have promoted inter-professional collaborative care, which is particularly beneficial in the face of limited resources. Thus, we believe this new model of care has led to improved quality of care for patients accessing our Gender Clinic.