bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-681 Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation
Authors: Ahn Moon Bae , Lee Yoon Ji , Lee Na Yeong , Kim Seul Ki , Kim Shin Hee , Cho Won Kyoung , Cho Kyoung Soon , Jung Min Ho , Suh Byung Kyu
Published: May 2020

Background: Neonatal diabetes mellitus (NDM) occurs within the first 6 months of life. Advances in molecular genetics have identified various causatives genes. Mutations in EIF2AK3 causes Wolcott-Rallison syndrome characterized by NDM, multiple epiphyseal dysphasia and growth retardation. PTF1A is associated with the development of pancreas and cerebellum. Both EIF2AK3 and PTF1A mutations are causative genes for permanent NDM with spontaneous and autosomal recessive inheritance. We report a neonate with transient NDM with both EIF2AK3 and PTF1A variants confirmed by Sanger sequencing where each parent found to be a heterozygous carrier of each mutation. Case presentation: A two-day old boy was transferred from a local hospital due to hyperglycemia (blood glucose of 385 mg/dL) and glycosuria. Serum c-peptide (0.06 ng/mL) and insulin (0.64 μU/mL) were low. The patient did not present sings of ketoacidosis and was screened negative for pancreatic autoantibodies. The patient did not have any family history of diabetes. Molecular genetic analysis was performed and continuous infusion of intravenous insulin with pre-prandial bolus was started. Oral sulfonylurea therapy was attempted to prevent adverse neurocognitive outcome however, it showed no response and unable to stabilize blood glucose level. Targeted panel sequencing identified two different novel variants: a heterozygous missense mutation (c.3272G>T) in exon 17 of EIF2AK3 gene and heterozygous missense mutation (c.53C > T) in exon 1 of PTF1A gene; both of which have not been previously reported and were no likely pathogenic variants. The patient’s father confirmed to be heterozygous carriers of the EIF2AK3 mutation while mother being heterozygous carriers of the PTF1A mutation. Blood glucose level gradually began to stabilize with insulin therapy, and upon discharge the patient switched to continuous subcutaneous insulin infusion (pump) with continuous glucose monitoring. Conclusions: NDM caused by in combination of EIF2AK3 and PTF1A gene mutation is a rare condition and could resemble the disease progress of transient form of NDM. Although hyperglycemia might not be an issue of lifelong period, early genetic screening and prompt insulin initiation with consistent glucose monitoring are able to prevent further diabetic complications. In addition, the result of genetic testing in our patient raises the possibility of NDM as polygenic form of diabetes.
MON-192 Comparison of the Seated and Recumbent Saline Infusion Test for the Diagnosis of Primary Aldosteronism in Chinese Population
Authors: Zhang Dan , Chen Tao , Tian Haoming , Li Yuanmei , Mo Dan , Zhang Tingting , Wang Wen , Zhang Guofu , Liu Yuping , Tang Lizhi , Zhu Yuchun , Yang Ling , Yang Ling , Ren Yan
Published: May 2020

Background:

None of the diagnostic tests for primary aldosteronism (PA) are ideal according to the current literature. In a preliminary study, the seated saline infusion test (SSIT) was more sensitive than the recumbent saline infusion test (RSIT) for the diagnosis and subtype classification of PA. However, it is unclear whether the SSIT is suitable for Chinese PA patients.

Objective:

We prospectively investigated the accuracy of the seated saline infusion test (SSIT) in 113 patients with hypertension (including 93 PA and 20 essential hypertension (EH) patients) in the Department of Endocrinology and Metabolism.

Approach and Results:

Each patient underwent an recumbent saline infusion test (RSIT) and seated saline infusion test (SSIT). The accuracy of the SSIT for a confirmative primary aldosteronism (PA) diagnosis and subtype classification was evaluated and compared with the RSIT. The area under the receiver operating characteristic (ROC) curve (AUC) of aldosterone for the SSIT was significantly greater than that for the RSIT (0.945±0.0199 vs 0.828±0.0404; P<0.05). The ROC analysis showed that the optimal plasma aldosterone cutoff values were 12.94 ng/dl for the SSIT (sensitivity 86.02%, specificity 95%; Youden index (YI)=0.810) and 12.04 ng/dl for the RSIT (sensitivity 83.15%, specificity 57%; Youden index (YI)=0.401). The optimal aldosterone concentration cutoff value for classifying aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was 18.12 ng/dl for the SSIT (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSIT.

Conclusions:

The SSIT was safe and convenient for PA diagnosis. The accuracy of the SSIT for a confirmatory diagnosis of PA was better than that of the RSIT. The SSIT is a reliable alternative for PA confirmation in Chinese individuals.
OR01-03 Thyroid Receptor Alpha Interacts with COUP-TFII in the Regulation of Postnatal Skeletal Muscle Regeneration
Authors: Aguiari Paola , Petrosyan Astgik , Liu Yan-Yun , Cheng Sheue-Yann , Perin Laura , Brent Gregory A , Milanesi Anna
Published: May 2020

Myopathic changes, including muscular dystrophy and weakness, are commonly described in hypothyroid and hyperthyroid patients. Thyroid hormone signaling, via activation of thyroid nuclear receptors (TRs), plays an essential role in the maintenance of muscle mass, function, and regeneration. TRs are ligand-inducible transcription factors expressed in almost all tissues, including skeletal muscle. In a mouse model of Resistance to Thyroid Hormone carrying a frame-shift mutation in the TRα gene (TRα1PV)1,2 we observed skeletal muscle loss with aging and impaired skeletal muscle regeneration after injury. We recently described that TRα interacts with the nuclear orphan receptor Chicken Ovalbumin Upstream Promoter-factor II (COUP-TFII, or NR2F2), which is known to regulate myogenesis negatively and has a role in Duchenne-like Muscular Dystrophies3. We showed that COUP-TFII expression declines with age in WT mice, while the skeletal muscle of TRα1PV mice shows a sustained significantly higher expression of COUP-TFII. Our findings suggest that the TRα/COUP-TFII interaction might mediate the impaired skeletal muscle phenotype observed in TRα1PV mice. To better characterize this interaction, we isolated SC from 10 months old WT and TRα1PV mice and cultured them in vitro using novel methods established within our lab. Using siRNA probes, we next silenced COUP-TFII and characterized the cells via RNA-seq analysis. In vitro, we assessed myoblast differentiation and proliferation using differentiation assays and EdU incorporation. We observed that satellite cells from TRα1PV mice display impaired myoblast proliferation and in vitro myogenic differentiation compared to WT SCs. However, when COUP-TFII was silenced, the myogenic potential of TRα1PV satellite cells was restored, with a higher proliferation of myoblasts and a higher number of fully differentiated myotubes after 4 days of myogenic induction. RNAseq analysis on satellite cells from TRα1PV mice after COUP-TFII knockdown showed upregulation of genes involved in the myogenic pathway, such as Myod1 and Pax7, and of genes in the thyroid hormone signaling, such as Dio2. Ingenuity Pathway Analysis further showed activation of pathways regarding cell growth, differentiation, matrix remodeling along with muscle function, muscle contractility, and muscle contraction. These in vitro results suggest that by silencing COUP-TFII we promote the myogenic pathway and may further rescue the impaired phenotype of TRα1PV mice. These studies can help increase our knowledge of the mechanisms involved in thyroid hormone signaling in skeletal muscle regeneration, which will ultimately increase the possibility of designing more specific treatments for patients with thyroid hormone-induced myopathies. References: 1Milanesi, A., et al, Endocrinology 2016; 2Kaneshige, M. et al, Proc Natl Acad Sci U S 2001; 3Lee HJ, et al, Sci Rep. 2017.
MON-396 A Critical Review of the Assessment of Vitamin D Status
Authors: Chausmer Arthur B
Published: May 2020

In the United State the evaluation of osteoporosis frequently includes an assessment of vitamin D status. Most often this is done by evaluation of the serum 25 hydroxycalciferol (25 OHD) level. The reasons for this are not entirely clear since D deficiency is characterized by osteomalacia, pathologically very different from osteoporosis. Presumably the reason is to assess the adequacy of calcium absorption across the gastrointestinal mucosa so as to provide sufficient substrate to the osteoid for bone mineralization. If this is the case, the best assessment of D status should be the active metabolite, 1,25 dihydroxycalciferol, (1,25 OH2 D), not an inactive intermediate, such as 25 OHD. The use of an inexact test results in increased cost for less reliable data and supports factitious deficiency with unnecessary and potentially dangerous treatment. The most often quoted reason for not using the 1,25 OH2 D is the short half life. This neglects the fact that half life is not relevant to substances in equilibrium and that the circulating half life does not necessarily reflect the physiologic half life. Equally important, the 25 OHD as a marker of D status is variable due to, among others, drug metabolites affecting hepatic 25 hydroxylases, hepatic function in general, and differences in the activation of of 25 D related to renal function. Additionally, there is virtually no data about the whole body load for any metabolite in the D pathway, so there is no way of actually assessing whether stores are replete or not. While there are several studies suggesting 25 OHD is only a marginal indicator of D status, primarily in the extreme deficiency states which generally rare in the United States. Well controlled studies of the efficacy of 1,25 OH2 D in the assessment of D status are few for many reasons, most prominently cost and lack of sponsor interest. In the absence of such data, one must rely on basic physiologic principals which strongly suggest abandoning the use of the 25 OH D level as an indicator of vitamin D status and, perhaps, using the 1,25 OH2 D to assess D status.
MON-344 Uncommon Etiology of Hypophosphatemia and Secondary Hyperparathyroidism: Ferric Carboxymaltose Infusion
Authors: Sever Sakine
Published: May 2020

Background: Hypophosphatemia has been recognized as one of the side effect of intravenous ferric carboxymaltose infusion. This effect is thought to be secondary to fibroblast growth factor 23 (FGF 23) mediated renal phosphate wasting and associated with calcitriol deficiency and secondary hyperparathyroidism.

Clinical Case: A 76 years old male patient with medical problems including hypertension, type 2 diabetes mellitus, hyperlipidemia, paroxysmal atrial fibrillation, nephrolithiasis, spinal stenosis and chronic anemia was referred to endocrinology clinic for osteoporosis management. Bone density scan showed left femur neck T-score of -2.5 and L1-L4 lumbar spine T-score of 1.4. He reported pain on back and bilateral posterior thighs, difficulty with ambulation which were partly attributed to severe spinal stenosis that he was planned to have surgery for. Muscle strength was normal on examination. Laboratory studies were obtained for osteoporosis work up and showed: Calcium: 8.9 mg/dL (8.8-10.2 mg/dL), Creatinine: 0.77 mg/dL (0.74-1.35 mg/dL), GFR: 88 mL/min/BSA, Albumin 4.5 g/dL (3.5-5.0 g/dL), 25-Hydroxy vitamin D: 26 ng/mL, Magnesium 1.8 mg/dL (1.7-2.3 mg/mL), 1,25 Dihydroxy Vitamin D 24 pg/mL (18-64 pg/mL), Phosphorus: 1 mg/dL (2.5-4.5 mg/dL), PTH 163 pg/mL (15-65 pg/mL), Hemoglobin 12.9 mg/dL (13.2-16.6 mg/dL). Due to hypophosphatemia tumor induced osteomalacia diagnosis was entertained and further work up was considered in this regard however later noted that patient received ferric carboxymaltose 750 mg infusion two times within last 3 weeks for iron deficiency anemia. Hemoglobin level was 8.6 mg/dL before the infusions. After oral phosphate replacement the phosphate level improved to 2.4 mg/dL. Serum FGF 23 level was measured and it was normal at 108 RU/mL (<180 RU/mL). He was then started on bisphosphonate treatment for osteoporosis.

Conclusion: Hypophosphatemia and secondary hyperparathyroidism can be seen after ferric carboxymaltose infusion due to FGF-23 mediated mechanism. In literature various presentations were reported from transient- asymptomatic hypophosphatemia to severe acute symptomatic hypophosphatemia along with persistent hypophosphatemia with osteomalacia and fragility fractures due to recurrent ferric carboxymaltose infusions. Thus, one should keep this possible side effect in mind during evaluation of hypophosphatemia and osteoporosis.

References: 1. Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. Dec 6 2018;3(23):e124486 2. Fang W, McMahon LP, Bloom S, Garg M. Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose. JGH Open. October 2019, volume 3, issue 5, P 438-440
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

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 >200 U/day, BMI, and age >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

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

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

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 >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 >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 >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 <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

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

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 > 9, 24.0% with carotid atherosclerosis defined by CIMT > 0.07 mm or presenting of carotid plague and 8.3% with ABI < 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<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<0.01. ROC analysis revealed that ADVANCE > 3.0% in 4-year, UKPDS > 11% in 10-year, fatal-SCORE > 6% in 10-year and FRS > 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

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

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

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.
SAT-045 Free Testosterone and Cardiometabolic Parameters in Adult Men - Comparison of Algorithms for Calculation of Serum Free Testosterone
Authors: Holmboe Stine Agergaard , Jasuja Ravi , Priskorn Laerke , Jørgensen Niels , Juul Anders , Andersson Anna-Maria
Published: May 2020

Context. Determining the free or bioavailable testosterone level has gained increasing interest over the years and different indirect algorithms have been suggested.

Objective. To compare commonly used algorithms of calculation of serum free testosterone, specifically free androgen index (FAI), free testosterone estimated using the Vermeulen algorithm (cFTV) and the Zakharov algorithm (cFTZ) as well as total testosterone in relation to baseline and long-term cardiometabolic conditions.

Design. A prospective cohort study of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters.

Setting and Participants. 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated.

Main Outcome Measures. Baseline cardiometabolic parameters and follow-up information on type 2 diabetes, ischemic heart disease, cardiovascular disease mortality, and all-cause mortality.

Results. Free testosterone levels calculated according to the two algorithms differed systematically but however correlated well (cFTV vs. cFTZ: r=0.9, p<0.01) and the relative standard deviations ranged from 37% to 41%. In general, men having cardiometabolic conditions at baseline had lower absolute levels of FAI, cFTV and cFTZ. However, when age-standardizing the hormone levels, FAI levels were higher in this group of men whereas cFTV and cFTZ remained lower compared to men without these conditions. The associations seen for cFTV and cFTZ were in line with the association seen for total testosterone. Cox proportional hazard models revealed that men in the highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR=0.74 (0.49-1.10), cFTZ: HR=0.59 (0.39-0.91)) than men in the lowest quartile. In contrast, men with highest levels of FAI had a 74% increased risk of developing type 2 diabetes compared to men in the lowest quartile (HR=1.74, 95% CI:1.17-2.59). In relation to all-cause mortality, FAI showed the strongest inverse association followed by cFTV, whereas cFTZ and total testosterone did not show any association.

Conclusion. Free testosterone estimated by the Vermeulen and Zakharov algorithms differed systematically. However, the computed values correlated well and showed similar associations to baseline and long-term cardiometabolic parameters; albeit with subtle differences. In contrast, an empiric ratio, FAI showed opposite associations to several of the examined parameters and may reflect limited clinical utility.
SUN-584 Micrornas in Brown and White Adipocytes
Authors: Dimitri Federica , Alam Mohammad T , Dib Lea , Christian Mark
Published: May 2020

Two types of adipose tissue exist: white (WAT) and brown (BAT). WAT stores energy while BAT consumes fatty acids and produces heat by non-shivering thermogenesis through Uncoupling Protein 1 (UCP1). BAT and WAT cooperate in maintaining energy homeostasis balance. Understanding their physiology is important for the development of treatments against diseases where this equilibrium is compromised, such as obesity and associated metabolic disorders. MicroRNAs (miRNAs) are potent gene regulators and an increasing body of evidence suggests their involvement in adipogenesis and adipose metabolism. MiRNAs can also be secreted into the extracellular environment and be taken up by distal cells, mediating cell-to-cell communication. However, very little is known about adipose tissue-derived circulating miRNAs. Through miRNA PCR array analysis we identified several miRNAs that are differentially secreted among undifferentiated and differentiated brown and white adipocytes, such as miR-196a, 378a-3p and miR-138-5p. Bioinformatics target prediction revealed that these miRNAs are potentially involved in important processes regulating the functioning of adipose tissue and its cross-talk with distal cells. Among the predicted targets of miR-196a, we identified ADAM10 (A Disintegrin And Metalloproteinase Domain-containing protein 10). This protein is responsible for the proteolytic release of several cell-surface proteins involved in numerous biological processes such as inflammation and its role could be of relevant importance in the physiopathology of the adipose tissues.
MON-694 EDKA and MALA in the Setting of Severe Heart Failure and Acute Renal Failure, Due to SGLT2-i
Authors: Heckart Jonathan Calvin , Shaw Michael
Published: May 2020

Background: EDKA is a reported potential side effect of SGLT-2i that presents a unique challenge for diagnosis and management in the setting of HF and concurrent AKI. Literature encourages wide use of SGLT-2i’s, however this case demonstrates the need of proper evaluation before initiating therapy.

Case: A 53 year old male with PMH of T2DM, Atrial fibrillation, HFrEF, presented to the Emergency Dept after a week of confusion, nausea, vomiting, and diarrhea. These symptoms were presumed due to gastroenteritis and our patient continued working on his farm in the summer heat. Following 3 days of intractable vomiting, he began to develop confusion, took his medications and presented to the ED. He was on metformin and had recently started empagliflozin following a heart failure exacerbation. Upon arrival the patient was noted to have a severe AKI with Cr of 15, hyperkalemia with potassium of 7.7, Anion gap of 45, bicarbonate of 4. Lactic acid was noted to be 7.7 and BHB was later noted to be 10.5 with a serum blood glucose of 155.

Pt was determined to have Euglycemic Diabetic Ketoacidosis with an additional Metformin associated lactic acidosis. He was started on an insulin drip with a concurrent D20 infusion to minimize fluid intake. Dextrose was titrated up to maintain a goal BG of 150-180 while on a stable insulin rate of 5u/hour, while monitoring serum ketones to resolution of DKA. Due to excess fluid intake he required intubation and later, hemodialysis due to metformin associated lactic acidosis and acute renal failure. Following 3 days of dialysis he was able to successfully wean from vent and pressors, making a complete recovery.

Conclusion:

We present a patient with EDKA likely resulting from dehydration induced AKI compounded by SGLT2i induced diuresis. As he developed his kidney injury, metformin was able to build up to toxic levels inducing lactic acidosis. Treatment in this patient was based on the underlying physiology providing glucose to allow resolution of ketosis. Treatment is not well studied, but given the origin of the pathology should resemble a standard DKA protocol with glucose repletion. SGLT2i and metformin combinations have shown an increased risk of metabolic acidosis1 and lactic acidosis2. This case highlights a potential risk of the combination in the setting of renal insufficiency and tenuous fluid states.

References:

(1) Donnan, Katherine, and Lakshman Segar. “SGLT2 Inhibitors and Metformin: Dual Antihyperglycemic Therapy and the Risk of Metabolic Acidosis in Type 2 Diabetes.” European Journal of Pharmacology, U.S. National Library of Medicine, 5 Mar. 2019.

(2) Schwetz V, Eisner F, Schilcher G, et al. Combined metformin-associated lactic acidosis and euglycemic ketoacidosis. Wien Klin Wochenschr. 2017;129(17-18):646–649. doi:10.1007/s00508-017-1251-6
SAT-633 Features of Vitamin B12 and Vitamin D Homeostasis in Patients with Type 2 Diabetes Mellitus Associated with Tuberculosis
Authors: Khalimova Zamira Yusufovna , Kholmatova Gulkhae Azimjonovna
Published: May 2020

The aim of the study was to study the features of homeostasis of vitamin B12 and vitamin D deficiency in patients with type 2 diabetes mellitus (T2DM) associated with tuberculosis.

Material and research methods. Under our supervision, there were 48 patients who were divided into 2 groups: group 1 - these are patients with type 2 diabetes associated with tuberculosis, who made up the main group (n = 42), group 2 - this is the control group represented by patients with tuberculosis (n = 12)

Research methods included general clinical, biochemical (glucose, glycated hemoglobin, coagulogram, lipid spectrum, etc.), hormonal (insulin. C-peptide) blood and urine tests. The content of vitamin B12 and vitamin D was studied in patients of both groups. Instrumental studies included ECG, dopplerography of the great vessels, ultrasound of the internal organs, and x-ray studies.

The results of the study. The first group consisted of 17 men and 19 women, whose average age was 54.4 ± 2.2 / 55.5 ± 1.7 (m / f), respectively. The duration of diabetes in men was within 6.8 ± 1.4 years, and in women 4.6 ± 0.7 years. The duration of tuberculosis in men was 1.8 ± 0.3, and in women 1.9 ± 0.2 years.

The average HbA1C content was in the range of 8.9 ± 0.50 / 9.9 ± 0.51, and glucose 10.6 ± 0.61 / 15.0 ± 0.82 nmol / L in patients of the 1st group. The average insulin level was 11.3 ± 2.09 / 11.7 ± 2.2 pg / ml, and Vit B12 403 ± 33.7 / 407 ± 45.7 (normal 193-982 pg / ml, on average 450 pg / ml), the content of vit D was in the range of 13.1 ± 2.1 / 11.1 ± 3.08 ng / ml, respectively (normally from 30-100 ng / ml).

The second group consisted of 9 men and 3 women, the average age was 49.5 ± 5.2 / 45.0 ± 8.0 years. The duration of tuberculosis in this group was 1.8 ± 0.4 / 1.0 ± 0.2 years. The average content of HbA1C was in the range of 4.1 ± 0.2 / 4.9 ± 0.7, and glucose 5.1 ± 0.1 / 5.8 ± 0.4 nmol / L in patients of the 1st group. The average insulin level was 9.6 ± 1.9 / 16.3 ± 1.3 pg / ml, and Vit B12 376.7 ± 91.1 / 402.0 ± 13.3 (normal, 193-982 pg / ml, average 450 pg / ml), the content of Vit D was in the range of 14.5 ± 1.4 / 11.6 ± 1.7 ng / ml, respectively (normally from 30-100 ng / ml).

Conclusions. In both groups of patients, the average content of vitamin D in the blood was significantly reduced (p <0.001), while the average levels of vitamin B12 in both groups were within normal limits, remaining below average normal values.