bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSUN305 A Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HM15136 in Obese or Overweight Subjects with Co-morbidities
Authors: Shin Wonjung , Choi JaeDuk , Yun Hyori , Han OakPil , Cho Hyungjin , Hompesch Marcus , Baek Seungjae 
Published: November 2022

Abstract
HM15136 is a novel long-acting glucagon analogue with an extended half-life. In vivo efficacy studies of HM15136 in animal models showed its therapeutic potential in obesity, and treatment requiring hypoglycemia. We enrolled an obese and overweight subjects without diabetes (study Part 1) and with diabetes (study Part 2) in a randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics, and pharmacodynamics of multiple subcutaneous doses of HM15136 for 12 weeks (NCT04167553). In Part 1, a total of 36 non-diabetic subjects randomly received HM15136 or its matching placebo in a ratio of 9: 3 in 3 cohorts (0.02, 0.04, and 0.06 mg/kg). The baseline mean age was 37.5 years, BMI was 33.9 kg/m2, and Fasting Plasma Glucose (FPG) was 92.3 mg/dL. The FPG increased with escalating doses of HM15136. The mean (SD) changes from baseline in FPG at week 12 were -1.0 (13.0) mg/dL for 0.02 mg/kg, 12.0 (10.7) mg/dL for 0.04 mg/kg, 17.9 (16.9) mg/dL for 0.06 mg/kg vs. 0.6 (6.5) mg/dL for placebo group. The FPG had returned to baseline at 3 weeks after study drug discontinuation. The presence of Anti-Drug Antibodies (ADAs) was confirmed in 5 subjects (18.5%) but dose-dependency was not observed. One (1) out of 5 ADA positive subjects had neutralizing ADA activity with no cross reactivity to endogenous glucagon. The most frequent Treatment Related Adverse Event (TRAE) was injection site erythema (11.1%), the frequency of TRAEs was not dose dependent. Throughout Part 1 and Part 2, all TRAEs were mild except for moderate hyperglycemia in patients with diabetes. Part 2 was completed earlier than planned due to the impact of COVID-19 and discontinued subjects due to the hyperglycemia. Part 2 was not included in this presentation because the interpretability of the data was limited. In conclusion, HM15136 was safe and well tolerated in non-diabetic obese subjects during the 12-week treatment at various dose levels. Treatment with HM15136 showed a dose dependent blood glucose increase. These results suggest future development opportunities for the management of treatment requiring hypoglycemia. A phase 2, Proof-of-Concept study in patients with congenital hyperinsulinism is currently ongoing (NCT04732416).
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN314 Severe Insulin Resistance Impacts the Growth Hormone-Insulin-Like Growth Factor-I Axis and Linear Growth
Authors: Okawa Marinna 
Published: November 2022

Abstract
Diabetes and insulin resistance (IR) may impact growth hormone (GH), insulin-like growth factor 1 (IGF-1), and linear growth. Poorly controlled diabetes impairs growth, while high insulin may increase growth.
To understand relationships between diabetes, IR, and growth, we examine height, body mass index (BMI), glucose, GH, and IGF- in patient populations with IR, including (in order of increasing IR): congenital generalized lipodystrophy (CGL), heterozygous pathogenic variants of the insulin receptor INSR (+/-), homozygous INSR variants (INSR-/-), and autoantibodies to the insulin receptor (Type B IR).
Patients with CGL and INSR +/- have less IR, lower glucose, higher BMI, and higher IGF-1 vs patients with INSR -/- and Type B INSR. Patients with INSR -/- have short stature, while those with CGL have tall stature. GH is comparable in all groups. After remission of Type B IR, patients had normalization of insulin resistance, glucose, and IGF-1, supporting the idea that IR or elevated glucose caused low IGF-1.
Our findings suggest that severe IR causes elevated blood glucose with inadequate glucose reaching cells mimicking a starvation state and causing low IGF-1. If this occurs during childhood growth (as in INSR -/-, but not in Type B IR), it leads to short stature.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN330 Patients with Recurrent Hypoglycemia Encounters Across Chicago: Who are they?
Authors: Zhao Lihui , Katz Joshua , Deng Yu , O’Brien Matthew , Furmanchuk A’lona , O’Connor Clare , Rosenman Marc , Kho Abel , Wallia Amisha 
Published: November 2022

Abstract
Hypoglycemia is an acute complication of diabetes management that has been linked to increased morbidity. Although current guidelines have called for treatment changes for avoidance of hypoglycemia, it remains a critical issue. Our goal was to examine the socio-demographic and clinical factors for recurrent hypoglycemic encounters across a large metropolitan area.
CAPriCORN is a research network which brings together merged, de-duplicated, and de-identified electronic medical health record data from 6 institutions across Chicago. Patients with a diabetes diagnosis and hypoglycemic encounters (HEs) between 2011-18 were identified using ICD-9 and 10 codes. HEs were identified using a validated algorithm. Analysis was performed to evaluate the patient characteristic differences between patients with 1 vs 2-3 vs ≥4 HEs utilizing chi-square for categorical variables and ANOVA for continuous variables.
Of 423,643 patients identified with a diagnosis of diabetes, 17,885 (4%) patients had at least one diagnosis of hypoglycemia, which included 30,157 unique encounters (1 HE: 12,886 pts and encounters; 2-3: 3,640 pts and 8,238 encounters, and ≥4: 1,359 pts and 9,033 encounters). The 1,359 patients with ≥4 HEs (8% of all patients with HEs) accounted for over 30% of all HEs.
Older adults (65 years and older) comprised 57% of all patients and 62% of patients with HEs. Older adults comprised 63% of those with 1 HE, 61% of those with 2-3, and 52% of those with ≥ 4 (p&lt; 0.001). Adults 80 years and older represented &gt; 20% of those in each group. Whites (N=7,203, 40%) and Blacks (N=6,511, 36%) accounted for most with HE, and within each category. Overall, among those with 1, 2-3, and ≥ 4 HEs there were also significant differences by race and ethnicity.
Patients with a HE had significant history of complications, including 54% with nephropathy, 24% with neuropathy, and 23% with ophthalmologic complications. However, a history of diabetic ketoacidosis (DKA) was noted in 53% of all patients with a HE, with 49%, 61%, and 66% of patients in 1, 2-3, and ≥4 HEs groups, respectively (p&lt;0.001).
Of those with medication information (n=8,938), patients on insulin-only therapy represented 47% of patients with a HE, and 44%, 52%, and 65% of patients who had 1, 2-3, and ≥4 HEs, respectively (p&lt;0.001). Patients on sulfonylureas or meglitinides represented 28% of patients with a HE, and 31%, 25%, and 15% of patients who had 1, 2-3, ≥4 HEs, respectively (p&lt;0.001). Of those with lab information for HbA1c (n=5,259) there was no significant difference between groups.
Overall, a small diverse group of patients accounted for a large amount of hypoglycemic encounters. Special attention should be paid to subsets of patients, including older adults, those with a history of DKA, and those on high-risk therapy.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF04 | PSUN135 Genetic Inactivation of Glutaminase Reduces Amino Acid Induced Alpha Cell Proliferation
Authors: Shou Matthew , Siv Walter , Debo Joshua , Sellick Katelyn , Reuter Austin , Stanley Jade E , Danielle Dean E 
Published: November 2022

Abstract
Glucagon stimulates glycogenolysis and gluconeogenesis in liver resulting in increased hepatic glucose output. Thus, interrupting glucagon signaling in liver reduces blood glucose levels in animal models and individuals with diabetes. However, interrupting glucagon signaling also leads to hyperaminoacidemia and proliferation of glucagon secreting alpha cells, evidence of an endocrine liver-alpha cell axis. Among the high amino acids, we previously identified high glutamine levels are required for alpha cell proliferation. We recently found that glutaminase (GLS) is expressed in alpha cells at much higher levels than any other pancreatic endocrine cells. Additionally, mouse pancreatic islets cultured in high amino acid containing media and treated with the small molecule inhibitor of GLS (CB839) have reduced alpha cell proliferation (Vehicle: 7.6 ± 2.2%, 0.1µM CB839: 0.11 ± 0.05%**, 10µM: 0.02 ± 0.01%**; n=3-4, **p &lt; 0.01). To further characterize the role of glutamine metabolism in glutamine-induced alpha cell proliferation, GLS activity was specifically knocked out in mouse alpha cells by breeding Gcg-CRE ERT2 with Glsflox mice (aGlsKO). Targeted deletion of Gls expression in most alpha cells was confirmed by staining for GLS and glucagon (aGlsWT: 95% GLS+, aGlsKO: 18% GLS+). Mice were treated with a glucagon receptor monoclonal antibody (GCGR mAb/mAb-4) for 10 days or with isotype control IgG. aGlsWT mice treated with GCGR mAb have robust alpha cell proliferation while aGlsKO mice treated with GCGR mAb for 10 days showed a 4.5-fold decrease in alpha cell proliferation and were similar to mice treated with the control IgG (aGlsWT Ab: 15.7 ± 3.6% alpha cell proliferation, aGlsWT IgG: 1.0 ± 0.4%***, aGlsKO Ab: 3.4 ± 0.6%**; n=4-6, ***p &lt; 0.001). In addition, aGlsWT mice treated with GCGR mAb showed a robust activation of mTOR in alpha cells as measured by phospho-S6 expression while this was lost in aGlsKO mice treated with GCGR mAb. Induced expression of the mTOR-dependent glutamine transporter SLC38A5 was also lost (aGlsWT Ab: 25.0 ± 4.8% alpha cell SLC38A5 expression, aGlsWT IgG: 0.40 ± 0.27%***, aGlsKO Ab: 3.7 ± 3.5%***, n= 2-4, ***p &lt; 0.001). Similar results on proliferation and mTOR activation in alpha cells were observed after 4 weeks of GCGR mAb treatment. Together these data suggest a critical role for glutamine metabolism via glutaminase in alpha cell proliferation.
Presentation: Saturday, June 11, 2022 1:36 p.m. - 1:41 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF16 | PSUN170 Prevalence of Fournier's Gangrene in T2DM Treated with Oral Antiglycemic Medications
Authors: Engel Ashley , Carroll Ty 
Published: November 2022

Abstract

Introduction
Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have become common pharmacotherapies in the treatment of type 2 diabetes mellitus. These agents are well described to increase the risk of genitourinary infections. Fournier's gangrene (FG), is a rare, life-threatening, necrotizing genitourinary infection with risk factors including diabetes, obesity, alcohol abuse, poor hygiene, immune suppression, malignancy, and HIV.1 An increased risk of FG has also been associated with the use of SGLT-2i; however, the exact risk of FG in association with SGLT-2i use is unknown.

Hypothesis
We hypothesized that SGLT-2i therapy did NOT increase the risk of FG when compared to other treatments for type 2 diabetes.

Methodology
We used the TriNetX database tool to search clinical data available within the Froedtert and the Medical College of Wisconsin system. The database was searched to identify patients with a diagnosis of type 2 diabetes and FG. From this data, we identified the number of patients with type 2 diabetes mellitus who developed FG based upon treatment with and without SGLT-2i exposure within 12 months. Patient characteristics including BMI, renal function, glycemic control, age, sex, tobacco use, and alcohol use were compared in both treatment arms.

Results
Data from 1.54 million patients showed that 143,330 (∼9.3%) carry a diagnosis of type 2 diabetes mellitus. Of these patients, 49,950 were treated with a SGLT-2i as part of their therapy while 44,510 patients were treated with oral antiglycemic agents without SGLT-2i exposure. Two hundred sixty of the 143,330 patients with diabetes (0.181%) developed FG. During a period of 12 months, 140 of 49,950 (0.280%) patients treated with a SGLT-2i developed FG. Whereas 120 of 44,510 (0.269%) without SGLT-2i therapy within a 12 month period developed FG. Patients’ characteristics (including sex, age, BMI, renal function, glycemic control, history of tobacco use, and alcohol use) were similar between the SGLT-2i therapy group and the group without SGLT-2i exposure.

Conclusion
We conclude patients treated with oral therapies for type 2 diabetes developed FG with similar frequencies regardless of exposure to SGLT-2i therapy. Patients with FG had similar characteristics and known risk factors regardless of SGLT-2i therapy utilization. Further study is required to determine if the previously noted association of FG and SGLT-2i treatment is due to the increased number of risk factors in the population receiving SGLT-2i therapy rather than the SGLT-2i themselves. References: 1. Bersoff-Matcha SJ, et al. Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases. Annals of Internal Medicine. 2019;170(11): 764-769.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m.
ODP439 Characteristics of Long COVID Symptoms and Utility of Serum Antibody Measurement for the Evaluation of Long COVID.
Authors: Sakurada Yasue , Sunada Naruhiko , Honda Hiroyuki , Tokumasu Kazuki , Otsuka Yuki , Hanayama Yoshihisa , Nakano Yasuhiro , Hasegawa Kou , Obika Mikako , Hagiya Hideharu , Otsuka Fumio 
Published: November 2022

Abstract
The pandemic of the new coronavirus infection (COVID-19) has yet not only to be converged, but also new infections continue to occur. At least about one-third of the affected patients suffer from various symptoms even after the acute phase. However, effective treatments for sequelae have not yet been established, and the prognosis and risk factors are still unclear. It is possible that endocrine disruption is involved in the occurrence of long COVID. Okayama University Hospital set up a COVID-19 aftercare (CAC) outpatient clinic on Feb. 15 in 2021 to treat patients suffering from sequelae even one month after COVID-19 infection. In the present study, to extract the key factors that affect the onset and course of sequelae, a retrospective analysis was performed by focusing on changes in the number of symptoms and patient background during the three months from the first outpatient visit. Also, we focused on how various sequelae progress in patients who received continuous medical care for 3 months, in which the relationship between the sequelae and the serum COVID-19 antibody titer measured at the first visit was evaluated. In this study, the data from 65 patients who visited our clinic.
Presentation: No date and time listed
ODP622 A Case of a Rare Steroid Cell Tumor in a Patient with PCOS
Authors: Elsheikh Sahar , Eduafo Augusta 
Published: November 2022

Abstract

Background
Ovarian sex cord-stromal tumors are rare and represent approximately 7% of all primary ovarian tumors. Steroid cell tumors of the ovary are uncommon sex-hormone secreting tumors and are classified as pure stromal tumors. These tumors are known to secrete hormones like androstenedione, alpha-hydroxyprogesterone, and testosterone. Polycystic Ovarian Syndrome (PCOS), a disorder affecting 6% to 10%, is characterized by hyperandrogenism and ovulatory dysfunction. We report a case of a patient with known PCOS who was found to have steroid secreting tumor.

Clinical Case
A 35 years old female presented to our office complaining of worsening hirsutism, amenorrhea and weight gain. Her past medical history was significant for PCOS, hypothyroidism, and obesity. Physical Examination was notable for hirsutism, obesity and clitoromegaly. Initial labs showed elevated testosterone level of 134 ng/dL (normal levels 0-70 ng/dL). Other labs ruled out congenital adrenal hyperplasia (CAH). Pelvic US was consistent with known PCOS but did not revealed additional findings. Endometrial biopsy was unremarkable. Subsequent labs showed continuous significant elevation in testosterone to 382 ng/dL with free testosterone level of 24 ng/dL. CT abdomen and pelvis with and without contrast showed a right solid adnexal mass. Patient underwent staging laparotomy with bilateral salpingo-oophorectomy. Pathology result was significant for well differentiated sex cord-stromal tumor, steroid secreting type. Genetic testing came positive for BRCA 1.

Conclusion
This case illustrates that in the setting of rapid onset of hirsutism and elevated testosterone, an androgen secreting ovarian tumor should be considered and ruled out, even in the setting of known PCOS.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON212 None-surgical sterilization of female dogs
Authors: Ko CheMyong J , Lin Po-Ching , Zhou Sherry , Hess Rex , Park Chanjin 
Published: November 2022

Abstract
Female pet dogs are sterilized by surgically removing their ovaries as a means to eliminate the source of germ cells and sex steroids. Surgical sterilization is inevitably invasive to the animals and costly to their owners, and an alternative method that is non-invasive and affordable has been long sought without success. In this study, a proof-of-concept of sterilizing female dogs by a non-surgical alternative was developed and successfully tested.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF22 | PMON03 Sex-specific Effects of Bisphenol-A and its Analogs on Monoamine Levels in the Paraventricular Nucleus
Authors: Mansi Maryam A , Chuang Yen-Jun , MohanKumar Puliyur , MohanKumar Sheba 
Published: November 2022

Abstract
Bisphenol A (BPA) is known to produce adverse effects on fertility, cardiovascular, and metabolic health. The constraints placed on BPA production led companies to switch to BPA's structural analogs, Bisphenol S (BPS) and Bisphenol F (BPF). These chemicals are used in various equipment, food and drink cans, and paper, permitting widespread exposure. We recently found that prenatal exposure to low levels of these chemicals can increase blood pressure in the offspring. However, the underlying neurobiological mechanism is unclear. We hypothesized that these chemicals could alter the levels of monoamines, specifically in brain regions that regulate cardiovascular function such as the paraventricular nucleus (PVN) of the hypothalamus. Pregnant Sprague Dawley rats were exposed to saline, 5 µg/kg BW of BPA or BPS, or 1 µg/kg BW of BPF from gestation day 6 to 21. Their adult Male and Female offspring were implanted with a radiotelemetry device to measure blood pressure and heart rate levels. Following telemetry, animals were sacrificed, and the brains were collected, frozen and sectioned. The PVN was microdissected, and analyzed for monoamine levels using HPLC-EC. Males exposed to BPA had significant increases in the levels of serotonin (5HT) in the PVN compared to the control group, while a marked increase in 5HT levels were only observed in females exposed to BPF and not BPA (p = 0.0002). No significant changes were observed in Dopamine (DA) or norepinephrine (NE) levels. There were significant sex differences (p&lt;0.0001) and treatment effects (p=0.0003) in the DOPAC/DA turnover ratio with males exposed to BPA, BPS, and BPF having markedly less turnover rates compared to control. No changes in DOPAC/DA turnover was apparent in females. There were significant sex (p&lt;0.0001) and treatment effects (p&lt;0.0001) in the 5HIAA/5HT turnover ratio, with males in the BPA and BPS groups having significantly less turnover compared to controls. In contrast, Females exposed to BPS and BPF had significantly lower 5HIAA/5HT turnover ratios but higher turnover ratios in the groups exposed to BPA. These results indicate that 5-HT production increases markedly in males exposed to BPA and in females exposed to BPF. This is associated with reduced metabolism of 5-HT. This suggests that the significant increases in 5-HT activity in the PVN could possibly contribute to the development of hypertension in these animals.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF22 | PMON06 The Contraceptive Synthetic-Progesterone Levonorgestrel (LNG) Significantly Accelerates Fetal Hypothalamic Neuronal Development (Neuroendogenesis) in the Zebrafish (Danio rerio).
Authors: Hinojosa Gabriella , Ruiz Mia , Garcia Kassandra , Dearth Robert 
Published: November 2022

Abstract
The fetal brain has a known vulnerability to exogenous influences due to its plasticity and high volume of replicating and differentiating cells. It is particularly susceptible to a group of environmental molecules classified as endocrine disrupting chemicals (EDCs). Previous vertebrate studies have provided supportive evidence that steroid mimicking EDCs might stimulate hypothalamic progenitor cell differentiation to neurons (neuroendogenesis). Changing the normal timing of neuroendogenesis could play a role in establishing an alternative developmental timeline leading to disruptions in key endocrine regulated process, like pubertal onset. Levonorgestrel (LNG), a synthetic progestin used in contraceptive pills, has been found at physiologically relevant levels in water sources worldwide. Therefore, we investigated the effect LNG had on neuroendogenesis in zebrafish (Danio rerio), an established comparative neurobiological animal model. Fertilized zebrafish embryos were collected (in-house breeding) and individually placed in 96-well plates. Starting at 3 hours post fertilization (hpf), embryos were exposed to either 5 ng of LNG (previously established physiologically relevant dose), 100ng of estradiol (E2, positive control) or a vehicle control for 5 days (5 dpf); covering the duration of neurogenesis. LNG had no effect on fertilization ratios, hatching or morphology compared to controls. On 5 dpf, larvae were paraffin-processed, slides were serially sectioned at (3-4 um) and prepped for immunohistochemistry (IHC). Brain tissue s were stained with hematoxylin and eosin (H&E) to identify regions of the brain including the hypothalamus and thalamus. Brain sections were also stained for the immunofluorescent (IF) neuronal marker α-HUC and/or estrogen receptor (ER) and imaged on a confocal microscope. The number of total cells, positive stained cells and negative stained cells were counted in the preoptic area (POA), rostral hypothalamus (RH) and thalamus, comparisons were made between groups. Interestingly, LNG significantly (p&lt;0.001) increased the number of positive cells expressing α-HUC in the hypothalamus compared to controls. Similar results were observed in the POA (p&lt; 0.01) and RH (p &lt;0.001) compared to their respective controls. Furthermore, we observed no significant changes in α-HUC expression in the thalamus due to LNG treatment comparted to controls. Our data suggests that LNG selectively targets hypothalamic neuronal development, accelerating neuroendogenesis increasing the number of endocrine-regulating neurons in the brain. This is the first study to show that exposure to low environmentally relevant levels of LNG increases neurons in the hypothalamus, thus, highlighting the possibility that LNG may target the brain to potentiate subsequent health issues later in life.
Presentation: No date and time listed