bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI024 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Female Mice
Authors: Young Demarrius 
Published: October 2023

Abstract
Disclosure: D. Young: None.
Introduction: Insulin resistance affects up to a third of the US adult population and polycystic ovary syndrome affects up to 10% of reproductive-age adult women. The liver and white adipose tissue play an essential component in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can increase predisposition to insulin resistance. Andrisse et al 2021 showed that deleting the liver androgen receptor (LivARKO) prevented female mice from developing hyperandrogenemia-induced insulin resistance. We wanted to know does LivARKO prevent high fructose diet (HFrD) induced insulin resistance? In our study, we placed female LivARKO mice on high fructose diets (HFrD) to determine if they demonstrated blunted insulin resistance. We hypothesized was that HFrD LivARKO female mice would display impaired insulin action in white adipose tissue. We needed to demonstrate that insulin signaling was functional in LivARKO mice on a control and a HFrD. There are six groups in this study: wild type (WT) no treatment, WT treatment-1, WT treatment-2, LivARKO no treatment, LivARKO treatment-1, and LivARKO treatment-2. No treatment is a chow diet, treatment-1 is a control diet, and treatment-2 is HFrD. Methods: Female LivARKO mice were placed on two diets: Control (Con, Research Diets Inc, RDI D12450J and High Fructose (HFrD, RDI D02022704. The mice were sacrificed after 1 month on the diet. Half of the mice were given a dose of 0.5 U/kg insulin before sacrificing to investigate the effects of the diets on insulin signaling. Western blots were used to determine protein expression in tissue from the white adipose tissue. BCA assays were used to standardize the protein concentration in each sample. Insulin action was measured molecularly by examining p-AKT Serine 473 ( Santa Cruz sc-514032) and p-IRS1 Serine 306 ( Santa Cruz sc-33956). If p-AKT S473 levels increase in the presence of insulin, indicating that insulin is likely functioning properly. If p-IRS1 S306 are elevated, indicates malfunctioning insulin or resistance. Results: LivARKO Female mice on a control diet did not express any insulin stimulated p-AKT in WAT, LivARKO Female mice on a high fructose diet displayed increased insulin stimulated p-AKT compared to LivARKO HFrD mice not given insulin. P-IRS1 was increased in the WAT of the Control Insulin group compared to the WAT of the Control Basal group of female LivARKO mice. Once placed on a HFrD, p-IRS1 was not present in the WAT either group of LivARKO mice. Conclusion: In conclusion, the data is inconclusive. HFrD appeared to augment insulin-stimulated p-AKT but lowered p-IRS1 in WAT of female LivARKO mice. There were several limitations to this study. We do not have data for LivARKO on chow or data for WT on control diet to decipher these effects. Further research is required into what components of the Control Diet are prompting this difference in insulin action.
Presentation: Friday, June 16, 2023
FRI037 Time-restricted Feeding Prevents Progression Of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Through IPMK
Authors: Jung Ik-Rak , Anokye-Danso Frederick , Jin Sunghee , Ahima Rexford S , Kim Sangwon 
Published: October 2023

Abstract
Disclosure: I. Jung: None. F. Anokye-Danso: None. S. Jin: None. R.S. Ahima: None. S. Kim: None.
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although many clinical trials for NAFLD treatment are undergoing, there are currently no approved therapies. Insulin resistance is central to the progression of NAFLD and implicated in disease progression from steatosis to NASH. Therefore, modulation of insulin resistance represents a potential strategy for NAFLD treatment. We have reported that inositol polyphosphate multikinase (IPMK), a key enzyme in inositol polyphosphate biosynthesis, plays a role in regulating hepatic insulin signaling and gluconeogenesis both in vitro and in vivo. However, the roles of IPMK in hepatic lipid metabolism were not investigated. To determine the role of IPMK in NAFLD/NASH, we fed high fat diet (HFD) or methionine-choline deficient diet (MCDD) in both wild type (WT) and liver-specific IPMK knockout (LKO) mice. We also examined the effect of time-restricted feeding (TRF), which is known to be beneficial for metabolic disease without influencing the food intake, in NAFDL/NASH. Here, we show that hepatic IPMK protein was decreased in WT mice fed a MCDD compared to a normal chow diet (ND) and loss of IPMK in the liver augments hepatic steatosis and steatohepatitis in mice fed a HFD as well as MCDD. Compared to the WT mice, triglycerides (TG) and pro-inflammatory gene expression in the liver increase significantly in the LKO mice fed HFD. Importantly, MCDD-fed LKO mice exhibit exacerbated NAFLD/NASH accompanied by an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic TG accumulation and fibrosis, and pro-inflammatory gene expression. Finally, TRF by limiting a food access only during the dark cycle led to an increase in expression hepatic IPMK protein in MCDD mice. Importantly, TRF alleviates NAFLD/NASH reflected by reduced hepatic TG accumulation, lowered serum ALT and AST levels, downregulated pro-inflammatory gene expression compared with ad libitum mice. Our results demonstrate that loss of IPMK mediates the progression of NAFLD/NASH and may be potentially targeted for treatment of NAFLD/NASH.
Presentation: Friday, June 16, 2023
FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls
Authors: Kaur Snimarjot , Singhal Vibha , Haidar Lea Abou , Bredella Miriam , Misra Madhusmita 
Published: October 2023

Abstract
Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None.
Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p&lt;0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites.
Presentation: Friday, June 16, 2023
FRI041 Obesity-associated Diaphragm Weakness Is Not Explained By Defects At The Level Of The Contractile Apparatus
Authors: Verma Romil Kaul , Claflin Dennis , Davis Carol , Converso-Baran Kimber , Michele Daniel , Brooks Susan , Chun Tae-Hwa , Buras Eric Dale 
Published: October 2023

Abstract
Disclosure: R. Kaul Verma: None. D. Claflin: None. C. Davis: None. K. Converso-Baran: None. D. Michele: None. S. Brooks: None. E.D. Buras: None.
Respiratory muscle dysfunction contributes to obesity-associated ventilatory disorders and is epidemiologically linked with diabetes and the metabolic syndrome. Despite its clinical relevance, the pathophysiology of obesity-related respiratory muscle weakness remains unclear. We previously applied non-invasive ultrasound to show that mice subjected to a 6-month diet-induced obesity (DIO) protocol develop diaphragm motion abnormalities. Isometric contractile force—measured ex vivo on isolated diaphragm strips—also declines with 6-month high fat diet (HFD) feeding, demonstrating that overnutrition causes functional impairment intrinsic to the diaphragm muscle. Intra-diaphragmatic adipocyte number and polymerized collagen content both increase with long-term DIO; however, their occupation of muscle cross sectional area (CSA) is insufficient to quantitatively account for force generation deficits. While disruption of tissue architecture secondary to intramuscular adiposity and fibrosis might underlie diaphragm contractile dysfunction, it is also possible that obesity impairs force production in individual myofibers. The functional integrity of the contractile apparatus (ie the sarcomere) can be interrogated in single myofibers. In this approach, muscle samples are subjected to membrane permeabilization, then individual myofibers are mechanically dissected out and affixed to a force transducer apparatus in which isometric contraction is stimulated via calcium administration. An attached camera allows for measurement of fiber CSA, such that specific force (measured force per unit CSA) can be calculated. We measured isometric specific force on both diaphragm strips and permeabilized single myofiber segments isolated from mice fed control diet (CD) or HFD feeding for periods of 6 weeks or 6 months. At the 6-week time point, muscle strip specific force was indistinguishable between groups; however, at 6 months, this parameter was significantly lower in samples from HFD-fed mice—consistent with our previous findings. In contrast, specific force measurements taken from individual myofibers were equivalent between CD and HFD-fed mice at both 6-week and 6-month time points. These data demonstrate that long-term DIO is required to reduce diaphragm contractile force; and that this decline occurs at the level of the tissue rather than the single myofiber contractile apparatus.
Presentation: Friday, June 16, 2023
FRI052 Z-score Of The Log-transformed A Body Shape Index As A Screening Tool For Sarcopenia In Population With Central Obesity
Authors: Chung Hye Soo 
Published: October 2023

Abstract
Disclosure: H. Chung: None.
Background: Sarcopenic obesity is related with a higher risk of cardiovascular disease, metabolic disease, and mortality than obesity alone. Nevertheless, few studies have investigated body shape indices for the assessment of sarcopenia in obese populations. The purpose of this study was to evaluate the accuracy of the Z-score of the log-transformed A Body Shape Index (LBSIZ) to assess sarcopenia in nationally representative populations with central obesity. Methods: Data from Korea NHANES (KNHANES) and the U.S. National Health and Nutrition Examination Survey (U.S. NHANES) were evaluated. Sarcopenia for the Korean population it was defined when appendicular skeletal mass index (ASMI ) &lt; 7 kg/m2 in men or ASMI &lt; 5.4 kg/m2 in women, according to the Asian Working Group for Sarcopenia and for the American population was defined when ASMI &lt; 7 kg/m2 in men or ASMI &lt; 5.5 kg/m2 in women, according to the revised European consensus on definition and diagnosis for sarcopenia. LBSIZ cut-off value was defined as that with the highest score of the Youden’s index. Changes in odds ratios (OR) for sarcopenia were investigated using restricted cubic spline (RCS) plots. Results: This study was conducted for population with central obesity in 4,855 Koreans and 8,010 Americans. Among these, 330 Koreans and 373 Americans were accompanied with sarcopenia. The cut-off values for the LBSIZ were 1.15 (sensitivity, 78%; specificity, 77%) for Korean men, 0.95 (sensitivity, 74%; specificity, 69%) for Korean women, 1.05 (sensitivity, 88%; specificity, 82%) for American men, and 0.45 (sensitivity, 77%; specificity, 71%) for American women in the development groups. Comparable results were verified in validation groups. The RCS plot indicated that ORs for sarcopenia rapidly increased with an increase in the LBSIZ cut-off value. Conclusion: The LBSIZ index is a powerful and reliable indicator of sarcopenia in adults with central obesity.
Presentation: Friday, June 16, 2023
SAT135 Prospective Analysis For Improvement For Glycemic Control Using A Patient Portal And Automated Messages
Authors: Cristancho Cagney C , Brandao Marjorie , Morocho Alexandra Lema , Amorim Talmas 
Published: October 2023

Abstract
Disclosure: C.C. Cristancho: None. M. Brandao: None. A. Lema Morocho: None. T. Amorim: None.
Background: Type II diabetes is a complex metabolic disorder which is influenced in part by patient dietary choices, medication adherence, and environmental factors. Behavioral health interventions offer an opportunity to potentially affect patient outcomes in a cost-effective manner. Purpose: To study whether automated clinical messaging via the electronic medical chart would be associated with improvement in diabetes-related health measures. Methods: We created an automated clinical messaging system (January 2020) via our electronic medical record. Patients who opted-in for this service received bi-weekly messages which included reminders about diabetes medication adherence as well as exercise and dietary recommendations. We then performed a retrospective longitudinal analysis of patients followed in our diabetes clinic, comparing those who opted-in for messing vs those who did not, and assessed diabetes-related biomarkers including baseline and follow-up hemoglobin A1c, lipid markers, and BMI using linear mixed-effects regression models. Results: 69 patients who had at least 2 measures of hemoglobin A1c were followed longitudinally, of whom 37 (54%) had opted to receive automated messaging. Patients who opted-in were younger (53±12 vs 62±11 years old, p&lt;0.1), but not different in terms of sex (60% F vs 61% F), BMI (31±6 vs 30±7, p=0.84), or A1c (9.4±2.3 vs 8.8±2.7, p=0.34). In the group that received messages, we did not find any significant pre-post differences in A1c, LDL, or BMI over time. In the opt-in group, mean change (over average follow-up of 256 days) in HgbA1c was -0.4 (p=0.42) compared to a change of 0.0 in the non-opt-in group (p=0.99). Discussion: Patients who opted-in to electronic messaging were younger on average. We did not observe any significant longitudinal change in diabetes-related biomarkers within or between groups as related to an automated clinical messaging service, although there was a directional trend toward improvement. Given the cost-effectiveness and ease of this program, consideration should be given toward a trial with a larger sample size and longer follow-up.
Presentation: Saturday, June 17, 2023
SAT155 Insulin Receptor Autoantibody Syndrome (Iras): A Rare Occurrence In Lymphoproliferative Disease
Authors: Santos Claudia Villatoro , Oral Elif A 
Published: October 2023

Abstract
Disclosure: C. Villatoro Santos: None. E.A. Oral: None.
Insulin receptor antibody syndrome (IRAS) may present as fasting hypoglycemia, high serum insulin, and serum autoantibodies to insulin receptor at low titers. We present a case of a patient with multiple myeloma (MM) who developed hypoglycemia suspected to be related to insulin receptor antibodies. The patient is a 60-year-old male with history of prediabetes, MM, anemia, and thrombocytopenia treated with carfilzomib, dexamethasone 20 mg weekly, and prior radiation to the right pelvis, who presented to the hospital for increased right hip pain and cough. Patient reported 4 days of markedly decreased appetite with poor intake. He noted increased chronic right hip and low back pain. On exam, he was cachectic, had hyperpigmentation under bilateral eyes, and muscle wasting. Hypoglycemia as low as 38 mg/dL (70-180 mg/dL) was noted. MM studies on hospital day 4 showed increased kappa-M protein and kappa-free light chains with worsening anemia and thrombocytopenia, concerning for progression of his disease. He later developed recurrent hypoglycemia; endocrinology was consulted on hospital day 6. He also had hyponatremia and borderline low blood pressure. Cortisol on hospital day 7 at 9:00 am was 15.4 μg/dL (5.3-22.5 μg/dL) in the setting of normoglycemia. On hospital day 9, hematology started dexamethasone 40 mg daily for 3 days for MM relapse, which resulted in marked improvement in his mental status, appetite, and resolution of hypoglycemia. On hospital day 11, he started weekly cyclophosphamide, bortezomib, plus dexamethasone for 3 weeks. Results for hypoglycemia workup returned on hospital day 12 from samples of Day 7: glucose 53 mg/dL (70-180 mg/dL), C-peptide 0.2 ng/mL (1-5.2 ng/mL), insulin 14.6 μU/mL (1-21 μU/mL), insulin antibodies undetectable, negative serum screen for oral hypoglycemic agents. His course was complicated by sepsis with gram-negative bacteremia treated with antibiotics and stress dose hydrocortisone. He was discharged to rehab on hospital day 34 on dexamethasone 4 mg daily. Glucose, c-peptide and insulin levels could be consistent with exogenous hyperinsulinemic hypoglycemia but may also represent delayed insulin clearance due to insulin receptor antibodies and autocrine suppression of pancreatic insulin production in a patient with no access to insulin. Therefore, the most likely diagnosis was IRAS. The insulin antibody radioactive essay was negative for native IgG and IgM antibodies; testing for insulin receptor antibodies is in progress as a clinical test is unavailable. Treatment is common with high doses of steroids. IRAs can be seen in patients with lymphoproliferative disorders and would respond to steroid treatment for hospital management. Definitive treatment should be tailored with oncology guidance. There is a need for an accessible clinical test for IRAS in the US.
Presentation: Saturday, June 17, 2023
THU017 Severe Hypercortisolemia- A Biological Time Bomb
Authors: Munasinghe Uthpala , Pittampalli Shanti , Das Dhriti , Pattan Vishwanath 
Published: October 2023

Abstract
Disclosure: U. Munasinghe: None. S. Pittampalli: None. D. Das: None. V. Pattan: None.
Cushing's disease, the most common cause of endogenous Cushing syndrome, is usually insidious and has less severe hypercortisolemia than ectopic Cushing's. 73 yr.old female with hypertension, hyperlipidemia, T2DM, and OSA on anticoagulation for recent pulmonary embolism, presented with recurrent hypokalemia and proximal muscle weakness of 3 months duration. She denied visual symptoms and headaches. BP was 158/90 mmHg, HR 92 bpm, and BMI 34.9. She had a round face with ruddy complexion, extensive bruising on her upper extremities and proximal muscle weakness. Laboratory tests showed serum bicarbonate 26 mmol/l (22-29), sodium 140 mmol/L (136-145), potassium 2.0 mom/L (3.4- 5.1), chloride 106 mmol/L (98-107), glucose 164 mg/dl. Hemoglobin A1c 9.6 %, random cortisol 46.2mcg/dL, ACTH 72.4 pg/ml (7.2-63.3), late-night salivary cortisol sample was inadequate to assess, 24-hour urine cortisol 1802 ug/24 hr (6-42). Prolactin level was 14.6 ng/ml(4.7-23.3), IGF-1 62 ng/dl (48-191), GH 0.12 ng/ml (0-3.61), FSH&lt; 0.3 mU/ml (25.8-134.8), TSH 0.193 u/ml (0.27-4.2), Ft4 1.1 ng/dl (0.93-1.7), alpha subunit &lt;0.15 ng/ml (&lt;3.56). She had non-suppressed cortisol of 44.3 mcg/dL and ACTH of 113 pg/mL after overnight 8mg dexamethasone suppression test. CT angiogram chest did not reveal any pathology. MRI pituitary revealed pituitary adenoma measuring 9 x 8 mm. IPSS with desmopressin stimulation showed IPSS to peripheral prolactin ratio was greater than 1.8 verifying successful catheterization. Her central to peripheral ACTH gradient was &gt;2 before stimulation confirming pituitary source. Her ACTH concentration gradient &gt;1.4 between 2 sinuses lateralizing the lesion to the right. The patient was started on Osilodrostat 2mg bid for control of hypercortisolemia and subsequently treated with transsphenoidal resection of the pituitary adenoma. Surgical pathology was consistent with densely granulated corticotrophin adenoma. Initial presentation of recurrent hypokalemia, proximal muscle weakness, pulmonary embolism and severe hypercortisolemia was suspicious for ectopic Cushing’s but after initial chest imaging was negative for ectopic pathology, MRI and subsequent IPSS helped with timely diagnoses and management. Severe hypercortisolemia is an endocrine emergency carrying high mortality. Expedited diagnoses, control of hypercortisolemia, anticoagulation and antibiotic prophylaxis can be life saving before definitive treatment can be done.
Presentation: Thursday, June 15, 2023