bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI141 Dietary Salt Regulates mTORC1 Signaling In Humans And Mice With Hypertension
Authors: Aljaibeji Hayat , Brooks Daniele L , Garza Amanda E , Gerges Peter , Heydarpour Mahyar , Luminita Pojoga , Williams Jonathan S , Williams Gordon , Romero Jose R 
Published: October 2023

Abstract
Disclosure: H. Aljaibeji: None. D.L. Brooks: None. A.E. Garza: None. P. Gerges: None. M. Heydarpour: None. P. Luminita: None. J.S. Williams: None. G. Williams: None. J.R. Romero: None.
Raptor and the mammalian target of rapamycin (mTOR) form a complex (mTORC1) that has been proposed to play a role in aldosterone (ALDO) production. Pharmacological inhibition of mTORC1 reduces blood pressure (BP) and ALDO levels. However, the effects of environmental factors such as dietary salt on mTORC1 in humans are unclear. We studied the impact of one-week liberal Na+ (LIB, 200 mmol/day) and restricted (RES, 10 mmol/day) Na+ diets on Raptor and mTOR expression in human peripheral blood mononuclear cells (PBMC) from hypertensive subjects. Raptor and mTOR expression were higher on PBMCs from subjects on a LIB than on RES Na+ diet (n=13; P=0.036 and P=0.0008, respectively). We also studied Caucasian subjects (n=792) from the Hypertensive Pathotype (HyperPATH) cohort using the Multi-Ethnic Genotyping Array on the Illumina platform. Candidate gene association analyses showed that the single nucleotide polymorphic (SNP) Raptor gene variant, rs99001846, was associated with BP and ALDO levels. Multivariate linear regression analyses performed on hypertensive and normotensive participants showed that in hypertensives, rs99001846 risk allele carriers (AA/GA), as compared to non-risk carriers (GG), were associated with increased systolic BP levels on bothLIB and RES Na+ diets (P=0.02, P=0.01 respectively). In addition, risk allele carriers, as compared to non-risk carriers, showed increased ALDO and reduced Na+ excretion on a LIB Na+ diet (P=0.009, P=0.025, respectively). We also studied a mouse model of low nitric oxide and high AngII-mediated hypertension and observed increased cardiac Raptor and mTOR expression (n=4, P=0.0008 and P=0.03 respectively). We then performed in silico bioinformatic analyses of rat zona glomerulosa cells following 2 hr treatment with 100 nM angiotensin II (AngII) using the Gene Expression Omnibus (GEO). AngII treatment led to the activation of mTOR signaling pathways as shown by increased expression of insulin receptor substrate type 2 (P=0.00001) and Low-density lipoprotein-related receptor 5 (P=0.03). Also, AngII reduced the expression of Eukaryotic Translation Initiation Factor 4E Binding Protein 1 by 43% (P= 0.001) and increased expression of CAP-Gly Domain Containing Linker Protein 1 by 70% (P= 0.00003) - important signaling molecules that are downstream of mTOR activation. Our results suggest that in hypertension, Na+ intake and Raptor gene variants modify mTORC1. Thus, mTOR/Raptor expression are a potential biomarker of ALDO-mediated cardiovascular injury.
Presentation: Friday, June 16, 2023
FRI142 The Pathophysiologic Spectrum Of Primary Aldosteronism Determined Via Saline Suppression Testing In Overweight Hypertensive And Pre-hypertensive People
Authors: Warachit Parksook Wasita , Michelle Brown Jenifer , Milks Julia , Moore Anna , Niebuhr Yvonne , Honzel Brooke , Vaidya Anand 
Published: October 2023

Abstract
Disclosure: W.W. Parksook: None. J.M. Brown: Consulting Fee; Self; Bayer, Inc. J. Milks: None. A. Moore: None. Y. Niebuhr: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept, HRA Pharmaceuticals, Mineralys.
Background: Emerging evidence shows that primary aldosteronism is not a categorical condition, but rather a pathophysiologic continuum that manifests across a broad range of severity. Saline suppression testing has long been used to “confirm” primary aldosteronism while employing relatively arbitrary and categorical thresholds. Methods: Overweight to obese participants with metabolic risk factors and pre-hypertension or stage 1 hypertension with suppressed renin activity (&lt;1.0 ng/mL/h) (n=42) underwent deep phenotyping protocols to assess the pathophysiologic continuum of the primary aldosteronism phenotype. Participants completed a seated saline suppression test (SSST), to maximally suppress Angiotensin II-mediated aldosterone production, and dexamethasone suppression and cosyntropin stimulation testing, to maximally suppress and stimulate ACTH-mediated aldosterone production. The association of each parameter with the continuum of aldosterone levels was assessed using linear regression. Results: Following SSST, there was a continuum of non-suppressible and renin-independent aldosterone production. Categorically, 29% of participants had post-SSST plasma aldosterone levels ≥10 ng/dL, and another 45% had levels 6-10 ng/dL; however, there was a continuous spectrum of aldosterone values above and below these arbitrary thresholds. Across the continuum of post-SSST aldosterone levels, greater non-suppressibility of aldosterone was associated with greater non-suppressibility of aldosterone post-dexamethasone (β= 1.05, P&lt;0.001), greater stimulation of aldosterone post-cosyntropin administration (β= 1.42, P&lt;0.001), and greater aldosterone-to-renin ratio (β= 3.44, P=0.01). Conclusion: Despite existing categorical thresholds for SSST, dynamic phenotyping studies in overweight/obese stage I hypertensive and pre-hypertensive individuals demonstrate a continuum of non-suppressible and renin-independent aldosterone production following SSST that parallels higher levels of ACTH-dependent aldosterone production. These findings underscore the fallibility of currently recommended diagnostic limits for SSST and suggest that primary aldosteronism pathophysiology transcends these relatively arbitrary thresholds.
Presentation: Friday, June 16, 2023
OR24-06 The Role Of Oxidative Stress In The Association Of Smoking And Alcohol Consumption With Hepatic Steatosis
Authors: Shaheen Magda , Schrode Katrina , Pan Deyu , Michael Najjar Sonia , Friedman Theodore C 
Published: October 2023

Abstract
Disclosure: M. Shaheen: None. K. Schrode: None. D. Pan: None. S.M. Najjar: None. T.C. Friedman: None.
Hepatic steatosis (HS) is the most prevalent chronic liver disease in the United States. While heavy alcohol consumption is known to be a risk factor for HS, the effect of moderate consumption is still debated. Similarly, while smoking is a known risk factor for many chronic conditions, its contribution to HS is still in question. A potential mechanism by which these factors could increase risk for HS is through oxidative stress. Oxidative stress is an imbalance between free radicals and antioxidants in the body that causes inflammation and cellular damage. Behaviors such as smoking and alcohol consumption are thought to increase oxidative stress. This study aims to determine the role of oxidative stress in the relationship between smoking and moderate alcohol consumption with HS among the adult population of the United States. We analyzed data for 3444 participants from the National Health and Nutrition Examination Survey 2017-2018. Hepatic steatosis was measured by FibroScan® using controlled attenuation parameter (CAP) values, and we used levels of γ-glutamyltransferase (GGT) as a biomarker for oxidative stress. We categorized alcohol consumption and smoking as none, former (for smoking), light, and moderate-heavy following the National Center for Health Statistics. We used bivariate chi square analysis and multivariable logistic regression adjusting for the demographics, laboratory, and co-morbidity and consider the design and weight. We developed two models with and without oxidative stress. In bivariate analyses, oxidative stress was significantly associated with heavier smoking and alcohol consumption, and with HS (all p&lt;0.05). A multivariable model without oxidative stress showed that light drinking alone, light smoking alone, and combination of light smoking and light drinking were not associated with HS (p&gt;0.05), but moderate-heavy smoking combined with light drinking or moderate-heavy drinking increased the odds of HS compared to abstinence from both smoking and drinking (Adjusted Odds Ratio [AOR]=3.9, 95% Confidence Interval [95% CI]= 1.5 - 10.2, p=0.006; AOR=6.2, 95% CI= 1.4 - 26.9, p= 0.014, respectively). When we included oxidative stress in the model, oxidative stress was independently associated with HS (AOR=1.1, 95% Ci=1.0-1.1, p=0.011) and the odds ratios for the interaction of smoking and alcohol did not change, indicating that oxidative stress was not a mediator of these relationships. Our findings indicated that smoking and alcohol consumption can interact to increase the odds of HS in the US population independent of oxidative stress. Further research is needed to identify the underlying mechanisms.Grants: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881
Presentation: Saturday, June 17, 2023
THU244 Clinical Factors Affecting Dapagliflozin Response For Glycemic Control And Body Weight Reduction: Post-hoc Analysis Of BEYOND Study
Authors: Jeung Ahn Kyu , Ji Eun Jun , In-Kyung Jeong 
Published: October 2023

Abstract
Disclosure: K. Ahn: None. J. Ji Eun: None. J. In-Kyung: None.
Background: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, ameliorates hyperglycemia and obesity by inhibiting renal glucose reabsorption. However, significant heterogeneity exists in glucose-lowering efficacy and the magnitude of the weight loss among patients with type 2 diabetes. Herein, we aimed to evaluate the clinical factors affecting response to dapagliflozin treatment. Methods: We performed a post-hoc analysis of the BEYOND (Effects of Dapagliflozin Compared with Glimepiride on Body Composition in Patients with Type 2 Diabetes Inadequately Controlled with Metformin) randomized, double-blind, parallel-group trial. Patients were randomly assigned (1:1) to receive the addition of either dapagliflozin 10 mg per day or glimepiride 1∼2 mg per day to background metformin therapy for 52 weeks. Changes in HbA1c and body weight from baseline during the observation period were assessed for all patients. Responder to dapagliflozin was defined by &gt;1% reduction in A1c and &gt;3% reduction in body weight at week 52. Then, we classified the total subjects into 4 groups: non-responder of both A1c reduction and body weight reduction, responders of A1c reduction but non-responder of body weight reduction, non-responder of A1c reduction but responders of body weight reduction, and responders of both A1c reduction and body weight reduction.
Results: Among 56 patients in a dapagliflozin arm, 55.4% (N = 31) and 57.1% (N = 32) experienced clinical responses as indicated by reductions in HbA1c and in body weight reduction, respectively. Younger age and higher HbA1c level at baseline were significantly associated with a greater HbA1c reduction, and a higher estimated glomerular filtration rate (eGFR) was significantly associated with a greater body weight reduction. However, there was no association between the change in HbA1c and the change in body weight (r = −0.133, P = 0.328). Responders of both A1c reduction and body weight reduction were most common (32.1%), non-responders of A1c reduction but responders of body weight reduction were second-most (25.0%), responders of A1c reduction but non-responders of body weight reduction were 23.2%, and non-responders of both A1c reduction and body weight reduction were 19.6%. Subjects with higher fasting plasma glucose (FPG) and HbA1c in addition to lower eGFR at baseline had a greater reduction in HbA1c, but less reduction in body weight. Conversely, those with lower FPG and HbA1c in addition to higher eGFR at baseline had a greater reduction in body weight, but less reduction in HbA1c level. Conclusion: Patients with type 2 diabetes actually exhibit a heterogeneous response to dapagliflozin treatment. Glucose-lowering efficacy of dapagliflozin was associated with worse baseline glycemic status, and body weight reduction was associated with baseline higher eGFR.
Presentation: Thursday, June 15, 2023
THU278 Hidden In The Immune System: Exogenous Insulin Antibody Syndrome In A Patient With Latent Autoimmune Diabetes In Adults
Authors: King Hannah L , Nagappan Raj , Sliwinska Aleksandra 
Published: October 2023

Abstract
Disclosure: H.L. King: None. R. Nagappan: None. A. Sliwinska: None.
Hidden in the Immune System: Exogenous Insulin Antibody Syndrome in a Patient with Latent Autoimmune Diabetes in Adults
Background: Exogenous insulin antibody syndrome (EIAS) is a rare syndrome associated with insulin antibodies induced by exogenous insulin, found predominantly in patients with type 2 diabetes using various insulin formulations. Here, we present a case of young man previously diagnosed with type 2 diabetes, who was found to have severe refractory diabetic ketoacidosis (DKA) due to EIAS. Clinical Case: A 46-year-old man with a history of type 2 diabetes presented to an outside hospital for one week of fever and malaise. Laboratory studies were notable for serum glucose of 600 mg/dL (70-90mg/dL), HCO3 3 mmol/L (22-28mmol/L), and creatinine of 3.9 mg/dL (0.7-1.3mg/dL). He was diagnosed with DKA, shock and renal failure. During hospital stay, he remained on an insulin drip due to multiple unsuccessful attempts of transitioning to subcutaneous insulin, requiring over 1000 Units of insulin daily. This prompted insulin antibody testing that resulted elevated at &gt;50U/mL (0-0.4U/mL), concerning for EIAS. Treatment was initiated with 5 days of IVIG and mycophenolate mofetil. During this treatment, his baseline insulin infusion rate of 30 Units/hr declined to 18 Units/hr, however at day 3, insulin requirements again increased. For better evaluation, quantitative insulin antibody values were requested and resulted as 362.5U/mL, followed by 350.9U/mL post IVIG treatment. After no significant improvement, patient was transferred to our hospital for further management of EIAS. Plasmapheresis was initiated followed by rituximab with plans for long term maintenance therapy. Dexamethasone was trialed but shortly after discontinued due concern of increased insulin resistance and hyperglycemia. Metformin was also started but discontinued due to concern of worsening acidosis in the setting of acute renal failure requiring CRRT. Ultimately, the patient was transitioned to subcutaneous U500 BID 75-150 Units based on scale. At discharge, metformin and pioglitazone were started. Due to the history of early onset insulin-dependent diabetes at age 30, he was tested for GAD-65 which resulted as positive at 0.28 nmol/L (&lt;=0.02 nmol/L) and C peptide of 0.9ng/mL (0.8 - 3.9 ng/mL) consistent with LADA. Conclusion: EIAS is a rare and very challenging entity, increasing risks of severe ketoacidosis, hypoglycemic episodes and numerous other complications. Although mostly reported in type 2 diabetes, EIAS can occur in patients with LADA suggesting that autoimmunity may play a role. There is no FDA approved treatment, however attempts focus on eliminating antibodies by plasmapheresis, IVIG and immunotherapeutic agents.
Presentation: Thursday, June 15, 2023
THU280 Acute Interstitial Nephritis- A Complication Of Semaglutide Use
Authors: Alsayed Hasan Marah , Doroshow Jonathan 
Published: October 2023

Abstract
Disclosure: M. Alsayed Hasan: None. J. Doroshow: None.
Background: With the widespread use of glucagon-like peptide 1 (GLP-1) agonists in diabetes, several cases have been reported of GLP-1 induced acute interstitial nephritis (AIN) with variable recovery in kidney function (1). Although it is a rare side effect, the primary management requires early identification and removal of the offending agent. Clinical Case: A 75-year-old male presented with a week of nausea, vomiting, abdominal pain, and reduced urine output. He was started on semaglutide 4 months prior to admission when his creatinine was 1.16 mg/dL. Initial lab abnormalities included an elevated blood urea nitrogen 119 mg/dL (n 8-20 mg/dL), elevated creatinine 13.8 mg/dL (n 0.7-1.3 mg/dL), anion gap acidosis with a CO2 of 15 mEq/L (n 22-32 mEq/L) and an anion gap of 18 (n&lt;12), lipase 659 U/L (n 20-51 U/L). His urinalysis demonstrated too numerous to count red blood cells, 4-10 white blood cells, rare eosinophils and no casts or crystals. Urine culture was negative. The fractional excretion of sodium and urea were 5.56% and 56% respectively, consistent with intrinsic renal disease. CT of the abdomen and pelvis demonstrated peri-pancreatic inflammation. A follow up renal ultrasound showed normal echotexture with no hydronephrosis or renal calculi. His picture was concerning for pancreatitis and pre-renal/acute tubular necrosis from diuretic use and vomiting. Despite aggressive fluid resuscitation, there was minimal improvement in his creatinine. Further work up for his renal injury was negative for monoclonal antibodies on protein electrophoresis and immunofixation. An autoimmune work up was negative for antinuclear antibody, anti-double stranded DNA, antineutrophil cytoplasmic (ANCA) myeloperoxidase IgG, anti-proteinase 3 ANCA IgG, glomerular basement membrane antibody, hepatitis B and C antibodies, and HIV. Complements and immunoglobin G subclasses were normal. A renal biopsy was performed which showed active interstitial inflammation with eosinophils consistent with allergic interstitial nephritis without an immune complex mediated glomerular lesion. He was started on intravenous methyl prednisone for 3 days followed by a prednisone taper. His home metformin, ramipril and hydrochlorothiazide were discontinued on discharge. He was eventually started on mycophenolate as the creatinine did not return to baseline with steroids. Conclusion: AIN is a rare, yet serious complication of GLP-1 use that requires early identification and discontinuation of the medication. A rapid or unexplained decline in renal function after starting a GLP-1 should be evaluated early on with concern for AIN once volume depletion is ruled out (1).
Reference: (1) Chaudhury N., Liarakos A., Gopalakrishnan K., Ayub W., Murthy N., Rao R. Antidiabetic medication-induced acute interstitial nephritis: case report and literature search. British Journal of Diabetes. 2021;21(2);228-32.
Presentation: Thursday, June 15, 2023
THU312 The Type 1 Diabetes Susceptible LEW.1WR1 Rat Develops Insulin Resistance And Severe Non-alcoholic Fatty Liver Disease
Authors: Tahirah Love-Rutledge Sharifa , Wimalarathne Madushika , Mercado Luis D , Smiley Alan , Riley Apperson Christopher , Wilkerson Vidal Quiana C 
Published: October 2023

Abstract
Disclosure: S.T. Love-Rutledge: None. M. Wimalarathne: None. L.D. Mercado: None. A. Smiley: None. C. Apperson: None. Q.C. Vidal: None.
A subpopulation of type 1 diabetes patients develop the pathophysiological parameters to be termed double diabetes. This patient population often develops obesity, non-alcoholic fatty liver disease, and other hallmarks of insulin resistance. The LEW.1WR1 rat is a type 1 diabetes susceptible rodent with hyperinsulinemia that has shown signs of fatty liver infiltration1,2. We hypothesized that LEW.1WR1 rats would develop insulin resistance and severe nonalcoholic fatty liver disease due to its increased circulating insulin and predisposition to autoimmune disease. LEW.1WR1 rats and Wistar Furth rats were used for the 18-week long experiment. Peripheral insulin sensitivity was evaluated using insulin tolerance tests at weeks 11 and 17 showing worsening insulin sensitivity as evidenced by the gradual slope compared to the steep slope of the Wistar Furth rats. HOMA-IR values support LEW.1WR1 rats develop worsening insulin sensitivity and are insulin resistant at week 23 of the experiment (2.613± 0.796, p &lt; 0.0001). Terminal liver mass confirmed increased liver mass normalized to body mass and liver triglyceride levels suggested increased ectopic lid accumulation in the liver (Liver Mass 2.65% ±0.32 p = 0.0005 and triglyceride levels 192.8 ± 21.85 mg/dL, p = 0.034). The H&E-stained digital liver slides were scored for liver ballooning, steatosis, and markers of inflammation. Fibrosis and terminal circulating cytokines were also measured to assess severity of condition. While both groups showed increased steatosis and injury ballooning, trichrome blue staining and inflammatory cytokines verify the severity of disease in the LEW.1WR1 rats. LEW rats have increased fibrosis area and high serum TNF-α, IFN-, MCP-1 levels. As hypothesized, we observed that LEW.1WR1 rats show characteristics of insulin resistance and malignant nonalcoholic fatty liver disease development.
References: (1) Wilkerson-Vidal, et al. Mol. Cell. Endocrinol. 2023; 562:111837. (2) Mordes et al, Diabetes. 2005;54(9):2727-2733.
Presentation: Thursday, June 15, 2023
THU342 Per And Polyfluoroalkyl Substances And Prevalence Of Diabetes Mellitus In Korean Adults
Authors: Kim Shin-Hye 
Published: October 2023

Abstract
Disclosure: S. Kim: None.
Objectives: Recent epidemiologic research has studied the relationship between Per- and polyfluoroalkyl substances (PFAS) and diabetes mellitus (DM), yet the findings have been inconsistent. We examined the association between serum PFAS concentrations and the prevalence of diabetes in the Korean general population. Methods: We analyzed the data of 2,993 participants aged ≥ aged 19 years who participated in the Korean National Environmental Health Survey (KoNEHS) Cycle 4 (2018-2020). Serum concentrations of 5 PFAS [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS)] were quantified using using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Individuals with DM were identified by the presence of one or more of the following conditions: (1) self-reported diabetes; (2) use of a glucose-lowering medication; (3) hemoglobin A1c ≥6.5%. Multiple logistic regression models were used to examine the associations between PFAS concentrations and DM after adjusting for age, sex, central obesity, education levels, smoking status, alcohol consumption, physical activity, and frequency of delivery food consumption. Bayesian kernel machine regression (BKMR) was used to investigate the independent and combined relationship between PFAS exposure and DM prevalence. Results: The prevalence of DM was 11.8%. The odds ratios (95% confidence intervals) of DM in the highest quartile relative to the lowest were 0.85 (0.56, 1.32) for PFOA, 1.39 (0.87, 2.23) for PFNA, 0.95 (0.63, 1.43) for PFDeA, 1.52 (1.01, 2.35) for PFHsS, 1.26 (0.77, 2.05) for PFOS and 1.01 (0.66, 1.55) for the sum of PFAS. According to the BKMR model results, PFNA and PFHxS were positively associated with an increased risk of DM, while PFOA and PFDeA were negatively associated. The risk of DM appeared to rise in correlation with the PFAS mixture quartile, but the association was statistically insignificant. Conclusions: Different associations between PFAS concentrations and DM were observed according to the PFAS isomers. Further studies are needed to clarify the mechanism of action of different PFAS isomers on the development of DM.
Presentation: Thursday, June 15, 2023