bluuebunny/crossref_metadata_2025_split huggingface dataset:
6900 Fetal Abdominal Obesity in Women Exhibiting One Abnormal Value on Diagnostic Testing for Gestational Diabetes Mellitus
Authors: Kim Wonjin , Park Soo Kyung , Kim Yoo Lee 
Published: October 2024

Abstract
Disclosure: W. Kim: None. S. Park: None. Y. Kim: None.
Background: Fetal abdominal obesity (FAO) was already observed at the time of diagnosis of GDM in our previous study. We investigated whether fetuses of women with hyperglycemia milder than GDM showed accelerated abdominal growth, leading to adverse pregnancy outcomes. Methods: We retrospectively reviewed the medical records of 7,569 singleton pregnant women who were universally screened using a 50-g glucose challenge test (GCT) and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT result was ≥140mg/dL. GDM, one value abnormality (OVA), and normal glucose tolerance (NGT, NGT1: GCT negative, NGT2: GCT positive & OGTT negative) were diagnosed using Carpenter-Coustan criteria. With fetal biometry data measured simultaneously with 50-g GCT, relative fetal abdominal overgrowth was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference(AC) per actual GA by the last menstruation period(LMP), biparietal diameter (BPD) or femur length(FL), respectively. FAO was defined as FAOR ≥90th percentile Results: The FAORs of GA-AC/GA-LMP and GA-AC/GA-BPD were significantly higher in OVA subjects compared to NGT subjects but not in NGT2 subjects. Although the frequency of FAO in OVA (12.1%) was between that of NGT (9.6%) and GDM (18.3%) without statistically significant difference, the prevalence of large for gestational age at birth and primary cesarean delivery rates were significantly higher in OVA (9.8% and 29.7%) than in NGT (5.1% and 21.5%, p&lt;0.05). Particularly, among OVA subjects with FAO, the prevalence (33.3% and 66.7%) was significantly higher than in those without FAO (9.7% and 24.2%, p&lt;0.05). Conclusion: The degree of fetal abdominal growth acceleration in OVA subjects was intermediate between that of NGT and GDM subjects. OVA subjects with FAO at the time of GDM diagnosis were strongly associated with adverse pregnancy outcomes.
Presentation: 6/2/2024
6656 Frequently sampled HbA1c Shows Low-Sodium, High-Carbohydrate Rice Diet To Be Effective in Type 2 Diabetes
Authors: Neelon Francis A , Sanoff Scott , Lin Pao-Hwa 
Published: October 2024

Abstract
Disclosure: F.A. Neelon: None. S. Sanoff: None. P. Lin: None.
Hemoglobin and glucose react to form HbA1c, which persists until red blood cells (RBCs) are removed from circulation. Since RBCs survive approximately 122 days, HbA1c is usually measured at intervals of months to years, but more frequent measurement can illuminate changes in blood glucose (BG). We used Beach’s equation for the kinetics of HbA1c formation, to construct graphical depictions of how HbA1c should decline over the 122 days after a drop from constantly high to constantly normal BG levels. As part of routine patient care (not an experimental protocol), we measured HbA1c at 2-4-week intervals in a convenience sample of 10 patients (one of whom was evaluated on 2 occasions) with Type 2 diabetes, obesity, and elevated HbA1c who attended the now defunct Rice Diet Program (RDP) in Durham, NC. All were fed 3 meals/day, comprising 800-1000 kcal of rice, fruits, grains, and vegetables (70-90% carbohydrates) and 300 mg of sodium. Two patients were initially taking insulin; 1, glipizide; and 1, sitagliptin, exenatide, metformin; all hypoglycemic agents were eventually discontinued, and none added. Mean initial HbA1c of 9.7% (range, 8.3-11.7) fell to a mean of 6.2% (range 5.3-8.4) after a mean of 82 days (range, 41-139). Variability in final HbA1c values reflects, at least in part, variable duration of voluntary residence at the RDP. In 9 patients, HbA1c declined in close accordance with the course predicted for complete normalization of blood glucose from the very start of the diet; in 1 patient, HbA1c declined slowly for 25 days, after which the rate increased to near that for complete normalization of BG. Plots of Hb1c values extrapolate back through the point of origin, implying normalization of BG occurs within days of starting the RDP, and is maintained thereafter. Data from frequent measurement of HbA1c show: 1) Normalization of BG occurs almost immediately upon dietary restriction, implying that hyperglycemia in Type 2 diabetes is driven by daily calorie excess, not by accumulated calorie excess (ie, obesity). 2) Contrary to some misperceptions, a high-carbohydrate, sodium- and calorie-restricted diet is not deleterious to ― and may actually benefit ― glucose control in Type 2 diabetes.
Presentation: 6/3/2024
7555 Gender-Related Differences in Outcomes of Patients With Diabetic Ketoacidosis: An Analysis of the National Readmission Database
Authors: Ahsan E , Lesniak C , Akula M , Hu k , Chalasani K , Ong R , Holland S , Hossain M , Cheng J , Heaton J 
Published: October 2024

Abstract
Disclosure: E. Ahsan: None. C. Lesniak: None. M. Akula: None. K. Hu: None. K. Chalasani: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. J. Heaton: None.
Introduction: Diabetic ketoacidosis (DKA), one of the most serious complications of diabetes, is a significant cause of morbidity and mortality. Hospitalizations for DKA have increased significantly over the past two decades. Despite this, there is a notable absence of data on gender-related variations in the clinical characteristics and outcomes of individuals hospitalized with DKA. Understanding these distinctions is crucial for optimizing disease prevention and care. Thus, the primary aim of this study was to explore whether gender influences the outcomes of DKA. Methodology: We analyzed the National Readmissions Database (NRD) from 2016 to 2020 by evaluating patients admitted with a primary diagnosis of DKA without coma. Patients were included if they were at least 18 years old and admitted between January and November. Patients meeting inclusion criteria were stratified by sex. The groups were assessed for 30-day readmissions, all causes of mortality, length of stay, and total cost. Descriptive statistics, Cox proportional hazards, and adjusted Wald tests were used to compare the groups. Results: Between 2016 and 2020, 642,431 patients met the inclusion criteria with a median age of 44, of which 46.5% were female and 53.5% were male. Early readmission occurred in 33,639.20 females and 31,101.92 males. Cox regression analysis showed a significant difference in readmission risk for female patients than males (HR 1.20, 95% CI 1.17-1.22, P = &lt;0.001). The length of stay was higher in male patients than in female patients (adjusted Wald test, P =&lt;0.001). Inpatient mortality was higher in females than in males (Cox regression analysis, P = 0.009). Total cost was higher in males compared to females (adjusted Wald test, P = &lt;0.001). Conclusion: Regrettably, the majority of studies on diabetic ketoacidosis (DKA) have not given due attention to gender differences. Our study, however, reveals statistically significant variations in in-hospital mortality and 30-day readmission rates between men and women hospitalized with DKA, with women exhibiting higher rates than men. Additionally, the length of stay and total cost were found to be higher for men. To comprehend the underlying reasons for these distinctions, further investigations are warranted. Early introduction and intensification of insulin therapy may prove beneficial for this patient group in mitigating the risk of DKA and other complications associated with diabetes mellitus.
Presentation: 6/2/2024
8731 Glucose homeostasis remains normal across a range of adiposity in fit men and women
Authors: Potter A W , Chin G C , Jacques J I , Nindl L J , Looney D P , Tharion W J , Chapman C L , Halford E N , Friedl K E 
Published: October 2024

Abstract
Disclosure: A.W. Potter: None. G.C. Chin: None. J.I. Jacques: None. L.J. Nindl: None. D.P. Looney: None. W.J. Tharion: None. C.L. Chapman: None. E.N. Halford: None. K.E. Friedl: None.
Introduction. Glucose dysregulation is a major obesity-related comorbidity, affecting mental and physical performance. Glycated hemoglobin (HbA1c) is a validated and stable biomarker representing glucose regulation over 2-3 months. Nearly half of American adults (41%) have elevated HbA1c concentrations representing prediabetes (≥5.7%). In a large cross-sectional sampling of the American population, HbA1c becomes elevated in 33% of individuals at &gt;24% body fat (BF) (men) and &gt;38%BF (women). However, daily physical activity is an important moderator of metabolic health and adiposity - the “fit fat” concept. We evaluated this effect in physically active men and women. Methods. Body composition and metabolic health data were obtained from 36,392 adults (18,130 men and 18,262 women) in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018, for comparison of %BF and HbA1c relationships. Body composition and HbA1c data were obtained from 220 healthy and physically fit active-duty military men and women (188 men, mean ± SD (range): age 25.7 ± 5.9 (18-53) years; height 176.3 ± 7.7 (154.0-201.1) cm; body mass 85.3 ± 11.9 (55.7-134.7) kg, maximal oxygen uptake (VO2max) 49.1 ± 11.9 (33.8-62.5) ml/kg/min; 32 women, age 26.5 ± 7.0 (19-45) years; height 161.4 ± 5.9 (147.1-172.8) cm; body mass 63.9 ± 8.3 (46.7-86.6) kg, VO2max 42.5 ± 8.3 (29.1-52.6) ml/kg/min). Body composition was measured using DXA (iDXA, General Electric Healthcare, Madison, WI) and HbA1c was measured from capillary blood samples using a validated point-of-care analyzer (DCA Vantage Analyzer, Siemens Medical Solutions USA, Inc, Malvern, PA). Results. HbA1c remained within the normal range (&lt;5.7%) for 98% (216/220) of a relatively wide range of %BF in a group of men (9-36%) and women (21-46%) who engaged in daily physical activity. This sample included 64 men (34%) and 4 women (12.5%) that exceeded the 24 and 38%BF thresholds where clinically high HbA1c concentrations have been observed in the civilian population. From this subset, none of the assessed women had HbA1c ≥5.7%. Three men had HbA1c 5.7-5.8% and also high measured physical fitness (VO2max, 50.1-62.5 ml/kg/min) and low %BF (15-17%); while one had lower physical fitness (VO2max 43.87 ml/kg/min) and higher body fat (26%) (HbA1c 6%). Conclusion. Glucose homeostasis remains within normal values across a range of adiposity in fit men and women. These data support the importance of daily physical activity in mitigating elevations in HbA1c, even in individuals with increased relative body fat. Physical activity appears to have a protective effect for metabolism.
Presentation: 6/3/2024
9227 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer
Authors: Viesi Carlos 
Published: October 2024

Abstract
Disclosure: Carlos Viesi, Ph.D.[1], Ian Tamburini, BS[1], Hosung Bae, Ph.D[1]., Erwin Ilegems, Ph.D.[2], Leandro Velez, Ph.D. [1], Mingqi Zhou, BS[1], Christy Nguyen, Ph.D.[1], Casey Johnson, Ph.D.[1], Cholsoon Jang, Ph.D[1]., Erika Nishimura[2] and Marcus Seldin, Ph.D.[1]. [1]Department of Biological Chemistry, Center for Epigenetics and Metabolism, University of California, Irvine, CA, USA, [2]Departments of Diabetes Protein Engineering, Diabetes Biology & Pharmacology, Medicinal Chemistry, Protein Engineering, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
Type 2 Diabetes (T2D) affects over 530 million people around the globe. Insulin resistance, encompassing tissues such as muscle, adipose, and liver, is the initial step hallmarked by hyperinsulinemia. Coupled with β-cell failure, these coordinated responses progress to T2D, becoming irreversible and medically challenging. Despite the well-established requirement for communication between pancreas and peripheral tissues in T2D progression, this area remains almost entirely unexplored. Here, we performed a human population genetic screening across 310 individuals to search for new endocrine regulators of pancreas function. Specifically, global gene expression from 18 peripheral tissues was analyzed to identify potential endocrine regulators of insulin secretion. This analysis prioritized liver-specific Haptoglobin-related protein (HPR) as genetically-enriched with islet insulin responses. Mouse models using AAV technology and acute protein administration of HPR showed that this newly secreted protein is sufficient to prevent diet-induced insulin resistance through enhanced beta-cell respiration. When mice were administered soluble HPR, then pancreatic tissue subjected to global RNA-sequencing, enhanced respiration pathways were observed. Next, we generated hepatocyte-specific overexpression models using AAV, which were sufficient to rescue whole-body glucose disposal profiles and weight gain in diet-induced insulin-resistant mice. Altogether, these findings highlight HPR as a novel soluble protein which signals from liver to pancreatic islets.
Presentation: 6/3/2024
9369 Hyperglycemia On Admission And The Risk Of Complications In Patients With Hip Fractures
Authors: Hassan A , Almardini S , Arafa F , Aoun L 
Published: October 2024

Abstract
Disclosure: A. Hassan: None. S. Almardini: None. F. Arafa: None. L. Aoun: None.
Hyperglycemia is associated with medical complications such as poor wound healing, immunocompromised state, prolonged hospital stay, and even death. Studies have shown that patients with type II diabetes who sustain a hip fracture have an increased risk of mortality, presumably due to the increased risk of post-operative complications like postoperative pneumonia, deep surgical site infections, and postoperative delirium. Our study aims to determine if initial glucose on admission can be used as a prognostic factor for 30-day mortality and 30-day readmission in patients presenting with hip/femur fractures who also underwent surgical repair. All patients admitted to the Northwell hospital system between 6/2022 and 7/2023 for hip/femur fractures and underwent a surgical repair above the age of 50 were analyzed for this retrospective chart review study. Patients were divided into three groups based on the initial glucose value derived from BMP/CMP (ranges: glucose &lt;140, glucose 140-200, and glucose &gt;200). Higher glucose ranges were used as patients fasting status could not be determined. In each glucose range group, we analyzed 30-day mortality and 30-day readmission rate. Logistic regression was utilized to assess the odds of 30-day mortality and 30-day readmission as a function of initial glucose levels on admission, adjusting for BMI category, malnutrition status, and CKD stage. Adjusted odds ratios and 95% confidence intervals were computed. The original dataset contained 3158 observations. After excluding patients that did not receive a surgical intervention during their stay (n = 752), the sample size decreased to 2406. There were 50 patients that had been admitted twice during the study period, the second visit excluded from analysis, bringing the final sample size to 2356 subjects.Initial glucose on admission was not significantly associated with 30-day mortality (p = 0.8), or with 30-day readmission (p = 0.9) after adjusting for malnutrition status, BMI, and CKD. Based on the Hosmer and Lemeshow Goodness-of-Fit Test, the data fit the model well for the 30-day mortality but poorly for the 30-day readmission. Despite the well-established associations between hyperglycemia and adverse health outcomes, our study did not identify a significant association between initial glucose on admission and 30-day mortality or 30-day readmission, even after adjusting for factors such as malnutrition status, BMI, and CKD. The lack of statistical significance in the adjusted analyses suggests that other factors may play a more substantial role in predicting these outcomes in the specified patient population.
Presentation: 6/2/2024
9247 Identification of Novel Therapies for Monogenic Diabetes Using Connectivity Map (CMap)
Authors: Kreienkamp Raymond Joseph , Dos Santos Felipe R C , Bryan Christopher , Florez Jose Carlos , Claussnitzer Melina , Udler Miriam S 
Published: October 2024

Abstract
Disclosure: R.J. Kreienkamp: None. F.R. Dos Santos: None. C. Bryan: None. J.C. Florez: None. M. Claussnitzer: None. M.S. Udler: None.
Monogenic diabetes is an underdiagnosed form of diabetes that is caused by DNA variation of strong effect in a single gene. While it is an exciting area for targeted drug development, as some forms of monogenic diabetes can be treated with gene-specific therapies, there are currently few targeted therapies available. Additionally, existing treatments are not able to cure or modify the underlying disease. Therefore, to identify novel disease-modifying therapies, we leveraged CMap, a data resource developed at the Broad Institute of MIT and Harvard that contains over one million gene expression signatures from treatment of cell types with perturbagens including drugs, bioactive small molecules, gene overexpression, and gene knockdown reagents. We analyzed the connectivity, i.e. the similarity, between two gene expression signatures, to search for perturbagen gene expression signatures opposing gene expression changes associated with monogenic diabetes. We were able to identify 15 classes of medications with significantly enriched connectivity with HNF1A-knockdown. Included in these classes were sulfonylureas, which are known to have preferential therapeutic benefit for this specific condition, supporting this method for drug discovery. Other medications included HDAC inhibitors, tyrosine kinase inhibitors, and riboflavin. We also surveyed other genes causing monogenic syndromes that include diabetes, such as PPARG, where CMap indicated high connectivity with thiazolidinediones, a type 2 diabetes drug class with known mechanism targeting PPARγ, opposing PPARγ-knockdown and beneficial for treating patients with PPARγ-driven familial partial lipodystrophy. We then validated CMap results in a high-fidelity cellular model system - primary human adipocytes constitutively expressing Cas9 - using a high-dimensional metabolic disease oriented read-out LipocyteProfiler for systematic image-based profiling of cellular phenotypes in metabolic cell types. To establish causality between the causal monogenic target PPARG and its agonizing compound effect, we performed a targeted CRISPR-Cas9 based knockout of PPARG in human adipocytes, and linked changes at the cellular level to changes related to thiazolidinediones. The data revealed a striking association between the PPARγ perturbation and the TZD effect, along with an increasing CMap absolute value and LipocyteProfiler connectivity (p=9.8 E-6). Our findings support the use of expression signature mapping as a novel approach for identifying therapies for monogenic diabetes. Further exploration of databases like CMap and validation of identified medication classes could lead to new pharmacological treatments for diabetes.
Presentation: 6/2/2024
7760 Identifying Conventional and Novel Biomarkers to Predict Checkpoint Inhibitor Associated Autoimmune Diabetes
Authors: Wu L , Wentworth J , Liddle C , Carlino M , Brown D , Clifton-Bligh R J , Long G , Sasson S , Tsang V , Menzies A , Gunton J E 
Published: October 2024

Abstract
Disclosure: L. Wu: None. J. Wentworth: None. C. Liddle: None. M. Carlino: Consulting Fee; Self; Amgen Inc, Bristol-Myers Squibb, Novartis Pharmaceuticals, Pierre Fabre, Regeneron Pharmaceuticals, Roche Pharmaceuticals, Merck, Sanofi. D. Brown: None. R.J. Clifton-Bligh: None. G. Long: Consulting Fee; Self; Amgen Inc, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis Pharmaceuticals, Pierre Fabre, Regeneron Pharmaceuticals, Sandoz. S. Sasson: None. V. Tsang: None. A. Menzies: Consulting Fee; Self; Bristol-Myers Squibb, Novartis Pharmaceuticals, Roche Pharmaceuticals, Pierre Fabre. J.E. Gunton: None.
Introduction: Checkpoint inhibitor associated autoimmune diabetes (CIADM) is a rare but highly morbid complication of immune checkpoint inhibitor (ICI) therapy. As indications for ICIs expand, the ability to predict CIADM has huge potential value and has yet to extensively explored. Aims: To identify potential biomarkers for prediction of CIADM in patients commencing ICI therapy. Methods: 14 patients with metastatic melanoma treated with ICI who subsequently developed CIADM were identified. 28 matched controls were identified (matched for ICI type, gender, cancer response and other immune related adverse events). Pre-treatment, on ICI and post CIADM serum and PBMCs were analysed. Serum was analysed for type 1 diabetes autoantibodies, C-peptide, glucose and an immune cytokine panel of TNFα, IL-2, IL-4, IL-6, IL-10, CXCL10, IL-1β, CCL2, IL-17A, CXCL8, TGF-B1, and IL-12p70. PBMCs were sorted using a BD Influx III cell sorter into 1000 CD8 cell subsets per sample. RNA was extracted and sequenced using a NovaSeq X with approximately 10 million 150bp paired end reads. RNA-Seq analysis was performed using edgeR. Results: Pre-ICI-treatment anti-GAD had a positive predictive value for CIADM prediction of 63.6% and a negative predictive value of 82.1%. Anti-IA2, anti-IAA and anti-ZnT8 were not predictive. C-peptide fell rapidly from 1.8nmol/L on treatment to 0.18nmol/L post diagnosis for CIADM and remains normal in controls. There were no significant differences in circulating cytokines between CIADM patients and controls. Pathway enrichment analysis performed on differentially expressed genes in people who developed CIADM identified significant regulation in pathways for B cell receptor and interferon signalling, RAS signalling and IGF1R signalling. These changes were not observed in controls. Conclusion: Anti-GAD has some predictive value for CIADM, but is incompletely sensitive. Further research is needed to prospectively test the predictive value of GAD Ab in combination with other potential markers such as pancreatic volumetry as we have previously published.
Presentation: 6/2/2024