bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU303 The Associations Between Rest-Activity Parameters, Sleep-Disordered Breathing Severity And Glucose Metabolism In Patients With Prediabetes
Authors: Paewponsong Jirayupa , Gerber Ben S , Chirakalwasan Naricha , Saetung Sunee , Anothaisintawee Thunyarat , Reutrakul Sirimon 
Published: October 2023

Abstract
Disclosure: J. Paewponsong: None. B.S. Gerber: None. N. Chirakalwasan: None. S. Saetung: None. T. Anothaisintawee: None. S. Reutrakul: None.
Background: Circadian rhythm abnormalities and sleep-disordered breathing (SDB) can have an adverse effect on glucose metabolism. In addition, studies have suggested that SDB itself could be associated with circadian disruption. This study aimed to determine if circadian characteristics, as measured by rest-activity rhythm parameters, were connected with SDB severity in individuals with prediabetes, and whether rest-activity rhythm parameters were related with glycemia. Methods: A total of 79 patients with prediabetes were enrolled. Actigraphy recordings (Actiwatch 2, Phillips Respironics) spanning 7 days yielded non-parametric rest-activity rhythm parameters and sleep duration. The parameters included M10 (mean activity of the most active 10-h period), L5 (mean activity of the least active 5-h period), intradaily variability (reflecting rhythm fragmentation), interdaily stability (reflecting sleep regularity across days), and relative amplitude (reflecting the activity between M10 and L5 activity). SDB was assessed using an overnight sleep monitor (WatchPAT200). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) were obtained via phlebotomy. Independent predictors of rest-activity rhythm parameters, FBG, and HbA1c were determined using multiple stepwise regression analyses. Model covariates included age, sex, body mass index (BMI), and SDB severity. Results: Increasing SDB severity was associated with lower M10 and greater intradaily variability, but not with FBG, HbA1c or other rest-activity rhythm parameters. After adjusting for age, sex and BMI, increasing SDB severity was independently related with lower M10 (B= -0.102, p=0.001). Further, bivariate analyses showed that a higher HbA1c was associated with a shorter sleep duration, lower relative amplitude, and higher L5. FBG was not related to any rest-activity rhythm parameters. After adjusting for age, sex, BMI and sleep duration, lower relative amplitude, but not L5, was independently related with higher HbA1c (B= −0.027, p=0.031). Conclusion: In prediabetes, a lower relative amplitude, indicating a less robust 24 hour rest-activity rhythm, was associated with a higher HbA1c. These findings suggest that circadian rhythmicity contributes to glycemic control. Greater SDB severity was correlated with decreased activity, but relationships with other rest-activity rhythm parameters were not observed.
Presentation: Thursday, June 15, 2023
THU334 Trends In GLP-1 Agonist Utilization In Diabetics With And Without Vascular Disease
Authors: Sargin Pinar , Barahona Maria , Rubayet Hossain , Leef George 
Published: October 2023

Abstract
Disclosure: P. Sargin: None. M. Barahona: None. H. Rubayet: None. G. Leef: None.
GLP-1 agonists (GLP1) have emerged as a breakthrough class of drugs for the management of Type 2 Diabetes (T2DM). Data from cardiovascular outcomes trials has shown benefits in patients with known atherosclerotic vascular disease, including reduced cardiovascular mortality and stroke. These agents are now considered preferred therapy, however, prior studies have shown low rates of utilization. We hypothesized that recent guidelines and provider education may lead to increased prescribing of GLP1. We analyzed a large, multicenter database to investigate recent trends in GLP1 utilization in patients with T2DM and vascular disease. We extracted all patients from the database with T2DM and excluded patients with diagnoses of Type 1 Diabetes, thyroid cancer, pancreatitis, or MEN syndrome type 2, or age &gt;90. We then stratified the cohort to compare patients with a diagnosis of ischemic heart disease, peripheral vascular disease, or cerebrovascular disease since January 1st, 2021 against diabetic patients without these diagnoses. Patients were compared for rates of prescription of diabetes medications and baseline characteristics including age, sex, race, BMI, HgA1c, and creatinine. Our search generated a total of 408553 patients with T2DM and vascular disease (defined as at least one of the following: ischemic heart disease, peripheral vascular disease, cerebrovascular disease), and 520383 with T2DM and no known vascular disease. The vascular disease cohort was 56% male, 68% white, mean age 70±13. Ischemic heart disease was present in 78%, cerebrovascular disease in 43%, and peripheral vascular disease in 22%. The non-vascular disease cohort was 54% female, 57% white, mean age 63±16. In the vascular disease cohort, 56% were prescribed insulin, 47% metformin, 17% SGLT2, and 14% GLP1. In the non-vascular disease cohort, 43% were prescribed metformin, 32% insulin, 11% GLP1, and 8% SGLT2. The P-value was less than 0.001 for all comparisons. Rates of the utilization of GLP1 agents in our database are still relatively low, but higher than has been reported before. This might suggest a favorable trend compared with prior studies on this topic, although they are not directly comparable due to different patient populations. With only 14% of the T2DM-vascular disease population receiving one of these agents (after excluding those with a documented contraindication), more work needs to be done to enable all patients who would benefit from these medications to access them.
Presentation: Thursday, June 15, 2023
THU343 Potential Association Among Enteroviruses, Acute Flaccid Myelitis And Type 1 Diabetes
Authors: Anh Nguyen Thao , Huynh Ky , Azad Mazieyar , Perdomo Rodriguez Juan Pablo 
Published: October 2023

Abstract
Disclosure: T.A. Nguyen: None. K. Huynh: None. M. Azad: None. J.P. Perdomo Rodriguez: None.
Non-polio enteroviruses, like EV-D68, caused a nationwide outbreak of respiratory illness in the US in 2014, most recently in the fall of 2021. It has been shown that EV-D68 plays a role in causing acute flaccid myelitis (AFM). In addition, the association between enterovirus infections and type 1 diabetes (T1DM) has been widely studied and established. We report a case in which a 19-year-old male consulted for progressively ascending bilateral weakness in the lower extremities. Four weeks prior, he was diagnosed with T1DM and diabetic ketoacidosis (DKA). On exam, he had decreased sensation to light touch, vibration, and temperature below the knees, decreased motor strength 2/5 in bilateral lower extremities, and absence of patellar and Achille reflexes. Thyroid tests, Creatinine Kinase, Aldolase, and vitamin B12 were all normal. Spine MRI showed an enhancement along the L5 and sacral roots. CSF studies were significant for the positive oligoclonal band, the elevated protein level (87gm/dL), and no white blood cell count. CSF gram stain was negative for any organisms. EBV, HSV, and HIV testing were negative. A nonspecific respiratory panel only performed at the time of diagnosis with AFM was negative. The electromyogram did not show any type of acute inflammatory demyelinating polyneuropathy or evidence of myopathy. CT abdomen/pelvis demonstrated mild splenomegaly with small swollen lymph nodes of the periaortic and mesenteric area, which are commonly seen in viral infections. A Digital Subtraction Angiography study did not show any abnormality in spinal vessels. The patient received immunoglobulin and steroid, which was stopped early due to bradycardia and hyperglycemia. Neurology diagnosed the patient with AFM secondary to viral infection, in which the patient may have been infected prior to his diagnosis of DKA. The patient’s weakness resolved, and he was discharged with basal-bolus insulin and is to follow up with neurology and endocrinology outpatient. Enterovirus infection has been associated with T1DM and AFM. While the Respiratory PCR Panel was negative, it was only obtained several weeks after the onset of symptoms. Pathogenesis of extra-respiratory complications of enteroviruses may associate with viremia and systemic dissemination of the virus, which may not be detected by a respiratory PCR panel. Infection by an enterovirus remains the most likely etiology for both immune-mediated disorders, especially during a nationwide outbreak. We recommend providers consider enterovirus infection as a potential cause of AFM, and autoimmune diabetes in order to perform a throughout workup. In a patient with hyperglycemia and flaccid paralysis, T1DM should be suspected.
Presentation: Thursday, June 15, 2023
THU361 Diabetic Ketoacidosis As The Initial Presentation Of Pancreatic Adenocarcinoma, A Case Report
Authors: Siddiqui Usman , Ahmad Mobeen , Raza Shaikh Ali , Rosenberg Daniel 
Published: October 2023

Abstract
Disclosure: U. Siddiqui: None. M. Ahmad: None. A. Shaikh: None. D. Rosenberg: None.
Introduction: Signs and symptoms of pancreatic adenocarcinoma may be vague early in its course and is often discovered when it has quite advanced. Type 2 diabetes has been known to be linked with pancreatic adenocarcinoma with proposed mechanisms of hyperglycemia in these patients including increased insulin resistance, rapid beta cell turnover and oxidative stress. Rarely, diabetic ketoacidosis has been reported as an initial presentation of pancreatic carcinoma. We describe the case of a 61-year-old male with no previous diabetic history presenting with diabetic ketoacidosis (DKA) and found to have pancreatic adenocarcinoma. Case description: A 61-year-old male with no significant past medical history presented to the emergency department (ED) for a one week history of vision changes, nausea, abdominal pain and non-bloody vomiting. He reported heavy alcohol use on weekends, drinking 12 beers a day. He was found to be in DKA with his lab work demonstrating: venous pH 7.0, glucose 717 mg/dL, bicarbonate 7 mmol/L, anion gap 34 and positive beta hydroxybutyrate &gt;60 mg/dL. After fluid resuscitation and IV insulin infusion he eventually had resolution of his DKA. Anti-GAD 65 screen was negative and c-peptide level was 5.71 ng/ml. His hemoglobin A1C was found to be 12.6. CT abdomen-pelvis with contrast demonstrated a patchy hypodensity of with dilation of pancreatic duct and a 2.0 cm pancreatic mass, resulting in pancreatic duct dilation with an MRI confirming these findings. Endoscopic Ultrasound fine needle aspiration confirmed pancreatic adenocarcinoma. The patient proceeded to have distal pancreatectomy and splenectomy. Surgical samples did not show lymph node involvement. After pancreatectomy the patient did have significantly decreased insulin requirements. Discussion: Pancreatic cancer is often discovered late in its course due to its subtle signs and symptoms. Evidence shows that type 2 diabetes is strongly linked with pancreatic cancer, with newly diagnosed type 2 diabetes or glucose intolerance being found in 80% of patients. Insulin resistance caused by pancreatic cancer has been proposed as an etiology of this new-onset diabetes and hyperglycemia. DKA as an initial manifestation of pancreatic cancer, however, is rare. Through this case we hope to highlight this association and suggest, in the right clinical setting, pancreatic cancer workup be considered in adults presenting with new onset type 2 diabetes and DKA.
Presentation: Thursday, June 15, 2023
FRI612 Tirzepatide For The Treatment Of Post-bariatric Surgery Hypoglycemia And Early Dumping Syndrome
Authors: Frederick Stortz Ethan , Margaret Lawler Helen 
Published: October 2023

Abstract
Disclosure: E.F. Stortz: None. H.M. Lawler: Research Investigator; Self; VogenX.
Background: Post-bariatric hypoglycemia (PBH) is a challenging condition with limited treatment options. Glucagon-like peptide 1 (GLP-1) receptor agonists have been used with mixed success. To our knowledge, there have been no reported cases of PBH treatment with dual incretin agonist medications. We describe a case in which tirzepatide was successfully used to improve both post-bariatric surgery hypoglycemia as well as symptoms of early dumping syndrome. Clinical Case: A 46-year-old woman with prediabetes presented with labile blood sugars, post-prandial hypoglycemia, and intermittent severe bloating with diarrhea shortly after eating meals. She had a past medical history of gastric banding 16 years ago, resulting in a 70 pound weight loss. Her post-operative course was complicated by post-meal retching and vomiting for many years. She subsequently had gastric band reversal with concurrent sleeve gastrectomy 2 years ago. While her vomiting improved, she experienced intermittent post-meal bloating and diarrhea. About 8 months after this surgery, she developed symptoms of hypoglycemia after meals, with glucometer readings of 30-49 mg/dL. Continuous glucose monitoring (CGM) for 1 week prior to therapy revealed a time in range (70-180 mg/dL) of 90%, 3-4% time above 180 mg/dL, and 6-7% time below 70 mg/dL. Dietary changes did not help improve hypoglycemic episodes or her dumping symptoms. She initially started tirzepatide 2.5mg weekly and noticed improvement in both symptoms. Her dose increased to 5mg weekly, and she had near complete resolution in her post-prandial hypoglycemia. Upon review of 1 week of CGM data, her time in range improved to 96% with 2% time above 180 mg/dL and 0% time below 70 mg/dL. Her glucose peak was 224 with a nadir of 72. Her early dumping symptoms also improved, occurring only with very high-carb meals. Conclusion: Many pharmacotherapies have sought to improve post-bariatric surgery hypoglycemia with limited success often significant side effects. The post-prandial peak of GLP-1 levels tends to be higher in patients after bariatric surgery compared to obese controls, possibly playing a role in the condition’s pathophysiology. Studies of glucose-dependent insulinotropic peptide (GIP) in patients after bariatric surgery exhibit mixed trends. Numerous case reports have shown successful treatment of PBH with GLP-1 receptor agonists, while other have shown no clear benefit. It is possible that dual incretin therapy may attenuate more of the post-prandial hyperinsulinemic-hypoglycemic response in ways that are incompletely understood and requires further investigation. Interestingly, this case showed that tirzepatide administration not only resulted near-resolution of post-prandial hypoglycemia, but it also improved this patients’ early dumping syndrome symptoms.
Presentation: Friday, June 16, 2023
A Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies
Authors: Srinivasan Shylaja , Wu Peitao , Mercader Josep M , Udler Miriam S , Porneala Bianca C , Bartz Traci M , Floyd James S , Sitlani Colleen , Guo Xiquing , Haessler Jeffrey , Kooperberg Charles , Liu Jun , Ahmad Shahzad , van Duijn Cornelia , Liu Ching-Ti , Goodarzi Mark O , Florez Jose C , Meigs James B , Rotter Jerome I , Rich Stephen S , Dupuis Josée , Leong Aaron 
Published: October 2023

Abstract

Context
Both type 1 diabetes (T1D) and type 2 diabetes (T2D) have significant genetic contributions to risk and understanding their overlap can offer clinical insight.

Objective
We examined whether a T1D polygenic score (PS) was associated with a diagnosis of T2D in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Methods
We constructed a T1D PS using 79 known single nucleotide polymorphisms associated with T1D risk. We analyzed 13 792 T2D cases and 14 169 controls from CHARGE cohorts to determine the association between the T1D PS and T2D prevalence. We validated findings in an independent sample of 2256 T2D cases and 27 052 controls from the Mass General Brigham Biobank (MGB Biobank). As secondary analyses in 5228 T2D cases from CHARGE, we used multivariable regression models to assess the association of the T1D PS with clinical outcomes associated with T1D.

Results
The T1D PS was not associated with T2D both in CHARGE (P = .15) and in the MGB Biobank (P = .87). The partitioned human leukocyte antigens only PS was associated with T2D in CHARGE (OR 1.02 per 1 SD increase in PS, 95% CI 1.01-1.03, P = .006) but not in the MGB Biobank. The T1D PS was weakly associated with insulin use (OR 1.007, 95% CI 1.001-1.012, P = .03) in CHARGE T2D cases but not with other outcomes.

Conclusion
In large biobank samples, a common variant PS for T1D was not consistently associated with prevalent T2D. However, possible heterogeneity in T2D cannot be ruled out and future studies are needed do subphenotyping.
Association of Cerebrovascular Injury and Secondary Vascular Insult With Poor Outcomes After Gunshot Wound to the Head in a Large Civilian Population
Authors: Lamanna Jason J. , Gutierrez Juanmarco , Alawieh Ali , Funk Chadd , Rindler Rima S. , Ahmad Faiz , Howard Brian M. , Gupta Sanjay K. , Gimbel David A. , Smith Randi N. , Pradilla Gustavo , Grossberg Jonathan A. 
Published: October 2023

BACKGROUND AND OBJECTIVES:
Cerebrovascular injury (CVI) after civilian gunshot wound to the head (GSWH) likely contributes to poor outcomes, but little supporting evidence exists. The purpose of this study was to determine whether intracranial CVI from GSWH and secondary vascular insult (stroke or rehemorrhage) were associated with poor outcomes in a large civilian population.

METHODS:
This was a single-institution, retrospective cohort study on patients admitted between January 2014 and July 2022 at a large, metropolitan, level-1 trauma center. Multivariate regression models and propensity score matching were used.

RESULTS:
A total of 512 civilian patients presented with GSWH, and a cohort of 172 (33.5%) met inclusion criteria, with 143 (83.1%) males and a mean (SD) age of 34.3 (±14.2) years. The incidence of intracranial CVI was 50.6% (87/172 patients), and that of secondary vascular insult was 32.2% (28/172 patients). Bifrontal trajectories (adjusted odds ratio [aOR] 13.11; 95% CI 2.45-70.25; P = .003) and the number of lobes traversed by the projectile (aOR 3.18; CI 1.77-5.71; P < .001) were associated with increased odds of resultant CVI. Patients with CVI suffered higher rate of mortality (34% vs 20%; odds ratio [OR] 2.1; CI 0.78-5.85; P = .015) and were less likely to achieve a good functional outcome with a Glasgow Outcome Score of 4–5 (34% vs 68%; OR 0.24; CI 0.1-0.6; P = .004) at follow-up. Furthermore, patients with CVI and resultant secondary vascular insult had even worse functional outcomes (Glasgow Outcome Score 4-5, 16.7% vs 39.0%; aOR 0.012; CI 0.001-0.169, P = .001).

CONCLUSION:
Intracranial CVI from GSWH and associated secondary vascular insult are associated with poor outcomes. Given the high prevalence and potentially reversible nature of these secondary injuries, early screening with vascular imaging and treatment of underlying CVI may prove to be critical to improve outcomes by reducing stroke and rehemorrhage incidence.
A high-sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster
Authors: Nunes Rodrigo Dutra , Drummond-Barbosa Daniela 
Published: October 2023

ABSTRACT
Obesity is linked to reduced fertility in various species, from Drosophila to humans. Considering that obesity is often induced by changes in diet or eating behavior, it remains unclear whether obesity, diet, or both reduce fertility. Here, we show that Drosophila females on a high-sugar diet become rapidly obese and less fertile as a result of increased death of early germline cysts and vitellogenic egg chambers (or follicles). They also have high glycogen, glucose and trehalose levels and develop insulin resistance in their fat bodies (but not ovaries). By contrast, females with adipocyte-specific knockdown of the anti-obesity genes brummer or adipose are obese but have normal fertility. Remarkably, females on a high-sugar diet supplemented with a separate source of water have mostly normal fertility and glucose levels, despite persistent obesity, high glycogen and trehalose levels, and fat body insulin resistance. These findings demonstrate that a high-sugar diet affects specific processes in oogenesis independently of insulin resistance, that high glucose levels correlate with reduced fertility on a high-sugar diet, and that obesity alone does not impair fertility.
Synthesis and Biological Evaluation of Siladenoserinol A Analogs Possessing a Diastereomeric 6,8-Dioxabicyclo[3.2.1]octane Skeleton
Authors: Yoshida Masahito , Sasaoka Kohei , Hano Kohei , Sugiyama Yoshiyuki , Hitora Yuki , Doi Takayuki , Tsukamoto Sachiko , Kigoshi Hideo 
Published: October 2023

Abstract
The efficient synthesis of siladenoserinol analogs possessing a diastereomeric 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) skeleton has been achieved from commercially available carbohydrates as a chiral source. In this synthesis, we successfully determined the reaction conditions for the one-pot transformation using AuCl(PPh3)/AgSbF6/2,6-di-tert-butylpyridine (2,6-DTBP), leading to the desired bicycloketal without losing the TBS group. Elongation of two side chains by the Julia–Kocienski olefination and Horner–Wadsworth–Emmons reaction and subsequent chemoselective sulfamation furnished the two desired diastereomers from the corresponding carbohydrates, respectively. The inhibitory activities of the synthetic diastereomeric analogs against the p53–Hdm2 interaction were slightly weaker than that of natural siladenoserinol A, resulting in the fact that the stereochemistry on the 6,8-DOBCO skeleton would be one of the fundamental factors to control the potency of inhibition of the p53–Hdm2 interaction but not an essential one.
No Evidence of Postactivation Performance Enhancement on Endurance Exercises: A Comprehensive Systematic Review and Meta-analysis
Authors: VASCONCELOS GUSTAVO CÉSAR , BRIETZKE CAYQUE , CESARIO JULIO CESAR SILVA , DOUETTS CARLOS DANIEL BENTO , CANESTRI RAUL , VINICIUS ÍTALO , FRANCO-ALVARENGA PAULO ESTEVÃO , PIRES FLÁVIO OLIVEIRA 
Published: October 2023

ABSTRACT

Purpose
Narrative reviews have suggested that postactivation induced by warm-up routines is effective to increase endurance exercise performance in real-world scenarios. However, systematic reviews with meta-analysis rather than narrative ones are required to provide an up-to-date summary of the evidence and provide directions for practical decisions. Therefore, we systematically reviewed peer-reviewed and gray literature to determine the certainty of evidence and the relative effects of postactivation performance enhancement (PAPE) in endurance exercises.

Methods
The effects of PAPE on endurance performance were meta-analyzed as a standardized mean difference (SMD) from control conditions within a random-effects model considering polled data and subgroups (PAPE strategies, endurance test modalities, and V̇O2max-based endurance level).

Results
Eligible studies (n = 35) showed a high risk of bias due to methodological flaws in randomization and blinding procedures. A meta-analysis including 57 comparisons (432 participants) revealed a significant but very small PAPE effect on endurance performance (Z = 2.49, SMD = 0.15—very small, 95% confidence interval = 0.03 to 0.28) due to exceptional effect sizes reported by two studies (SMD of 2.85 and 2.14). We also observed that neither PAPE strategies nor endurance test modalities or V̇O2max-based endurance levels influenced the PAPE effects on endurance performance. Meta-regression showed that PAPE effects were correlated neither with the time interval between conditioning routines and endurance exercise nor with endurance exercise duration. We found a very low certainty of evidence that PAPE potentiates endurance performance.

Conclusions
Based on the analyses of bias and certainty of evidence, we found no support to recommend PAPE strategies to improve endurance exercise performance. Significant but very small PAPE effects on endurance performance were due to two exceptional effect sizes.