bluuebunny/crossref_metadata_2025_split huggingface dataset:
6486 Gastroparesis Exacerbation by a GLP-1 Agonist
Authors: Deirmenjian Jacqueline M , Dagher Christopher 
Published: October 2024

Abstract
Disclosure: J.M. Deirmenjian: None. C. Dagher: None.
Gastroparesis is characterized by a delay in gastric emptying that may present with nausea, vomiting, satiety, abdominal pain, and anorexia. The most common cause of gastroparesis is diabetes mellitus due to vagal autonomic neuropathy which prevents coordinated gastric contractions. Medications may also induce gastroparesis. Glucagon-like peptide (GLP)- 1 agonists such as semaglutide are being prescribed for diabetes control but also due to benefits of cardiovascular disease and weight loss. Concerns of GLP-1 agonists causing gastroparesis are valid as the mechanism of action includes delaying gastric emptying, especially with newly developed analogs that are more potent with longer half-lives. Patient is a 43-year-old female with a history of hypertension, uncontrolled diabetes mellitus type 2, diabetic gastroparesis, diabetic neuropathy, hyperlipidemia, and obesity who presented with a one-month history of postprandial abdominal pain, nausea, vomiting, and a 40-pound unintentional weight loss with decreased oral intake. Her abdominal pain was sharp and was exacerbated with eating. While she had several gastroparesis flares in the past, she was in remission for almost two years until she was transitioned from dulaglutide to semaglutide after which she had a recurrent flare after two doses. On physical examination, her abdomen was diffusely tender to palpation.On admission, her hemoglobin A1c was 9.7%. She was made NPO, started on peripheral fluids, and initiated on scheduled metoclopramide given high suspicion of a gastroparesis flare. She underwent a gastric emptying study with the gastric amount retained as follows: 97% (at 1 hour), 88% (at 2 hours), and 79% (at 4 hours). Her hospital course was complicated by persistent symptoms of gastroparesis. Gastroenterology recommended scheduled metoclopramide and erythromycin for motility and dietary adjustments including small volume liquid calories. Her oral intake was insufficient and she opted for total peripheral nutrition until symptoms improved. She was advised to never take a GLP-1 agonist again and should her symptoms not improve the next step would be to pursue a gastric pacemaker. The etiology of the patient’s gastroparesis was uncontrolled diabetes. The proximity between starting semaglutide and symptom onset is compelling as an inciting factor in this flare. This admission’s gastric emptying study results showed higher gastric retention for a longer period of time, which may shed light to the potency of these new GLP-1 analogs. The patient tolerated maximum dose dulaglutide for months but not even two doses of semaglutide. With the race to invent more potent GLP-1 agonists for diabetes control and weight loss on the horizon, knowing their side effects and mechanism of action is crucial. While not listed as a contraindication, there should be hesitancy to offer these agents to anyone with significant gastroparesis.
Presentation: 6/2/2024
6680 GLP-1 Agonists in Type 1 Diabetes - Indications and Use
Authors: Panjawatanan Panadeekarn , Radovanovic Natasa , Comi Richard J 
Published: October 2024

Abstract
Disclosure: P. Panjawatanan: None. N. Radovanovic: None. R.J. Comi: None.
Introduction: Insulin therapy is the mainstream treatment in patients with Type 1 diabetes. The use of insulin, though mimicking normal physiology, is associated with weight gain. Glucagon-like peptide 1 (GLP-1) agonists are a class of antidiabetic medication that lowers blood sugar levels and helps promote weight loss. We propose that GLP-1 agonists can reverse the trend of weight gain and help lower hemoglobin A1C (A1C) levels in patients with Type 1 diabetes who were gaining weight. Method: A retrospective chart review was performed at a single institution’s endocrine practice over five years. Patients with Type 1 diabetes with concomitant GLP-1 agonists used for at least one year were included. Observed outcomes were the change in A1C, weight, and basal insulin use compared at baseline, 6 months, and 12 months using mixed models repeated measures. The result was reported as estimated means (95%CI). Statistical significance was determined by a p-value less than 0.05. Results: There were 49 patients included in the study. The mean age was 44.7 years old. There were 32 females (65.3%) and 17 males (34.7%). The mean duration of diabetes was 24.6 years. Thirty-five patients (71.4%) used insulin pumps, and fourteen (28.6%) were on multiple daily injections. Overall, patients had been gaining an average of 2.0 kg per year. After the treatment with GLP-1 agonists, weight was significantly reduced at 12 months (90.0 kg (95%CI 84.9-95.1), p&lt;0.001) compared to baseline (97.6 kg (95%CI 92.7-102.5)). The A1C was significantly improved at 12 months (7.6% (95%CI 7.2-7.9), p&lt;0.001) compared to the baseline (8.2% (95%CI 7.9-8.6)). Total daily basal dose was significantly reduced at 12 months (35.8 units (95%CI 29.8-41.9), p&lt;0.001) compared to the baseline (39.2 units (95%CI 33.3-45.1)). The improvement in the parameters was more pronounced at 6 months after treatment but persisted at 12 months. Conclusion: Weight gain is a consequence of insulin usage in both Type 1 and Type 2 diabetes, which considerably impacts treatment outcomes and the development of comorbidities. We conclude that GLP-1 agonists are helpful to reverse the trend of weight gain and help lower A1C levels in patients with Type 1 diabetes who require life-long insulin treatment.
Presentation: 6/3/2024
6494 GLP-1/GIP/Glucagon Triagonist Improves Glycemic Control via Gαq Signaling Pathway and TRPM5 Activation
Authors: Khajavi N , Schreier P C , Beyerle P , Reinach P S , Breit A , Boekhoff I , Müller T D , Gudermann T 
Published: October 2024

Abstract
Disclosure: N. Khajavi: None. P.C. Schreier: None. P. Beyerle: None. P.S. Reinach: None. A. Breit: None. I. Boekhoff: None. T.D. Müller: Grant Recipient; Self; Novo Nordisk. Speaker; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. T. Gudermann: None.
Cutting-edge research on obesity and diabetes strives to pioneer innovative drug combinations targeting various dysfunctional metabolic regulatory pathways. The single-molecule triagonist has been developed to directly interact with the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GcgR). It provides a breakthrough in the treatment of obesity and type 2 diabetes because of greater efficacy compared to conventional single-agonist therapy. While the triagonist is already undergoing phase two clinical trials, the downstream mechanism requires further study. Previously, we showed that triagonist elicits transient rises in intracellular Ca2+ concentration that augment glucose-induced rises in insulin secretion in murine (MIN6) and human (1.1B4) pancreatic β cell lines. Although Gαs signaling is known as the main mediator of both GLP-1 and GIP signaling, our research indicates that the superior effect of the triagonist on insulin secretion is not solely dependent on the activation of the classical Gαs pathway and the exchange factor activated by cAMP (EPAC) signaling. Instead, we report that the triagonist enhances glucose-induced rises in insulin secretion via Gαq signaling and its downstream effector, the TRPM5 channel. This involvement is evident, as blocking Gαq signaling with a specific blocker, YM254890, reduced triagonist-induced rises in insulin secretion in mouse pancreatic islets. Similarly, blocking TRPM5 with the TPPO blocker attenuated triagonist-induced increases in insulin secretion and Ca2+ signaling in mouse pancreatic islets. Strikingly, both blockers had no remarkable impact on GLP-1- and GIP-induced rises in insulin secretion. Our in vivo analysis demonstrates that the triagonist improves glucose tolerance in diet-induced obese wild-type mice, but this effect was absent in TRPM5 knockout mice. Notably, the triagonist augments glucose-induced insulin secretion in isolated islets of wild-type mice more than treatment with GLP1 and GIP mono-agonists. Furthermore, this enhanced response is absent in TRPM5 knockout islets. Recent studies propose that persistent membrane depolarization of β cells leads to a switch from Gαs to Gαq signaling, which is a major amplifying pathway of insulin secretion under diabetic conditions. Our study shows that the enhancing effect of the triagonist, acting as a biased agonist, on insulin secretion is dependent on TRPM5 activation through the Gαq signaling pathway.
Presentation: 6/2/2024
12567 Hybrid Closed-loop Insulin Pumps' Role In CFRD Management: A Retrospective Case Series Analysis
Authors: Yaseen Ibrahim , Slattery David 
Published: October 2024

Abstract
Disclosure: I. Yaseen: None. D. Slattery: None.
Cystic fibrosis-related diabetes (CFRD) significantly burdens individuals with cystic fibrosis (CF), notably influencing their health longevity and quality of life. This case series retrospectively examines the effects of hybrid closed-loop (HCL) insulin pump therapy on CFRD management strategies. We reviewed clinical data from 8 CFRD patients between the ages of 19-37 who were transitioned to HCL insulin pump therapy over a three-month interval. Seven patients managed their condition with the Control IQ system, combining the Tandem t:slim insulin pump with the Dexcom G6 CGM sensor . One patient employed the Medtronic MiniMed™ 780G system, coupled with a Guardian 4 sensor. Our analytical survey spanned across multiple health metrics pre- and post-HCL therapy initiation, including hemoglobin A1c (HbA1c) levels, percentage of time in the target glucose range, hypoglycemic event frequency, FEV1 scores from pulmonary function tests, body mass index (BMI), and CF-specific quality of life (CFQ-R) scores. The findings highlighted a considerable decline in HbA1c, with averages falling from 73.71 mmol/mol at baseline to 56.6 mmol/mol in five patients at the conclusion of the three-month treatment follow-up. Three patients are pending another HbA1c evaluation despite routine virtual clinical follow-ups. Hypoglycemia was uncommon, consistently &lt;1% both pre- and post-intervention. Within the available data, time in target glucose range impressively increased from 39.10% before to 63.8% after pump application. For three patients, pulmonary function test results indicated either maintenance or marginal improvement; assessments for the other participants are still upcoming. An average BMI increase of 1.5 kg/m² signals positive implications for patients' nutritional health. While comprehensive CFQ-R outcome assessments are ongoing, preliminary indications suggest progress. Concluding, this case series highlights the advantageous role of HCL insulin pumps in enhancing glycemic control and curbing glucose fluctuations in CFRD without increasing hypoglycemia risks. The uplift in nutritional status with no adverse impact on pulmonary function endorses the HCL approach as effective in CFRD treatment protocols. These promising short-term outcomes advocate for extended research and analysis, with a focus on substantiating long-term clinical benefits.
Presentation: 6/1/2024
8772 Impact of Stress Hyperglycemia on Individuals Hospitalized for COVID-19 with and without Diabetes
Authors: Burguera-Couce Ella , Cheng Vicky Ong , Monteiro Joao Filipe G , Gopalakrishnan Geetha 
Published: October 2024

Abstract
Disclosure: E. Burguera-Couce: None. V.O. Cheng: None. J.G. Monteiro: None. G. Gopalakrishnan: None.
Background: Stress hyperglycemia (SH), the physiologic increase in blood glucose during severe illness, has been linked with poor outcomes in certain disease states1. Hyperglycemia in the setting of diabetes (DM) has been well established as a predictor of poor outcomes in Coronavirus disease 2019 (COVID-19) infection2-4. The impact of SH on health outcomes for individuals without DM (NoDM) hospitalized with COVID-19 infection is less clear with studies reporting variable outcomes in this population4-6. Objective: To evaluate the impact of SH on health outcomes among hospitalized individuals with COVID-19Methods: Data from 1001 individuals with SH (defined as ≥ 2 instances of BG above 180 mg/dL) admitted in Rhode Island with COVID-19 infection during the first-wave (March 1-June 30, 2020) and second-wave (July 1, 2020-February 28, 2021) was analyzed. Multivariate logistic regression was conducted to compare DM status for length of stay (LOS), ICU admission, mechanical ventilation (MV) and in-hospital mortality, and was adjusted for age, race/ethnicity, gender, insurance, and wave. Model investigating risk factors associated with poor outcomes (ICU admission, MV or in-hospital mortality) in hospitalized individuals with SH was additionally adjusted to include BMI, Chronic kidney disease (CKD), hypertension (HTN), pulmonary disease, and cardiovascular diseases. Results: 17.0% (170) of the cohort had NoDM. Average age (67.6±13.9), gender (57.1% male) and race/ethnicity (Caucasian/White 48.9%, Hispanic 28.0%, Black 13.2% and Other 10.0%) noted in the overall cohort. Individuals with NoDM were more likely to be Caucasian/White (57.7 vs 47.1%, p-value=0.0122), and more likely to require LOS ≥1-week (OR 2.32[1.57-3.44]), ICU admission (2.26[1.60-3.20]) and MV (3.39[2.35-4.89]). NoDM was also associated with higher in-hospital mortality (3.44[2.39-4.96]). The risk of poor outcomes was significantly higher in NoDM compared to DM (ICU admission 47.7 vs 28.6%, MV 45.3 vs 20.1%, Mortality 41.8 vs. 18.2%). In multivariate analysis, Caucasians/Whites (0.50[0.29-0.87]) were less likely to have poor outcomes than the other races. NoDM (3.55[2.40-5.25]), male gender (1.57[1.16-2.13]), CKD stage 5 (1.94[1.40-2.68]), and admission during the first-wave (2.64[1.89-3.70]) were identified as independent risk factors for poor outcomes in SH associated with COVID-19. Conclusion: Our study showed that individuals without a known diagnosis of diabetes hospitalized with COVID-19 who experienced SH during their hospital course had worse outcomes when compared to individuals with diabetes and hyperglycemia. NoDM, male gender, nonwhite race/ethnicity, CKD stage 5 and admission during the first wave were identified as independent risk factors for poor outcomes in COVID-19 hospitalizations with hyperglycemia.
Presentation: 6/1/2024
8000 Intestinimonas Butyriciproducens As A New Preventive Therapy For Type 2 Diabetes: a Proof Of Concept Randomized Controlled Trial
Authors: Antoniotti Valentina , Caputo Marina , Mollero Edoardo Luigi Maria , Antonioli Alessandro , Tini Sabrina , Manfredi Marcello , Gul Sahin , Bui Nam , Seegers Jos , De Vos Willem M , Aimaretti Gianluca , Prodam Flavia 
Published: October 2024

Abstract
Disclosure: V. Antoniotti: None. M. Caputo: None. E. Mollero: None. A. Antonioli: None. S. Tini: None. M. Manfredi: None. S. Gul: None. N. Bui: None. J. Seegers: None. W. De Vos: None. G. Aimaretti: None. F. Prodam: None.
Background. The incidence of type 2 Diabetes Mellitus (T2D) is increasing worldwide. Prevention is possible by changing lifestyle but it’s not effective alone in real life, due to poor compliance over time. New strategies are necessary, mostly for high-risk individuals. Therapeutic microbiology is a further proposed target, and butyrate-producing bacteria can improve metabolic parameters in obese patients. Our study aims to evaluate the effect of Intestinimonas butyriciproducens as a preventive therapy for T2D in prediabetes thanks to its effects in decreasing Advanced Glycation End Products (AGEs), converting sugars and proteins in butyrate, and increasing insulin sensitivity.Methods. The trial is a double-blind, randomized, placebo-controlled (phase 1) and open-label pilot study with two different doses (phase 2) of 26 weeks. I. butyriciproducens (105 CFU/day) or placebo were given for 12 weeks, then subjects in placebo will start the treatment (105 CFU/day), and the other group will increase the dose (108 CFU/day) for 14 weeks. Overweight or obese patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were included. Patients were assessed for clinical, biochemical, and microbiota parameters at the time of recruitment (V1), after phase 1 (V7) and phase 2 (V10), during which the eating and lifestyle habits were also evaluated. No dietary advice was given. Results. Nineteen have completed the study. Treated patients during the first phase had a significant improvement in glucose-insulin metabolism demonstrated through the HOMA Disposition Index (p= 0.0075). Lipid profile also ameliorates in patients treated at a low dose and then at a high dose, particularly decreasing triglycerides (phase 1: p= 0.0212; phase 2: p= 0.0261). The weight and BMI of patients were stable throughout the period of study. Data from Flash glucose Monitoring (FGM) show a more stable glucose, mainly at the end of the study. Serum AGE concentrations showed a trend towards a decrease in treated patients, whereas IL-10 slowly increased without changes in IL-6 and IL-17.Lastly, 10 out of 19 patients after 26 weeks of treatment had a remission in IFG or IGT (52.6%). Conclusions. Intestinimonas butyriciproducens seems to improve insulin sensitivity and triglycerides in treated patients. Intestinimonas butyriciproducens could be a new strategy in the work-up of T2D prevention.
Presentation: 6/1/2024
8074 Investigating Viral Infections, Systemic Inflammation, and their Complex Interplay in Type 1 Diabetes Pathogenesis
Authors: Girdhar K , Elko E , Pina A , Atkinson M , Ludvigsson J , Ladner J , Altindis E 
Published: October 2024

Abstract
Disclosure: K. Girdhar: None. E. Elko: None. A. Pina: None. M. Atkinson: None. J. Ludvigsson: None. J. Ladner: None. E. Altindis: None.
Type 1 diabetes (T1D) is an autoimmune disorder characterized by the immune-mediated destruction of insulin-producing beta cells. The etiological factors triggering the immunogenicity of endogenous β-cell antigens remain a focal point of investigation. Viral infections, particularly enteroviruses, coxsackieviruses, and rotaviruses, have been proposed as potential contributors to T1D onset and progression. However, the causal relationship between viral infections and T1D pathogenesis remains elusive. To address this, we conducted an in-depth analysis of viral infection histories of T1D patients and pediatric T1D progressors compared to the controls. To this end, we employed highly multiplexed serology using PepSeq sequencing, an in vitro platform designed for conducting proteomic assays against customizable targets via DNA-barcoded peptides. Utilizing samples from the All Babies in Sweden (ABIS) study (n=58) and the TrialNet study (n=116 new-onset T1D, n=25 established T1D, n=128 controls), we assessed seropositivity against 79 different human viruses. Contrary to previous reports, no significant differences were identified in viral infection histories between T1D individuals and controls. Subsequent analyses of enriched Peptide Count and Viral Homology Search (VHS) species provided further confirmation of the absence of distinctions in T1D progression. Next, we determined whether there are any differences in the markers of systematic inflammation in spite of their similar viral history profile. Therefore, we employed Luminex assays to investigate cytokine profiles in established T1D individuals (n=25). While we could not identify any differences when we compared T1D patients to controls, we identified notable sex-specific differences. Anti-inflammatory cytokines (IL-4, IL-13, IL-22) were lower in female T1D patients compared to female controls. Likewise, female T1D patients had higher pro-inflammatory cytokines (IL-17E, TNF-β). On the other hand, male T1D patients exhibited increased levels of epidermal growth factor and platelet-derived growth factor compared to male controls, with IL-22 uniquely elevated. Our findings challenge the direct association between viral infections and T1D, highlighting the importance of investigating alternative factors. Moreover, the observed sex-specific cytokine alterations underscore the complex interplay between immune responses and T1D, emphasizing the need for sex-specific therapeutic strategies. This research contributes valuable insights into the intricate dynamics of viral infections, systemic inflammation, and their potential roles in T1D pathogenesis.
Presentation: 6/2/2024
12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus
Authors: Chacon Cruz Marcos E , Gonzalez Bossolo Alex N , Mora Osoria Gabriel Jose 
Published: October 2024

Abstract
Disclosure: M.E. Chacon Cruz: None. A.N. Gonzalez Bossolo: None. G.J. Mora Osoria: None.
A number of dietary patterns have been proposed as an effective method for weight reduction. A keto diet is a strict low-carbohydrate and high-fat diet. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. However, a serious but rare complication of the ketogenic diet is ketoacidosis associated with low carbohydrate intake, which should be cautiously monitored in people with a predisposition to the condition, such patient with diabetes mellitus type 1. We report the case of a female patient living with type 1 diabetes mellitus female who developed her first episodes of diabetic ketoacidosis (DKA) as the following the course of ketogenic diet. A 53 y/o Female patient with past medical history diabetes mellitus type 1 and pernicious anemia went emergency department complaining pelvic pain associated with weakness, nausea and vomiting for about 1 day of evolution. Patient also refers that during the past 2 weeks she has been doing a detox and taking some herbal and tea. Other physical examinations were unremarkable except for moderate dehydration. The initial testing revealed patients meet criteria for severe diabetes ketoacidosis (DKA) with a pH: 7.04, CO2 15, serum central bicarbonate in 6 mmol/L and elevated blood glucose in 504 mg/dl and positive urine and serum ketones, C-Peptide less than 0.02 ng/ml. and glycosylated hemoglobin in 8.25%. She was admitted to the intensive care unit and treated with intravenous saline, intravenous insulin infusion, and electrolyte repletion. Blood glucose levels and metabolic acidosis improved. After DKA resolved patient refers that week started with Keto-diet and was restricting carbohydrates. Patient was discharge home with multiple injection insulin and followed by Endocrinologist services in the external clinic for a follow up. This case illustrates the challenges and the importance of dietary history providing clues to the diagnosis. If we had never asked her about her diet, we would not have found the reason that brought her to the DKA. This case demonstrates the development of DKA following ketogenic diet in a patient with type 1 diabetes. It is important for physicians to be aware of this rare potential complication of ketogenic diet which is infrequently reported in literature. Therefore, physicians should be cognizant of the complications and risks, and benefits of the ketogenic diet. Risks and benefits of the ketogenic diet should be discussed with patients before initiation of this diet. The patient was followed in an outpatient clinic with Endocrinologist service for evaluation for an insulin pump.
Presentation: 6/1/2024