bluuebunny/crossref_metadata_2025 huggingface dataset:
7360 An Overlooked Cause of Hypoglycemia and Weight Loss: Phosphodiesterase-4 Inhibitors
Authors: Aurora John , Cappetta Kate , Lechan Ronald M
Published: October 2024

Disclosure: J. Aurora: None. K. Cappetta: None. R.M. Lechan: None.

Background: Phosphodiesterase-4 (PDE-4) inhibitors, apremilast and roflumilast, are anti-inflammatory agents used to treat psoriasis, psoriatic arthritis, and COPD. These agents are commonly associated with gastrointestinal intolerance. However, patients may also experience profound weight loss (>10%). We present a case of a patient with T2DM who developed significant hypoglycemia and weight loss on apremilast. Clinical Case: A 57-year-old female with T2DM, obesity, psoriasis, and postsurgical hypothyroidism due to papillary thyroid cancer developed symptoms of hypoglycemia and weight loss over 1 month. Prior to this, her A1c was 7.8% and weight 104 kg on stable doses of metformin, repaglinide, and insulin glargine. Insulin glargine and repaglinide were both discontinued given her symptoms, yet hypoglycemia persisted, and she continued to lose weight. Further investigations into the cause of this sudden change were carried out. Initial fasting labs: BG 53 mg/dL, C-peptide 4.48 ng/mL (RR 0.8-3.85 ng/mL), insulin 12.8 uIU/mL (RR <18.4 uIU/mL), proinsulin 29.8 pmol/L (RR <18.8 pmol/L), A1c 6.8%, cortisol 24.9 mcg/dL (RR 4-22 mcg/dL), IGF-1 95 ng/mL (Z-score -0.7), and IGF-2 434 ng/mL (RR 267-616 ng/mL). 1 month later, hypoglycemia symptoms improved but she continued to lose weight. Fasting labs were repeated: BG 84 mg/dL, C-peptide 5.62 ng/mL, insulin 24.3 uIU/mL, proinsulin 35 pmol/L, and beta-hydroxybutyrate (BHB) 0.17 mmol/L (RR <0.28 mmol/L); metformin was subsequently stopped. A MR abdomen revealed a 2 cm cystic pancreatic lesion that showed atypical mucinous epithelium by biopsy under endoscopic ultrasound guidance. Gallium-68 DOTATATE-PET scan was unremarkable for an insulin-producing tumor. Two months off metformin, she had no further episodes of hypoglycemia, but her weight loss continued. Fasting labs were repeated: BG 129 mg/dL, C-peptide 5.15 ng/mL, insulin 18.2 uIU/mL, proinsulin 40.5 pmol/L, and BHB 0.27 mmol/L. Review of her medications identified apremilast as a potential culprit contributing to both her hypoglycemia and weight loss, as her symptoms started 1 month after starting apremilast. Over 9 months using apremilast, her A1c decreased by 1% and weight decreased by 27%. Hypoglycemia resolved off all glucose-lowering agents. Conclusion: Significant weight loss with apremilast may be explained by PDE-4 inhibition increasing cyclic AMP, which triggers the release of GLP-1 with subsequent effects on pancreatic beta cells. Apremilast has also been shown to significantly increase fasting insulin levels in patients without insulin resistance, as seen in our patient (1). Given these effects, patients may be at higher risk of hypoglycemia with concurrent glucose-lowering agents, particularly secretagogues. BG and weight need careful monitoring for patients with T2DM using PDE-4 inhibitors. Reference: 1. Ikumi K, et al. J Dermatol. 2022;49(4):e125-e126.

Presentation: 6/3/2024
7753 Anoctamin 4 in the Area Postrema Regulates Glucose and Energy Homeostasis
Authors: Tu L , Xu Y
Published: October 2024

Disclosure: L. Tu: None. Y. Xu: None.

Located on the floor of the 4th ventricle within the dorsal surface of the medulla oblongata, the area postrema (AP) is a circumventricular organ where a proper blood-brain barrier is missing. Numerous studies reveal that neurons in the AP are implicated into suppression of food intake (e.g., glucagon-like peptide 1 (GLP-1)-mediated anorexia), but the role of AP neurons in whole-body glucose homeostasis is less investigated. Here we identified and fully characterized the physiological functions of anoctamin-4 (Ano4, a calcium activated chloride channel)1 in the AP. CRISPR-mediated deletion of Ano4 in the AP caused a lower body weight and reduced blood glucose, concurrent with an improved glucose tolerance and increased insulin sensitivity. Chemogenetic activation of Ano4-expressing neurons in the AP (APAno4) increased food intake and blood glucose, and did not induce conditioned flavor avoidance. Both Ano4 neurons and non-Ano4 neurons (i.e., neurons do not express Ano4) sent projections to the lateral parabrachial nucleus (LPBN). Optogenetic stimulation of APAno4 ◊ LPBN circuit promoted feeding behavior and increased blood glucose, whereas stimulation of APnon-Ano4 ◊ LPBN circuit inhibited food intake and did not influence glucose homeostasis. Finally, RNAscope studies reveal that 45.7% of APAno4 neurons are glutamatergic neurons, and 41.8% of them are GABAergic neurons. Furthermore, APAno4 neurons showed only a 2.6% overlap with Glp-1r-expressing neurons in the AP, but had a 60.8% co-localization with protein tyrosine phosphatase receptor δ2, which serves as orexigenic asprosin receptor. Together, our results indicate that Ano4 neurons in the AP are the first reported orexigenic neurons, and represent potential therapeutic targets for human diseases with glucose imbalance and abnormal feeding behavior. Reference: (1) Tu, L. et al. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. J Clin Invest 133,14. (2023). (2) Mishra, I. et al. Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor. Cell Metab 34, 549-563. (2022).

Presentation: 6/2/2024
6413 Anti-PD1 induces T1D in an HLA-DQ8, HLA-A2.1 mouse model
Authors: Houeiss P , luce S , Boitard C
Published: October 2024

Disclosure: P. Houeiss: None. S. luce: None. C. Boitard: None.

Anti-PD1 is an immune checkpoint inhibitor that has revolutionized cancer treatment. It blocks the interaction between PD1, a receptor on the surface of activated or exhausted T cells, and its ligands PDL1 and PDL2, to inhibit the immune response. However, anti-PD1 induces T1D in 0.4-2% of patients raising questions about the risk factors and the mechanisms behind T1D development. Since the pancreas of these patients is inaccessible, we focus on autoimmune diabetes induction in a transgenic mouse model modified to express the T1D susceptibility genes HLA-DQ8, HLA-A2.1 and the human preproinsulin and on identifying new targets to prevent or treat this disease. Thus, 8 to 12 weeks old mice were treated initially with 500 micrograms of anti-PD1 followed by 250 micrograms every other day for 10 days. Control mice received 6 injections of PBS. Mice were followed up for evidence of hyperglycemia for 60 days. Cells and tissues from the pancreas, and the spleens were isolated 15-, 30- or 60-days post-treatment initiation and analyzed by flow cytometry and immunohistochemistry. Although diabetes incidence in treated mice was 14% (n=14), insulitis incidence progressively increased over time reaching 86% on D60 (p=0.005). On Day 15, in the spleen, a significant 10% increase of CD4+Foxp3+CD25- T cells at the expense of the CD4+Foxp3- T cells were seen in the treatment group as compared to the control (37.1±4.25 vs 26±3.5, p<0.01, n=5 per group). In the treatment group, PD1 expression significantly increased on CD4+Foxp3+ T cells whereas PDL1 expression increased on CD4+Foxp3- and CD8+ T cells (p<0.01). On D30, in the pancreas, infiltrates show positive staining for F4/80+, CD4+ and CD8+ T cells with scarce foxp3+ T cells. While the absolute percentage of CD4+Foxp3+ T cells increased in the insulitis and diabetes group, their percentage among CD3+ T cells decreased in the insulitis (10.2%) and diabetes group (3.9%) as compared to the control group (13.5%). Infiltrates were concentrated around the islets and the efferent and afferent vessels, and extended to the exocrine pancreas, leading to secondary acinar destruction. In the pancreatic infiltrates from anti-PD1 treated mice, we noted a significant increase in CD4+ T cells recognizing Ins13-21 monomers as compared to the negative control. PD1 blockade induced an insulitis characterized by a Treg to effector T cells imbalance. Thus, it acted on the early phase of T1D. In conclusion, this model describes a new T1D endotype that shares similarities with ICI induced diabetes in patients.

Presentation: 6/2/2024
6531 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy
Authors: Nassar Mahmoud , Abosheaishaa Hazem , Dandona Paresh , Ghanim Husam , Chaudhuri Ajay
Published: October 2024

Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation.

Presentation: 6/1/2024
8626 Associations Between Low Serum Bilirubin Levels and the Progression of Diabetic Kidney Disease in Individuals with Type 2 Diabetes, Including Those in a Normoalbuminuric State
Authors: Kim Eun Sook , Cho Yunjung , Hong Oak-Kee , Jo Kwanhoon , Han Je-Ho , Moon Sungdae
Published: October 2024

Disclosure: E. Kim: None. Y. Cho: None. O. Hong: None. K. Jo: None. J. Han: None. S. Moon: None.

Objective: This study aimed to investigate the potential correlation between serum bilirubin levels and the progression of diabetic nephropathy, assessing whether low serum bilirubin levels are associated with a decline in renal function, while considering the baseline albumin excretion status. Methods: The longitudinal observation, spanning 11 years, involved 1167 Korean subjects aged 20 years or older, diagnosed with type 2 diabetes mellitus (T2DM), and having a baseline estimated glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m2. Albuminuria was assessed by the 24-hour urinary albumin to creatinine excretion rate (ACR) and categorized into normoalbuminuria (ACR <30 mg/g), micro- or macroalbuminuria (ACR >300/g). Cox regression analysis was employed to explore connections between serum bilirubin levels and eGFR decline ≥40%, with adjustments for potential confounding variables. Results: Over a median follow-up of 8.2 years, 128 individuals experienced a decline in eGFR >40%. The hazard ratio (HR) of incident GFR decline was 1.72 (95% CI: 1.04-2.85, P=0.036) in the lowest total bilirubin (TB) tertile compared to the highest TB tertile after multivariable adjustment. When stratified by baseline albuminuria status, low bilirubin levels were significantly associated with eGFR decline, even in the normoalbuminuria group (HR: 2.21, 95% CI: 1.26-3.90, P=0.006), with a gradually increasing risk according to the absence of low TB levels and albuminuria (HR: 2.92, 95% CI: 1.65-5.19, P<0.001), and low TB levels and albuminuria (HR: 3.01, 95% CI: 1.65-5.46, P<0.001). Conclusion: Low serum TB levels are associated with an increased risk of rapid GFR decline in Korean patients with T2DM. Serum bilirubin levels may serve as a prognostic marker for the development and progression of diabetic kidney disease.

Presentation: 6/1/2024
9332 Breathless Struggle: Unraveling The Interplay Between DKA And Acute Respiratory Distress Syndrome
Authors: Zahra Sundas , Subramani Rashmi , Abbas Mubashir , Hasan Khwaja Yusuf , Manas F N U , Bajracharya Charu
Published: October 2024

Disclosure: S. Zahra: None. R. Subramani: None. M. Abbas: None. K.Y. Hasan: None. F. Manas: None. C. Bajracharya: None.

Introduction: Diabetic Ketoacidosis (DKA) is a life threatening emergency with mortality rate of 0.15%-0.30%. Acute Respiratory Distress Syndrome (ARDS) is a rare complication of DKA which presents as a sudden onset of dyspnea and progressive hypoxia. It is an inflammatory process that damages the alveolar-capillary membrane leading to the fluid leakage into the alveolar space. The incidence of ARDS in DKA remains unknown. It is more commonly seen in adolescents and young adults. The exact pathogenesis of ARDS in DKA is currently unknown. Some proposed mechanisms are that a severe metabolic acidosis in DKA along with increased cytokines production due to long standing hyperglycemia leads to increased capillary membrane permeability allowing fluid to accumulate in the alveolar space. TNF-a and IL-6 along with other pro-inflammatory cytokines are known to cause endothelial damage and increase pulmonary permeability leading to pulmonary edema. However most DKA patients with severe metabolic acidosis do not develop ARDS. Case Presentation:Case 1: A 19 year old male with uncontrolled type I diabetes mellitus presented with altered mental status. On examination, he was tachycardic and tachypneic with dry mucous membranes. Lab workup revealed leukocytosis, severe hyperglycemia, and severe anion gap metabolic acidosis with beta hydroxybutyrate level of 14.20 mmol/L (normal: 0.02-0.27 mmol/L). He was diagnosed with DKA and started on intravenous fluids, and insulin as per institutional DKA protocol. Approximately 12 hours post-admission, the patient experienced sudden-onset dyspnea with deteriorating hypoxia, necessitating emergent intubation and mechanical ventilation. Chest radiography displayed bilateral patchy ground-glass opacifications consistent with acute respiratory distress syndrome (ARDS). Despite the administration of 8 liters of intravenous fluids, the patient exhibited a negative net fluid balance of 2.3 liters, implicating fluid shift. Further investigations, including bronchoscopy and bronchoalveolar lavage, revealed an unobstructed airway, minimal secretions, and no evidence of hemorrhage or infection. Comprehensive infectious work-ups yielded negative results as well, reinforcing the diagnosis of DKA as the underlying cause of ARDS. Conclusion: Acute Respiratory Distress Syndrome is a rare but potentially fatal complication of Diabetic Ketoacidosis. Early recognition of this serious pulmonary complication of DKA and its prompt management is essential to prevent respiratory failure and mortality.

Presentation: 6/1/2024
12340 Cardiovascular Risks With Testosterone Replacement Therapy In Patients With Type 2 Diabetes Mellitus
Authors: Gupta Archit , Nassar Mahmoud , Ghanim Husam
Published: October 2024

Disclosure: A. Gupta: None. M. Nassar: None. H. Ghanim: None.

Background: Concerns have been raised about testosterone replacement therapy (TRT) in hypogonadism patients, particularly regarding cardiovascular disease (CVD) risk. Despite some studies showing TRT's non-inferiority to placebo in men at high CVD risk, its impact on patients with type 2 diabetes mellitus (T2DM) remains uncertain. This study examines the incidence of cardiovascular events in patients with T2DM on TRT, with a focus on the first four years of treatment. Methods: Utilizing the TriNetX electronic health records network, this retrospective cohort study targeted patients with T2DM with testosterone levels <300 ng/dl or diagnosed hypogonadism. Patients were divided into two main groups based on their CVD history and TRT status. We conducted a comparative analysis between each cohort and a control group of patients who did not get testosterone replacement therapy (TRT). Matching for age, HbA1C, and BMI created balanced cohorts for comparison: 39,589 in each of the non-CVD event cohorts and 16,065 in each of the CVD event cohorts. Results: In patients without prior CVD, TRT significantly reduced the risk of acute myocardial infarction (MI) (risk ratio: 0.765, p <0.0001), with no significant difference in cerebral infarction risk. Conversely, TRT increased the risk of acute MI (risk ratio: 1.164, p < 0.0001) and cerebral infarction (risk ratio: 1.177, p < 0.0001) in patients with a history of CVD.Discussion: TRT may decrease acute MI risk in patients with T2DM without prior CVD but elevate acute MI and stroke risks in those with a CVD history. These findings suggest the need for cautious TRT consideration in patients with T2DM with differing cardiovascular histories. Conclusion: This analysis reveals that TRT is associated with a decreased risk of acute myocardial infarction in patients with T2DM without a history of CVD, suggesting a potential protective effect in this subgroup. However, TRT increases the risk of both myocardial infarction and stroke in patients with a prior history of CVD, indicating the need for careful patient selection and monitoring. These findings highlight the significance of personalized evaluation in the administration of TRT, particularly in patients with T2DM who have different cardiovascular backgrounds, to balance benefits against potential risks.

Presentation: 6/2/2024
8150 CD1a Lipid Presentation Contributes to T2D Phenotype in DIO Mouse Model
Authors: Ayala Angulo J A , Wiggins K D , Lopez M , Nicholas D
Published: October 2024

Disclosure: J.A. Ayala Angulo: None. K.D. Wiggins: None. M. Lopez: None. D. Nicholas: None.

Type 2 Diabetes’s complex etiology, progression, and comorbidities are not fully explained by current models. Elevation of inflammatory markers and immune cell infiltration into tissues of T2D patients has been described in the literature extensively, but no clear answers as to what antigens are driving this response and how these observations contribute to disease progression exist. Recently, CD1a has been shown to present lipids to T cells and induce a memory response. Our previous work shows that T2D patients produce anti-lipid antibodies likely derived with T cell help, not present in healthy patients. Together, these data suggest a potential role for lipid-specific T cell responses to drive T2D progression through inflammatory stress, antibody production, and tissue infiltration. Current work with human CD1a transgenic B6 mice points to elevated liver steatosis and hepatitis along with higher glucose levels relative to low fat diet controls. CD1a mice show smaller islets suggesting pancreatic atrophy. This validates the CD1a-T cell mechanism as a potential contributor to T2D but also introduces a more physiologically relevant mouse model of T2D.

Presentation: 6/1/2024
9271 Cholinergic Signaling in the Mouse Embryonic Pancreas Targets Early Endocrine Cells
Authors: Duarte Carolina , Panzer Julia Katharina , Borowsky Nicholas , Caicedo Alejandro
Published: October 2024

Disclosure: C. Duarte: None. J.K. Panzer: None. N. Borowsky: None. A. Caicedo: None.

The parasympathetic vagus nerve affects pancreas function by activating local intrapancreatic neurons that release acetylcholine (ACh). These neurons are derived from progenitors of the vagal neural crest and colonize the pancreas during embryonic development. The specific mechanisms by which ACh is released from these neurons influence embryonic development of the islet and, specifically, beta cells remain largely unknown. The purpose of this study was to identify cholinergic signaling components and assess early physiological responses to ACh during murine development of endocrine lineage cells. We extracted pancreatic rudiments from mice at embryonic stages E15 to E18 and stained them for neuronal and endocrine markers, along with components associated with cholinergic signaling. We further performed Ca2+ imaging of the pancreatic rudiments from NGN3CRE-GCaMP3 mice to record responses to ACh in cells of the endocrine lineage. At E15, we observed a significantly higher concentration of glucagon+ cells compared to insulin+ cells, consistent with the earlier differentiation of alpha cells in the developing pancreas. Neuronal body clusters were identified in close proximity to endocrine lineage cells from E15 to E18, with the neuronal network becoming more dispersed and interconnected. At E15, wide distribution of the presynaptic vesicular acetylcholine transporter (VAChT) was observed later becoming localized around insulin+ and glucagon+ cells at E18. Postsynaptic acetylcholinesterase (AChE) colocalized with glucagon+ cells from E15 to E18 and with insulin+ cells by E18. ACh elicited Ca2+ responses in individual endocrine cells as early as E15. Our results show that cholinergic nerve terminals target early endocrine cells and elicit responses to ACh, indicating that local cholinergic neurons innervate and activate endocrine progenitors in the embryonic pancreas. Our current studies are aimed at determining how cholinergic signaling contributes to beta cell differentiation and function. We expect this knowledge to guide future protocols for deriving beta cells from stem cells.

Presentation: 6/2/2024
7890 Combination of Dorzagliatin and Canagliflozin Improves β-cell Function and Alleviates Hepatic Steatosis in db/db Mice
Authors: Zhang Ziyue , Chen Shanshan , Ji Shuhui , Zhao Qinying , Qiao Jingting , Liu Ming
Published: October 2024

Disclosure: Z. Zhang: None. S. Chen: None. S. Ji: None. Q. Zhao: None. J. Qiao: None. M. Liu: None.

Introduction: Early combination of anti-hyperglycemic medications with different targets is an optimal choice for patients with type 2 diabetes (T2D) who do not achieve targeted HbA1c with monotherapy. Dorzagliatin is a novel dual-acting glucokinase activator that has been shown to be effective in both drug-naive and metformin-treated patients with T2D. However, the effect of combination of dorzagliatin and sodium-glucose cotransporter-2 inhibitor (SGLT2i) remains unknown. Methods: Ten-week-old db/db mice were treated daily with either dorzagliatin (30mg/kg of body weight) alone, or canagliflozin (30mg/kg of body weight) alone, or dorzagliatin plus canagliflozin, or vehicle only by gavage for 6 weeks. Body weight and fasting blood glucose were monitored weekly. Plasma insulin, triglyceride, and cholesterol were measured every two weeks. The morphology of islets and liver was evaluated by chemical staining and immunofluorescence. Results: The 6-week treatment of dorzagliatin had no significant effect on fasting blood glucose and fasting plasma insulin but reduced body weight in db/db mice compared to those treated with vehicle. It also caused a significant decrease of islet size and β-cell number. Surprisingly, dorzagliatin alleviated hepatic steatosis but did not affect serum lipid levels. The combination of dorzagliatin and canagliflozin lowed fasting blood glucose and improved glucose tolerance without affecting bodyweight, and the anti-diabetic effect was stronger than the canagliflozin-only treatment group. Combination treatment group also showed an increased islet size and β-cell number, and alleviated liver steatosis compared with vehicle group. Conclusion: The combination of dorzagliatin and canagliflozin had better antidiabetic effects than single-agent administration, providing clinical guidance for the combination therapy of dorzagliatin and SGLT2i in the treatment of type 2 diabetes.

Presentation: 6/2/2024
6844 Comparison of Lactated Ringers and Normal Saline in the Treatment of Diabetic Ketoacidosis
Authors: Johnson Jake N , Drincic Andjela T , Nein Kaitlyn , Buddenhagen Emma , Samson Kaeli , Langenhan Trek
Published: October 2024

Disclosure: J.N. Johnson: None. A.T. Drincic: None. K. Nein: None. E. Buddenhagen: None. K. Samson: None. T. Langenhan: None.

Background: Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. We hypothesized that the use of LR compared to NS for volume management in DKA will shorten time to DKA resolution, reduce time to DKA associated protocol insulin infusion discontinuation, and result in lower post-intravenous fluid resuscitation chloride values. Methods: We conducted a single institution, retrospective cohort study of patients admitted with the diagnosis of DKA following our institution’s transition from NS to lactated ringers (LR) as the default resuscitative and maintenance fluid in our DKA management protocol. Adult patients admitted with DKA before and after the protocol change were identified. The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol continuous insulin infusion. Results: Of 246 patients meeting inclusion criteria, 119 were stratified to the NS group (pre-protocol change) and 127 to the LR group (post-protocol change). T-test analysis revealed decreased time to DKA resolution in the LR group (mean 17.1 hours; SD 11.02) relative to the NS group (mean 20.6 hours; SD 12.22; p = .02). Duration of DKA protocol continuous intravenous insulin was shorter in the LR group (mean 16.0 hours; SD 8.72) compared to the NS group (mean 21.4 hours; SD 12.50; p = 0.0001). Conclusions: In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol continuous insulin infusion.

Presentation: 6/2/2024
6745 Complete Remission of Type 1 Diabetes and the Honeymoon Phase: A Case Report
Authors: Krinsky Dana , Brutsaert Erika , Mullally Jamie Ann
Published: October 2024

Disclosure: D. Krinsky: None. E. Brutsaert: None. J.A. Mullally: None.

Introduction: Type 1 Diabetes (T1D) is a chronic autoimmune disease resulting in insulin deficiency from pancreatic beta-cell destruction. Recent evidence suggests that it can be a partially relapsing and remitting disease, with some patients with T1D being able to briefly discontinue insulin early in the disease course. This phenomenon has been referred to as the “honeymoon phase.” While this period tends to be short, on the order of weeks to months, we describe a unique case of a patient with T1D with a long remission, lasting about five years. Clinical Case A 21-year-old Mexican-American male (BMI 26) with past medical history of T1D presented with polyuria and a 50-pound unintentional weight loss over a 6-month period. He was first diagnosed with T1D at age 14 years when his Hemoglobin A1c (HbA1C) was 13.3% (normal range 4.0-5.6%) in the setting of hospitalization for diabetic ketoacidosis (DKA). All antibody testing done at that time was negative, but islet cell antibodies were later found to be positive. Insulin therapy was started, weaned, and then completely discontinued at age 16 when the patient’s HbA1c was normal at 5%. The patient had no symptoms of diabetes until 6 months prior to presenting, seven years after his original diagnosis. He was found to be in DKA with a HbA1c >14%. Additionally, insulin (< 3.0; normal range 6-27) and c-peptide (0.43; normal range 0.81-3.85) were low with an elevated glucose of 366. Insulin autoantibody, GAD-65 antibody, and islet cell antibody were negative. His DKA resolved and he was discharged on basal and nutritional insulin. Conclusion: The physiology of the honeymoon phase is not well understood and there is not a clear definition, although stimulated C-peptide levels, insulin requirements, and calculating insulin dose adjusted A1c (IDAA1c) have been commonly used. There is variability in reports of the prevalence of partial remission (PR), estimated to occur in 22-60% of patients, with an average duration of 9 months. Our case is unique in that the patient was diagnosed with T1D at the age of 14 years but was able to discontinue all insulin for five years. His presentation is consistent with a complete remission with insulin independence and normal glycemic control (HbA1C <6%) without the use of hypoglycemic agents. Complete remission has a prevalence of only 6.5%. Prior data has shown factors associated with diabetes remission include male sex, postpubescent age of diabetes onset, and fewer than two positive antibodies; factors seen with our patient. Our case highlights a very long remission of T1D, and a better understanding of the immunologic and metabolic factors at play in the honeymoon phase may pave the way for novel T1D prevention and treatment strategies.

Presentation: 6/2/2024
8189 Demographics and Healthcare Utilization of Diabetic Versus Non-Diabetic Gastroparesis hospitalization in the United States Using the National Inpatient Sample database
Authors: Khan Shahryar , Zia Laila , Khan Mashal Alam , Amin Muhammad Kashif , Khan Muhammad Atif , Sattar Farhan
Published: October 2024

Disclosure: S. Khan: None. L. Zia: None. M. Khan: None. M. Amin: None. M. Khan: None. F. Sattar: None.

Background: Gastroparesis is commonly associated with neuropathy secondary to Diabetes and Non-Diabetic causes such as Idiopathic, Post-Viral and Surgical with a wide spectrum of clinical manifestations impairing quality of life, worsening morbidity, and mortality. The purpose of this study is to assess Demographic disparities and utilization of healthcare services between Diabetic (DG) Versus Non-Diabetic Gastroparesis (NDG) admissions. Methods: Data were extracted from the National Inpatient Sample Database for the year 2020. It comprises discharge data obtained from a 20% stratified sample of community hospitals across the country. We conducted a retrospective cohort study focusing on admissions of patients aged 18 years and above with diagnosis of DG and NDG were identified using ICD-10 codes. Multivariate regression analysis was used to estimate the Mean difference of the Average length of hospital stay (LOS), and total hospital charges (THC). Multivariate logistic and linear regression was used accordingly to adjust for confounders. Analysis was performed using STATA 18. Results: Our study identified 10330 patients hospitalized due to gastroparesis, among them 1446 (14%) had DG. Hospitalizations with DG in comparison with NDG had lower number of women (65% Vs 80.7%, P≤0.05), a higher proportion of black adults (36.5% Vs 17%), a lower proportion of white adults (46.4% Vs 70%), and a higher Charlson Comorbidity Index. In DG, 104(7.19%) patients had EGD and non-diabetic gastroparesis, 977 (11%) had EGD during admission. The mean LOS in hospital was 4.72 days and mean total hospital charges were 51327 USD. Comparing both cohorts, there was statistically significant decrease in the mean LOS in DG, Adjusted Mean difference of 1.27 days (P = 0.006). In addition, there was significant decrease in the total cost of hospitalization with an adjusted Mean difference of 13832 (P=0.001). Thirty patients with NDG died during hospital course and none with Diabetic gastroparesis. Conclusion: According to our findings, majority of admissions with gastroparesis are related with non-diabetic causes with higher healthcare utilization and mortality rate. Gastroparesis is a relatively frequent and poorly understood condition which needs considerate effort to have a better understanding of disease.

Presentation: 6/2/2024
7252 Difference between interstitial and blood glucose during glucose loading is associated with the degree of insulin resistance in subjects with prediabetes and type 2 diabetes
Authors: Kim Doohwa , Ryang Soree , Im Myungsoo , Kim Jeongmi , Kim Yeongjin , kim Youngjin , ha Joon , Kim Jinmi , Kim Sangsoo
Published: October 2024

Disclosure: D. Kim: None. S. Ryang: None. M. Im: None. J. Kim: None. Y. Kim: None. Y. kim: None. J. ha: None. J. Kim: None. S. Kim: None.

Background and Aims: This study investigated the main factors responsible for the differences between blood glucose (BG) and interstitial fluid glucose (ISF) during glucose loading. Methods: A total of 204 Korean subjects without history of type 2 diabetes were enrolled. The subjects were categorized into three groups according to diabetes criteria by American Diabetes Association; NGT (normal glucose tolerance, n=36), PreDM (prediabetes, n=130) and T2D (undiagnosed type 2 diabetes, n=38). For glucose monitoring, a CGM (continuous glucose monitoring) system (Dexcom G6, Dexcom, San Diego, USA) was attached for 10 days. 75g oral glucose tolerance test (OGTT) was performed during applying CGM with stabilization (after wear of 3 days). Blood sample collected at t=0, 30, 60, 90 and 120 min for glucose and insulin concentration. Two parameters [insulin sensitivity (mIS) and beta-cell function (mBCF)] were derived novel mathematical model. Results: Among NGT, PreDM and T2D, there are heterogeneity in the difference and pattern between BG and ISF in this study. We identified the probability density function of BG - ISF across glucose tolerance, there is a trend that the means of BG - ISF with G60, 90, and 120 move to the right, as glucose tolerance status changes NGT to PreDM and DM. BG - ISF is significantly associated with insulin resistance (R=0.32, p<0.001), not diminished beta cell function. Conclusions: Because individuals vary in their degree of insulin resistance as a primary pathophysiology of type 2 diabetes, the caution should be needed in interpreting the glycemic response of CGM after a glucose load.

Presentation: 6/3/2024
9390 Does Znt8a Have An Association With The Duration Of Diabetes? Case Series And Literature Review
Authors: Rivera Vargas Natalie Marie , Botero Suarez Carlos S , Suryanarayanan Sowmya K , Saad-Omer Suhail
Published: October 2024

Disclosure: N.M. Rivera Vargas: None. C.S. Botero Suarez: None. S.K. Suryanarayanan: None. S. Saad-Omer: None.

Context: Latent autoimmune Diabetes of adults (LADA) is a form of autoimmune diabetes with features of Type 2 Diabetes but positive autoantibodies resembling Type 1 Diabetes. Latent autoimmune diabetes in adults (LADA), has a mixed phenotype with positive islet-cell antibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), protein tyrosine phosphatase autoantibodies (IA2A), insulin autoantibodies (IAA), or zinc transporter-8 autoantibodies (ZnT8A). Since the discovery of ZnT8A, the relevance and clinical utility of this marker has sparked interest. Although ZnT8A is used as a complementary diagnostic aid in children, its utility in adults seems to be unclear. Objective: We report a case series of 26 subjects referred to the Orlando VA Endocrine clinic with measured ZnT8A. We hypothesize that higher ZnT8A will be found in adult autoimmune diabetes with newly diagnosed diabetes rather than those with a longer duration of diabetes. We also explore the association between ZnT8A and family history, duration of diabetes, diabetes complications, and C-peptide levels. Method: A case series of 26 adult patients with diabetes mellitus with a positive ZnT8A (≥15 U/mL). We reviewed medical records of these cases to include ZnT8A levels, years of diabetes diagnosis, C-peptide levels, and diabetes complications. Patients were classified into subgroups based on ZnT8A levels into < 350 U/mL or ≥ 350 U/mL. Results: The 26 patients reviewed had a mean (SD) age of 46 (13) years. The mean (SD) duration of diabetes was 16 (12) years, and HbA1C was 8.4 (1.1) %. Poisson regression analysis showed a statistically significant inverse relationship between ZnT8A and years of diabetes (regression coefficient: -0.028; 95% confidence interval: -0.03 to -0.25; p-value <0.001). Diabetic ketoacidosis was present in 35% of subjects, while diabetic neuropathy was noted in 58% of subjects with positive ZnT8A. Patients with a high ZnT8Ab above 350 U/mL displayed a weak trend towards a lower C-peptide mean (p-value 0.42), and lower prevalence of DKA (p-value 0.42) which was not statistically significant. Conclusion: In this case series of patients with adult-onset diabetes, there seems to be a statistically significant inverse relationship between ZnT8A levels and duration of diabetes suggesting a reduction of ZnT8A levels over time. Although limited by a small number of subjects, this may suggest the need for screening with autoantibodies in the setting of diabetes earlier in the disease process.

Presentation: 6/2/2024
12239 Effect Of Nano2, A Donor Of Nitric Oxide, On Glucose Mediated Oxidative Stress In Pancreaticb-cells
Authors: Islam Kazi Nazrul , Islam Rahib K , Rashid Mohammod B , Smith Branson , Islam Safa K
Published: October 2024

Disclosure: K.N. Islam: None. R.K. Islam: None. M.B. Rashid: None. B. Smith: None.

Diabetes is a leading cause of morbidity and mortality. Elevation of oxidative stress is a common cause in diabetic patients because of higher levels of blood sugar concentration. Nitric oxide (NO) is a gasotransmitter that has many health benefits for many disease conditions. NO also has an antioxidant property. The pancreatic β-cells are insulin-secreting cells. The present study was undertaken to investigate the effects of NaNO2, a donor of NO on glucose-induced oxidative stress in pancreatic β-cells (HIT) from a Chinese hamster. First, we determined the effects of dose responses of glucose (25, 50, 75, 100, and 150 mM) on the induction of oxidative stress as it was measured by the formation of thiobarbituric acid reactive substances (TBARS) in serum starved β-cells. We observed marked oxidative stress in the serum starved β-cells by the treatment with 75 mM of glucose. Later, we tested the effects of NaNO2 on glucose-induced oxidative stress in serum starved β-cells, and we found that NaNO2 markedly inhibited glucose-induced oxidative stress in serum starved β -cells. Treatment with NaNO2 caused significant induction of cell viability and a marked reduction of cellular cytotoxicity in β-cells under serum starvation incubated without or with glucose. In addition, NaNO2 treatment of β-cells antagonized expression levels of inflammatory cytokines, TNF-α and inhibited the activation of the transcription factor, NF-κB signaling pathway. Our findings suggest that NO or NO donors may be used as therapy to cure diabetes via inhibiting oxidative stress thereby decreasing blood sugar levels in diabetic patients.

Presentation: 6/3/2024
12521 Electrical Impedance Myography And Muscle Health In Older Adults With Type 1 Diabetes
Authors: Fremaint A , Jung G , Yu E , Bouxsein M
Published: October 2024

Disclosure: A. Fremaint: None. G. Jung: None. E. Yu: None. M. Bouxsein: None.

Introduction: Recent studies indicate that individuals with Type 1 diabetes mellitus (T1D) develop skeletal muscle health impairments which might contribute to falls and explain their high fracture risk. A novel handheld Electrical Impedance Myography (EIM) device (mScan model 1301, Myolex) has been developed to assess muscle quality by calculating tissue impedance. We hypothesized that mScan could identify individuals with worse strength and body composition outcomes among older adults with and without T1D. Methods: We studied participants of the T1D Bone Health Connection (BEACON) Study who were aged 50+ and who had undergone EIM testing (n=63 T1D, n=50 non-diabetic controls). We analyzed EIM-derived phase angle [Phase = arctan(reactance/resistance)] at 100 kHz in 3 upper extremity muscles (biceps brachii, lateral deltoid, and wrist extensors), where lower phase values indicate poorer muscle quality. Correlations of EIM data were performed with grip strength measured by a handheld dynamometer and appendicular lean mass/height2 (ALM/ht2) and visceral adipose tissue (VAT) from whole-body DXA scans. Pearson’s correlations were used for all statistical analyses. Results: Mean age (63±7 years), sex (54% female), and BMI (26.5 kg/m2) were similar between T1D and control groups. Adults with T1D had a nonsignificant trend towards lower muscle quality at the biceps brachii than controls (8.9±5.4 vs 10.9 ±6.0 degrees, p=0.078). There were no differences between groups in phase angle for lateral deltoid nor wrist extensors. Higher muscle quality at the biceps brachii was associated with higher grip strength (r=0.28, p=0.005) in the full cohort as well as in the T1D group (r=0.40, p <0.001). In the full cohort, greater VAT was associated with lower muscle health at the biceps brachii (r = -0.34, p=0.003) and lateral deltoid (r = -0.23, p<0.014), with similar patterns in both T1D and controls. There were no correlations of muscle quality with ALM/ht2. Conclusion: Our data suggest that mScan holds promise for detection of skeletal muscle health impairments in older adults, including those with T1D, potentially aiding in the diagnosis and prevention of related falls and fractures. Further research is required to investigate the association between VAT and muscle health and to validate the effectiveness of mScan in T1D and other populations.

Presentation: 6/3/2024
6920 Engagement and Mood assessments in Emerging Adults Attending a Multi-disciplinary Diabetes Transition Clinic
Authors: Thota G P , Glaros S , Dixon S , Chung S T
Published: October 2024

Disclosure: G.P. Thota: None. S. Glaros: None. S. Dixon: None. S.T. Chung: None.

Introduction & Objective: Transitioning to adult diabetes care can be challenging and associated with interruption in care, worsening glycemic control, and social stress. However, most studies have been conducted in emerging adults (YA) with type 1 diabetes (T1D), and contemporary data in multi-disciplinary clinics designed with supportive resources, especially for YA with youth-onset type 2 diabetes (Y2D) is lacking. Our objectives were to assess mood and engagement in psychology therapy services within a structured multidisciplinary diabetes clinic. Methods: This was a single-center observational analysis of YA (18-30y) attending a research diabetes transition clinic supported by clinical coordinators, social navigators, a certified diabetes educator, and a nutritionist between January 2021 and December 2023. All YA were offered free transportation to and from visits. Clinical coordinators communicated regularly for appointment reminders. Mood was assessed with Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder (GAD-7) at each visit and Endocrine Society Transition Readiness Form at initial visit. In January 2023, all YA were given the option to meet with a clinical psychologist during the diabetes visit. Student t-test were used to compare groups using STATA v.18. Results: In 62 YA (73% Y2D, 10% T1D, 17% other) aged 20.2±2.7y, BMI:37.3±9.6 kg/m2, all engaged in nutrition counseling and 52% (32/62) utilized transportation services. A diagnosed psychiatric disorder was present in 16% (10/62). At initial visit, PHQ-9 scores were 6.1±6.3, n=62 and39% (24/62) had score >8 (moderate depression). Within the last 2 weeks, 13% (10/62) reported suicidal ideation. GAD-7 scores were 6.0±6.3 and 54% had anxiety that interfered with activities of daily living. Psychology services were accepted in 61% (38/62) with higher initial GAD-7 scores in those who saw psychologist (8.2±6.8 vs. 4.1±5.3, P=0.02) but no difference in PHQ-9 scores (7.2±6.6 vs. 5.1±5.9, P=0.2). Most YA (81%) reported adequate diabetes knowledge while 25% YA reported diabetes-related challenges including feeling burned out, not knowing how to navigate specialty diabetes care, challenges with medication insurance, transportation, and insurance coverage. Conclusion: Approximately 50% of emerging adults with diabetes reported moderate depression and anxiety scores and were interested in engaging in psychology services. Transition diabetes care programs should focus on increasing access to routine integrated mental health services and social support.Such an initiative could potentially ameliorate psychological stressors associated with diabetes management during the transition to adult care.

Presentation: 6/1/2024
6538 Find me if you can! A Case of a "Well Placed Solitary Insulinoma" in "The Center" of an SACST
Authors: Kennedy Randol , D’Alessio David A , Vella Adrian V
Published: October 2024

Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None.

Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate < 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion.

Presentation: 6/1/2024