bluuebunny/crossref_metadata_2025 huggingface dataset:
12491 Follow Up Of Glycemic Control In Patients Users Of Sensor Augmented Insulin Pump (sap) After Multi Dairy Injection (mdi) Or Change Of Technology
Authors: Medina A , Tabares S , Coronado C , Burgos L , Ely A L
Published: October 2024

Disclosure: A. Medina: None. S. Tabares: None. C. Coronado: None. L. Burgos: None. A. Ely: None.

Introduction: Sensor augmented insulin pump (SAP) is considered an efective therapy in type 1 diabetes (T1D) that combines continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM). A new metric of glycemic control is the time in range (TIR). More time in the expected range means less severe highs and lows. Objective: To describe glycemic control of a cohort of patients treated with multi-daily injection (MDI) or sensor-augmented insulin pump (SAP) VEO /640G who switched to a new therapy with 640G, 670G and 780G at 3 and 6 months. Methodology: A cohort study was analyzed with patients with T1D receiving SAP therapy in an university hospital. Patients with insulin therapy with MDI or SAP (VEO /640G) prior to SAP (670G /780G) were included and were followed up with glycemic control trough A1c, time in range (TIR), time in hypoglycemia and hyperglycemia, glycemic variability (GV) using continuous glucose monitoring (CGM) for 14 days, at 3 and 6 months after starting a new technology. Results: 40 patients were analyzed from 2022 to 2023, who attended check-ups every 3 months. The median age was 32 y and 65% were male. At baseline data, 40%, 22.5%, 37.5% were on MDI, VEO and 640G respectively, before changing therapy to 670G or 780G. The TIR increased by 97.6% of the patients and 75% reached the TIR (>70% between 70 and 180 mg/dl of glucose).Hypoglycemia decreased in 75% of patients, and of 27 patients in hyperglycemia, only 3, did not decrease glucose levels due to: lack of follow-up, sensor failure and misuse of the pump. In this cohort were included 12 patients in special conditions. The average initial GV was 37,2%, the normal being <36%, with an improvement at 3 and 6 months of 32,8 and 32,9%, respectively.The mean basal A1c was 7,32% . A1c decreased to 6,8 and 6,9% at 3 and 6 months after new therapy. Discusion: Regardless of the basal therapy (MDI, SAP), an improvement in TIR and A1c as measures of glycemic control is observed, as well as a decrease in the time in hypo and hyperglycemia and GV. The few patients who did not experience improvement had poor pump management, inappropriate carbohydrate counting, or poor adherence at checkups. Conclusion: SAP is an effective therapy in patients with (T1D) to reach metabolic goals, without increasing the rate of hypoglycemia. The most recent technologies in insulin pumps demonstrate better glycemic control.

Presentation: 6/1/2024
6486 Gastroparesis Exacerbation by a GLP-1 Agonist
Authors: Deirmenjian Jacqueline M , Dagher Christopher
Published: October 2024

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

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<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<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<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

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

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 <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

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

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

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

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
6482 Knowledge and comfort in addressing eating disorders in people living with Type 1 Diabetes in an academic Endocrinology center
Authors: Viera Felicino Natalia , Lam David
Published: October 2024

Disclosure: N. Viera Felicino: None. D. Lam: None.

Background: Eating disorders(ED) occur at twice the rate in people living with type 1 diabetes(PWT1D) compared to the general population. Early detection and prevention necessitate a high level of clinical suspicion, as the coexistence of ED and T1D is linked to compromised metabolic control, earlier onset of microvascular complications, elevated mortality rates and diminished quality of life. Despite this, healthcare providers often encounter multiple challenges, such as the tendency for ED/DEB to be well hidden and/or denied, as well as a general discomfort in broaching this sensitive topic. Compounding the issue is the scarcity of literature offering optimal methods for supporting and treating individuals suffering from this dual diagnosis. Here, we conducted a survey at an academic center to assess providers’ overall knowledge and comfort level regarding the intersection of ED/DEB in PWT1D. Methods: A 15 question anonymous survey was distributed to members of our Endocrinology division, including fellows, attendings, and advanced practice providers (APPs) across four practices within an academic center in New York City. The primary objectives of the survey were to gauge participants' understanding in three key areas: general knowledge regarding the prevalence of this dual diagnosis, awareness of associated morbidity, and their professional experiences in providing care to this population. Results: The survey was distributed to a total of 40 participants with 29 responses: 38% Endocrine fellows, 41% attending physicians, and 21% APPs. 97% acknowledged that ED are more prevalent in PWT1D compared to the general population and 25% could identify validated screening tools for ED. Regarding the association between ED in PWT1D and health outcomes, 67% accurately identified the increased risk of developing microvascular complications and 36% recognized the increase in the risk of all-cause mortality. 71% reported caring for a PWT1D who expressed concerns about insulin and weight gain. When asked to rate their comfort level in addressing these concerns, 13.8% and 3.4% reported feeling comfortable and very comfortable, respectively. 86% of respondents expressed unfamiliarity with available resources for providing support to individuals in this group. Discussion: The results of the survey show general acknowledgment of the heightened prevalence of ED among PWT1D and association with morbidity and mortality, but emphasizes gaps in knowledge, a general sense of discomfort, and a shortage of resources to effectively manage individuals within this patient demographic. Our survey highlights the need for enhanced education and resources to better equip healthcare professionals in managing the complex intersection of both disorders. Given that diabetes outcomes are heavily dependent on behavioral adherence, strategies for addressing ED are crucial for comprehensive patient care.

Presentation: 6/2/2024
6491 Macrophage Depletion Does Not Affect Beta Cell Dedifferentiation in Islets of Prediabetic NOD Mice
Authors: Laybutt R , Chan J , Liang C , Lee K
Published: October 2024

Disclosure: R. Laybutt: None. J. Chan: None. C. Liang: None. K. Lee: None.

Background: Pancreatic beta cell dedifferentiation may be an important contributing factor to beta cell dysfunction in type 1 and type 2 diabetes, but the triggering stimuli are poorly understood. We previously demonstrated that islet macrophages are critically important for the disruption of beta cell identity gene expression in the db/db mouse model of type 2 diabetes. However, the effects of islet macrophages on beta cell identity in type 1 diabetes are not clear. Our goal was to examine the gene expression pattern of islet-associated macrophages in non-obese diabetic (NOD) mice and to assess their potential influence on beta cell identity and function. Methods: Islets were isolated from 12-week-old female prediabetic NOD mice and control BALB/c mice. Macrophages were sorted using flow cytometry. Islets were treated ex vivo with clodronate-containing liposomes to deplete macrophages. Gene expression was assessed by real-time RT-PCR. Insulin and proinsulin secretion was assessed. Results: Macrophages from NOD islets showed a distinct gene expression pattern compared to BALB/c islet macrophages, suggesting a different functional state. Macrophages from NOD islets displayed a less inflammatory gene expression pattern with reduced interleukin 1 beta (IL1b) and tumor necrosis factor alpha (Tnfα) and elevated IL-1 receptor antagonist (Il1rn). Islet cells from NOD mice displayed reduced expression of genes related to beta cell identity. The mRNA levels of islet-associated transcription factors (Pdx1, NeuroD1 and Nkx6.1), glucose transporter (Glut2), the rate-limiting enzyme of the glycerol-phosphate shuttle, mitochondrial glycerol phosphate dehydrogenase 2 (Gpd2), ATP-sensitive potassium channel (kcnj11), incretin GIP and GLP-1 receptors (Gipr and glp1r) and adaptive unfolded protein response genes (Xbp1, Hspa5, Grp94 and Fkbp11) were reduced. Clodronate-liposome treatment of islets depleted macrophages, as evidenced by reduced mRNA expression of CD11b and F4/80. However, the depletion of macrophages in islets of NOD mice did not affect beta cell identity gene expression. Beta cell dysfunction in NOD islets was evidenced by increased proinsulin secretion. Proinsulin secretion remained elevated following macrophage depletion in NOD islets. Conclusion: These novel findings suggest that islet macrophages of prediabetic NOD mice are in a reduced inflammatory state. In contrast to previous findings from our group in a mouse model of type 2 diabetes, we found that depleting macrophages in islets from NOD mice did not improve beta cell dedifferentiation. Depleting islet macrophages may not be beneficial for restoring beta cell identity gene expression in type 1 diabetes.

Presentation: 6/2/2024
9358 Maternal Blood Glucose And Hypothalamus Volume: Novel Insights For Intergenerational Transmission Of Endocrine Traits
Authors: Marchildon Cédrik , Arguin Mélina , Doyon Myriam , Cote Samantha , Michaud Andreanne , Huck Julia , Gingras Véronique , Perron Patrice , Hivert Marie-France , Bouchard Luigi , Whittingstall Kevin
Published: October 2024

Disclosure: C. Marchildon: None. M. Arguin: None. M. Doyon: None. S. Cote: None. A. Michaud: None. J. Huck: None. V. Gingras: None. P. Perron: None. M. Hivert: None. L. Bouchard: None. K. Whittingstall: None.

Objective: Several studies have linked maternal hyperglycaemia to diabetes-prone phenotype in the offspring, yet the mechanisms underlying these associations remain unclear. In adults, the hypothalamus is known to play a crucial role in the progression of obesity and diabetes. In utero exposure to maternal hyperglycaemia may thus selectively target the developing hypothalamus. To test this hypothesis, we explored the link between maternal glycemia and offspring brain volumes at 10-12-year-old. Methods: This study was conducted in a subgroup of 48 mother-child pairs from the Gen3G prospective pre-birth cohort. Pregnant women completed a 75g oral glucose tolerance test (OGTT) at 24-30 weeks of pregnancy. Maternal glucose was measured at fasting, 1h, and 2h during the OGTT and area-under-the curve of glucose (AUCgluc) was calculated using the trapezoid method. When participating offspring reached 12 years of age, they were invited back to the clinical research centre to complete a high-resolution structural MRI from which regional brain volumes and hypothalamic subvolumes were quantified using FreeSurfer (Fisch, 2012). Results: Participating mothers were 28.6 (± 4.4) years old at enrolment, their mean BMI was 25.3 (± 6.3) kg/m2, and 6 women had gestational diabetes diagnosed from the IADPSG criteria. At follow-up, offspring were 10.9 (± 0.4) years old, and mean BMI was 18.3 (± 3.3) kg/m2. Our investigation revealed a significant and positive correlation between maternal AUCgluc and total offspring hypothalamic volume (r = 0.41, p = 0.004, n = 48). No significant correlations were observed in other cortical and sub-cortical regions (all p>=0.05). The link between maternal AUCgluc and hypothalamic volume was considerably stronger in female offspring (r = 0.54, p = 0.008, n = 23) than in males (r = 0.26, p = 0.22, n = 25). Conclusions: We found an association between higher maternal glycemia and greater offspring hypothalamic volumes, particularly among females. These results suggest that prenatal exposure to hyperglycaemia may lead to hypothalamic programming in a sex-dependent manner. Considering that recent studies have linked the hypothalamic disturbances to endocrine dysregulation, our findings may lead to a new understanding of obesity and the intergenerational transmission of endocrine traits. Ref:Fischl B. Freesurfer. NeuroImage. 2012 Aug 10;62(2): 774-81. doi:10.1016/j.neuroimage.2012.01.021

Presentation: 6/2/2024
7393 Measuring Diabetes Outcomes of Telemedicine Versus In-Office Visits at an Endocrinology Practice in Rural West Virginia
Authors: Muojieje Chukwudi , Driscoll Henry Keane , Thiab Ghadah , Nayiri Derian , crow Samuel , Saurborn Emily , Boustany Heba
Published: October 2024

Disclosure: C. Muojieje: None. H.K. Driscoll: None.

Background: West Virginia has limited specialty access despite high diabetes rates. Telemedicine expanded during COVID-19 as an alternative for care delivery while encouraging social distancing. Objective: Compare diabetes outcomes between telemedicine and in-office visits at the Marshall Health Endocrinology practice in Huntington, West Virginia Methods: Retrospective cohort study using records from Marshall Health Endocrinology from March 2019-March 2023. Adults aged 18-65 with type 1/type 2 diabetes with baseline HbA1c >7% on medications were included with clinic follow-up every 6 months. Primary outcome was HbA1c change. Secondary outcomes were changes in LDL cholesterol, triglycerides, microalbumin/creatinine ratio and diabetes hospitalizations. Change scores were calculated by subtracting values from the visit from values at 3-6 month follow up. Wilcoxon Signed Rank test compared outcomes within each patient. The study was approved by the Marshall IRB. Results: Of 72 patients, 8 had complete data allowing comparison between visit types for HbA1c. HbA1c increased after telemedicine (mean=-1.2; SD=2.08) but stayed the same after in-office (mean=0.03; SD= 0.19; p=0.039). Insufficient data precluded analysis of secondary outcomes. Conclusion: Results suggest potentially worse glycemic control with telemedicine versus in-office visits, unlike prior studies finding equivalence between telemedicine and in-office care for diabetes outcomes. This study’s findings were similar to previous study that have found telemedicine had slightly worse outcomes. This contrasts with other previous studies that generally found telemedicine to be equally efficacious for diabetes management. The small sample size precludes definitively establishing worse outcomes for telemedicine. Larger randomized studies are needed to definitively compare outcomes between visit types for rural diabetes populations and determine if telemedicine truly delivers subpar diabetes outcomes compared to in-office care.

Presentation: 6/3/2024
5036 Metformin-associated vitamin B12 deficiency as a potential cause of recurrent chronic subdural hematoma
Authors: Thewjitcharoen Yotsapon , Chongvoranond Peachaphol , Nakasatien Soontaree , Krittiyawong Sirinate , Himathongkam Thep
Published: October 2024

Disclosure: Y. Thewjitcharoen: None. P. Chongvoranond: None. S. Nakasatien: None. S. Krittiyawong: None. T. Himathongkam: None.

Background: Metformin-associated vitamin B12 deficiency is now considered a common side effect especially in those receiving a higher dose and those with existing risk factors. Many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed especially in patients with non-classical manifestations such as mild anemia without macrocytosis, neuropsychiatric manifestations, and symptoms of frailty. Among elderly individuals, the spectrum of symptoms and signs suggestive of vitamin B12 deficiency might be nonspecific and may occur because of other diseases. Due to the aging population, the incidence of chronic subdural hematoma has been on the rise. Here, we present a case of metformin-associated vitamin B12 deficiency as a potential underlying cause of gait instability leading to a recurrent chronic subdural hematoma. Clinical case: An 84-year-old man with well-controlled type 2 diabetes mellitus presented to the outpatient department with dizziness and fatigue for 2 weeks. The patient did not report any recent trauma. He had been in his usual state of health until 10 months ago when he began to have frequent fallings and fatigue. Acute-on-chronic subdural hematoma was found from computed tomography of the head. The patient’s history was significant for type 2 diabetes mellitus with metformin treatment 1,700 mg/day for more than 25 years, post-transcatheter aortic valve implantation for aortic stenosis, and coronary artery disease. He had been on dual antiplatelet therapy and proton pump inhibitor. Subsequent evaluations demonstrated mild normocytic anemia, mild thrombocytopenia, undetectable plasma vitamin B12 level, elevated plasma homocysteine, and normal folate level. Improvement in neurological symptoms occurred within one week of vitamin B12 replacement and surgical hematoma evacuation. Conclusions: Our case highlights the importance of assessing vitamin B12 status among elderly patients taking metformin and it is essential for clinicians to maintain a high index of suspicion in elderly patients with prolonged use of metformin presented with gait instability and frequent fallings. With the ageing of society and the continuing growth of the older population, metformin-associated vitamin B12 deficiency is expected to have an emerging complication in the future. Routine measurement of vitamin B12 level for metformin-treated individuals should be considered.

Presentation: 6/1/2024
6909 Mortality and Readmission Rates for Inpatients with Diabetic Foot Ulcer in a Tertiary, Urban Medical Center: A Five-Year Retrospective Review
Authors: Chancay Azucena Herrera , Fanas Raul Lopez , Tabassum Humera , Daily Johanna , Myers Alyson
Published: October 2024

Disclosure: A. Herrera Chancay: None. R. Lopez Fanas: None. H. Tabassum: None. J. Daily: None. A. Myers: None.

Background: Diabetic Foot Ulcer (DFU) is a severe complication of diabetes mellitus and is associated with high rates of morbidity and mortality. The incidence of DFUs and amputation disproportionately impact Black and Hispanic populations. DFU is also associated with a high rate of hospital readmissions and prolonged length of stay (LOS). The goal of this study was to examine 1-year mortality data, LOS and readmission rate. Methods: This study was a retrospective chart review of 1348 patients admitted to three hospitals in our system in the Bronx from 6/1/16 to 5/31/21. Data was extracted from the EPIC® electronic health records, based on the diagnoses ICD 10 codes, E10.621 and E11.622. Inclusion criteria was patients admitted with an active DFU regardless of other admission diagnosis, age 18 years or above. The index admission was defined as the first admission in our medical records within the date range. Patients were excluded if their index admission was not accessible through our EMR. Simple logistic regression and multiple logistic regression were used to analyze the association between variables of interest and mortality at index admission and at 1-year, LOS and re admissions. Results: Of the 650 eligible patients, the mean age was 59 + 13 years, 70% of patients were male, and majority were non-White (88%). Mortality was 1% during the index admission and the risk increased to 6% at 1 year after the index admission. Readmission with an active DFU from the index admission occurred in 15% of patients within 30-days, 32% of patients within 90 days, and 55% of patients within 1 year. The mean length of stay was 9 +7.5 days. Discussion: Our study in an urban region has identified high rates of mortality and costs associated with DFU, which has been reported in many settings. This patient population is high risk for poor outcomes and targeted programs are needed to reduce mortality and provide care to reduce readmissions. Future studies that explore the challenges of DFU health care and that test interventions are needed to improve DFU related health outcomes.

Presentation: 6/2/2024
12328 Multimodal Imaging Reveals Changes In Beta Cell Metabolism And Heterogeneity Throughout Pregnancy
Authors: Cuala Janielle M , Singh Tvisha , Deng Chris , Jayapalan Kavya , Dhawan Sangeeta , White Kate , Georgia Senta
Published: October 2024

Disclosure: J.M. Cuala: None. T. Singh: None. C. Deng: None. K. Jayapalan: None. S. Dhawan: None. K. White: None. S. Georgia: None.

During pregnancy, a unique, transient metabolic stressor, pancreatic islets adapt by balancing hormone production to maintain tight glucose homeostasis. Maternal insulin demand increases as systemic insulin resistance increases. To keep up with the increase in demand, beta cell functional dynamics change throughout pregnancy, including increasing insulin synthesis and lowering the threshold for glucose-stimulated insulin secretion (GSIS). Failure to adapt can lead to gestational diabetes (GD), a complication in 14% of pregnancies worldwide, feeding into a vicious cycle of impaired function and, eventually, hyperglycemia. Fundamentally, beta cell function is dictated by its metabolism, calcium signaling, and insulin content upon glucose stimulation. To better understand how beta cell maladaptation during pregnancy leads to gestational diabetes, we propose to apply a multidisciplinary approach to integrate novel tools to assess function and metabolism fluctuations throughout normal pregnancy. Using live isolated islets from wild-type C57BL/6 (BL6) and InsCre-gCAMP6f fl/fl (INS-gCAMP) mice, we will measure GSIS and take 4D images using metabolic fluorescence lifetime imaging (FLIM) and confocal microscopy to visualize and quantify metabolic and functional changes at different time points at cellular resolution. We expect functional and metabolic capacity levels to increase during the onset of beta cell remodeling (∼Day 8) and continue to peak throughout pregnancy. In contrast, changes in beta cell heterogeneity become more evident at the peaks of beta cell proliferation and expansion (∼Day 11-14). The proposed study will implement novel techniques to establish beta cell functional and metabolic information within a 3D pancreatic islet context throughout different time points of pregnancy. With this, we will provide greater insight into beta cell biology and its adaptation to metabolic stress to better understand the progression of gestational diabetes, which can then be applied to investigate other cellular adaptive dynamics that affect health and disease.

Presentation: 6/2/2024
7636 Once-weekly Insulin Icodec versus Once-daily Long-acting Insulins for Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Authors: Ribeiro S G , Chavez M P , Hespanhol L C , Neto A B , Gauza M d , Paqualotto E , Balieiro C A , Padovese C C , Sa J R
Published: October 2024

Disclosure: S.G. Ribeiro: None. M.P. Chavez: None. L.C. Hespanhol: None. A.B. Neto: None. M.D. Gauza: None. E. Paqualotto: None. C.A. Balieiro: None. C.C. Padovese: None. J.R. Sa: None.

Background: Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. Objective: Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using weighted mean differences (WMDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). Results: A total of seven RCTs and 3,286 patients with T2DM were included, of whom 1,509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (WMD -0.15%; 95% CI -0.21, -0.10; p<0.0001; I²=0%) and time in range (TIR) (WMD 2.83%; 95%CI 0.94; 4.71; p=0.003; I2=22%). Body weight was increased with icodec treatment (WMD 0.78 Kg; 95%CI 0.42, 1.15; p<0.01; I2=86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p=0.016; I²=0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p=0.020; I²=0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. Conclusions: In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.

Presentation: 6/3/2024