Diabetic Ketoacidosis Research Articles

6844 Comparison of Lactated Ringers and Normal Saline in the Treatment of Diabetic Ketoacidosis

Abstract 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

9332 Breathless Struggle: Unraveling The Interplay Between DKA And Acute Respiratory Distress Syndrome

Abstract 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

12397 Predictors Of Hospital Readmission Within Three Months Among Patients Admitted For Diabetic Ketoacidosis (dka)

Abstract Disclosure: O. Onwudiwe: None. L. Yerashevich: None. C. Onwudiwe: None. B. Baral: None. A. Acharya: None. H. Nguyen: None. Purpose: Diabetic ketoacidosis (DKA) represents a critical, life-threatening complication of diabetes, with higher rates of re-admission noted among individuals from lower socioeconomic backgrounds, those lacking insurance coverage, and those with suboptimal follow-up care. This study seeks to identify predictors of hospital readmission within three months among patients admitted for DKA in a community hospital setting. Methods: Patient data were extracted from electronic medical records from 2019 to 2021 for individuals admitted due to DKA using ICD codes. DKA diagnosis was based on the presence of hyperglycemia, high anion gap metabolic acidosis, and ketonemia. Demographic information, results of routine biochemical tests, insurance status, follow-up with primary care providers (PCP) or endocrinologists, and clinical progression were retrospectively collected from patients' records. Multivariable logistic regression analyses were conducted to identify predictors of readmission. Results: A total of 222 unique DKA admission visits were analyzed. The mean age (standard deviation) of the patients was 48 (16) years, and 58% of them were male. Among these visits, 39% had type 1 diabetes, 43% had type 2 diabetes, and 18% were newly diagnosed diabetes cases. The majority of patients were overweight, with a mean body mass index (BMI) of 27, and the mean glycated hemoglobin level was 10.8. Common triggers for DKA included insulin non-adherence (52%), infection (37.8%), and alcohol use (8.6%). Logistic regression analysis revealed that lack of follow-up significantly increased the odds of readmission within three months (B = 2.025, p = .003, Exp(B) = 7.576, 95% CI [1.952, 29.401]), as did having type 1 diabetes (B = 1.473, p = .019, Exp(B) = 4.364, 95% CI [1.272, 14.978]). However, the association between insulin adherence and readmission was not statistically significant at the conventional alpha level of 0.05 (B = 1.329, p = .112, Exp(B) = 3.777, 95% CI [0.733, 19.458]). Other demographic (age, gender, employment status, insurance status, medication compliance,) and clinical [insulin adherence, presence of infection, blood glucose level at diagnosis of DKA, and level of glycated hemoglobin (Hba1c)] variables did not significantly predict readmission within 3 months. Conclusion: DKA, being preventable with adequate insulin adherence, is also influenced by factors such as infection and lifestyle choices. The findings highlight the critical role of post-discharge follow-up care in reducing readmission rates among DKA patients. Healthcare providers should prioritize ensuring timely and comprehensive follow-up, particularly for patients with type 1 diabetes, to optimize post-hospitalization management and prevent avoidable readmissions. Presentation: 6/3/2024

7531 Spontaneous Coronary Artery Dissection Induced Diabetic Ketoacidosis In A Young Female: A Rare Complication Of Ketosis In A Priorly Non-Insulin Dependent Diabetic

Abstract Disclosure: F. farhat: None. P. Gonzalez: None. A.B. Ravin: None. H. Akhlaq: None. M. hossain: None. K. chalasani: None. S.W. Holland: None. R. Ong: None. J. Cheng: None. Introduction: Spontaneous Coronary Artery Dissection (SCAD) is a poorly understood and underdiagnosed condition that puts healthy young women at risk of Myocardial infarction (MI) and potential death. It occurs when a tear develops in a coronary artery. SCAD can have an atypical presentation especially in diabetic and young females; Diabetic ketoacidosis (DKA) is an uncommon, yet potentially fatal complication and can be the primary presentation in SCAD. We present a case of SCAD complicated by DKA in a non insulin dependent diabetic (NIDD).Case presentation: A 19 year old female with a past medical history of NIDDM presented to the Emergency Department with chest pain. She had troponemia and ECG revealed ST elevations. Patient was found in DKA initially. Insulin drip was started with DKA resolution in 24 hours. Hemoglobin A1c was 12.4% with negative antibody workup. Her course was complicated by SCAD found upon cardiac catheterization with unsuccessful recanalization; she was not a surgical candidate given late presentation and therefore, an intra aortic balloon pump was placed. Subsequently, she developed pericarditis and left ventricular thrombus. Discussion: SCAD is a rare condition, often presenting with acute MI and cardiogenic shock. MI may be complicated with DKA. One proposed mechanism for that is the activation of ketogenic pathways caused by excess catecholamines and cortisol; this increases physiologic stress on the body resulting in increased ketogenesis, lipolysis and free radicals causing further myocardial injury. DKA precipitated by MI increases the mortality rate to nearly 85% since the myocardium is denied glucose uptake. Signs and symptoms of SCAD are similar to MI symptoms including: chest tightness, shortness of breath and sweating. MI and SCAD can be differentiated by cardiac catheterization or by specialized contrasted CT scans. 20% of SCAD patients will experience a second episode within 5 years. Avoiding emotional stress, exercising regularly, following a healthy diet and controlling chronic conditions can help lower the risk for SCAD. Medical management is often preferred. Invasive treatments like coronary stenting or cardiac bypass may be needed if there is a complete blockage in the vessel, clinical instability or ongoing chest pain. Conclusion: SCAD is an important cause of MI in young females and can present initially as DKA in diabetics. For clinicians facing such rare cases, it is worth maintaining a broad approach to the diagnosis and treatment of these patients. The causes of SCAD remain fully unclear and genetic relations are still under investigation. Since DM type I and SCAD occur in young people, it is extremely important for clinicians to consider SCAD in the differential while managing DKA. Presentation: 6/3/2024

12469 Impact Of Covid-19 Infection On Diabetic Ketoacidosis Severity And Outcomes In Adult Population- A Retrospective Observational Study

Abstract Disclosure: E.M. Niedzialkowska: None. K. Childers: None. L. Qu: None. L. Misra: None. M.R. Brennan: Consulting Fee; Self; Insulet Corporation, Bayer, Inc., Novo Nordisk. Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM) that can be precipitated by SARS-CoV2 infection. We analyzed clinical and demographic characteristics of patients admitted with DKA to investigate if SARS-CoV2 infection affects DKA severity on admission and outcomes. Methods: We conducted a retrospective cohort study that included adult patients admitted with a diagnosis of DKA between March 1, 2020, and March 1, 2023. Patients' demographic data including age, sex, race, ethnicity, laboratory test results on admission, ICU admissions and length of hospital stay (LOS) were compared. Patient characteristics and outcomes of interest were stratified by COVID-19 test results and compared using the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. DKA severity was classified based on HCO3 values: mild 15-18 mEq/L, moderate 10-14 mEq/L, severe <10 mEq/L. Results: The study included 902 patients, of which 734 tested negative (COVID-) and 168 tested positive (COVID+) for SARS-CoV2. The mean age was significantly higher (54.09) in COVID-19+ group compared to COVID-19- group (48.25) (p<0.001). The cohort included 49.1% females, 51.7% Whites, 43.3% Blacks, 89.8% Non-Hispanic/Latino, 2.7% Hispanic/Latino. We did not find statistically significant differences in sex (p= 0.608), race (p =0.277), ethnicity (p=0.072) anion gap (p=0.783), glucose (p=0.140), hemoglobin a1c (ha1c) values on admission (p=0.876) and ICU admissions (p=0.266) between both groups. The majority (55.3%) of the patients presented with severe DKA, followed by moderate DKA in 26.6% and mild disease in 18.1% of patients without statistically significant differences between groups (p= 0.128). The mean LOS in COVID + group (11.94 days) was longer than COVID- (6.85) group (p<0.001). Mean venous pH was significantly lower in COVID-19- (7.14) compared to COVID+ (7.17) group (p= 0.016). Betahydroxybutyrate (BHB) levels on admission were higher in COVID- group (7.98 mmol/L, N 0.02-0.27 mmol/L) compared to COVID + (7.10mmol/L) cohort. Conclusion: Patients diagnosed with COVID-19 and DKA on admission did not present with more severe disease compared to patients that tested negative. COVID+ patients were older (54.09 vs 48.2) and had significantly longer LOS (11.94 vs 6.85 days). We did not identify statistically significant differences between race, ethnicity, sex, glucose, anion gap, Ha1c on admission and ICU admission rate. BHB levels on admission were higher in patients that tested negative. Interestingly, mean pH was higher in COVID-19 positive group possibly due to respiratory disorders. Presentation: 6/1/2024

7241 Catamenial Diabetic Ketoacidosis

Abstract Disclosure: L. Javed: None. A. Rehan: None. L. Hashim: None. J. Lim: None. Introduction: Diabetic ketoacidosis (DKA) is a common cause of hospitalization and readmission in patients with diabetes mellitus. Etiologies are generally due to medication non-adherence, trauma, infection, or other precipitating illness. In approximately 10% of DKA cases, no discernible precipitating cause can be determined. The word catamenial is derived from a Greek word meaning monthly. It is used to describe the monthly occurrence of menstruation. Catamenial hyperglycemia is a phenomenon in which blood glucose levels change with the different phases in the menstrual cycle. This can precipitate recurrent, unexplained episodes of DKA. Here, we present a similar case. Case description:A 19-year-old woman with type 1 diabetes, gastroparesis, hypertension, dysmenorrhea and cyclical vomiting disorder presented with unrelenting nausea and vomiting for one day. Other symptoms included abdominal & chest pain that the patient attributed to premenstrual symptoms. She is afebrile, doesn’t have any other symptoms of infection and no recent sick contacts. She is compliant with her home insulin regimen of Insulin detemir 20 units BID and pre meal 8 units insulin aspart. Further interrogation reveals she has regular menstrual cycles and has been hospitalized three times in the last three months due to DKA coinciding with premenstrual symptoms, specifically severe abdominal pain and vomiting, typically starting five days before the onset of her menstrual cycle. She is hemodynamically stable and physical exam is significant for mid epigastric tenderness. Significant labs: WBC 16.52 (N<11 K/mm3), glucose 457 mg/dl, anion gap 23, K 4.1 (mmol/L), bicarbonate 18 (≥19 mmol/L), lactate 3.2 (N ≤ 1.9 mmol/L), beta hydroxybutyarate 4.0 (N ≤ 0.27 mmol/L), trop T 6 (N<10 ng/L), BHCG negative . Hba1c a month ago was 9.6%. Infectious work up was negative. EKG showed no signs of ischemia. She was treated per DKA protocol which results in resolution of symptoms and normalization of labs. Since no other precipitating factors for DKA are identified, and her symptoms corresponded with her menstrual periods, she is given a diagnosis of Catamenial DKA and scheduled for regular follow up in endocrinology clinic. Conclusion: This case highlights the importance of considering the association betweenmenstrual cycle phases and blood sugar levels as a possible trigger, underscoring the role of a thorough menstrual history in patients presenting with DKA. The impact of menstrual cycle fluctuations on glycemic control varies among patients however glucose profiles seem to be consistent across cycles for each individual woman. This highlights the need for personalized management strategies including patient education and adjustment of insulin during these periods. Addressing this adequately will improve overall glycemic control, reduce hospitalizations, and help improve the quality of life. Presentation: 6/1/2024

7555 Gender-Related Differences in Outcomes of Patients With Diabetic Ketoacidosis: An Analysis of the National Readmission Database

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

8725 Subcutaneous Compared With Intravenous Insulin Protocol For Management Of DKA: A Longitudinal Experience In A Single Center

Abstract Disclosure: S. Avula: None. M. Salim: None. E. Wetherbee: None. C. Wenner: None. A. Gravely: None. A.D. Westanmo: None. N.G. Ercan-Fang: None. Background: Diabetic ketoacidosis (DKA) is a critical condition requiring immediate medical attention to prevent severe health complications and even death. Typically, patients are placed under the care of the intensive care unit (ICU) to ensure close supervision. With implementation of effective subcutaneous insulin protocol (SIP), patients can be safely managed outside of ICU without any significant change in mortality or morbidity, potentially decreasing financial burden of costly ICU stay. Aim: To review and compare the experience with subcutaneous and intravenous insulin protocols for management of DKA at Minneapolis Veterans Affairs Health Care System (MVAHCS). Methods: We conducted a retrospective chart review of patients who were admitted with DKA at MVAHCS from 2013 - 2023 and were treated with either I.V insulin or SIP. Inclusion criteria: Adults (age >/=18 years) admitted with DKA between 2013 and 2023. Exclusion criteria: Non availability of VBG/ABG and patients who were not treated initially at MVAHCS. Statistical analysis used was basic descriptive analysis, Pearson’s Chi-Square and Two sample T test. Results: Majority of patients included were males: 57 (96.61%) and 16 (88.89) in SIP and I.V insulin, respectively. Racial distribution of patients was skewed towards a white population: Total of 57 (74.03%) were white, 12 (15.58%) were African American (AA). A significant majority of white patients 47 (79.66%) were on SIP, while 10 (55.56%) were on I.V insulin. Mean age of SIP and I.V insulin study populations were 58.9 (SD 16.21) and 59.2 years (SD 12.23), respectively. Baseline mean pH of the SIP and I.V insulin study populations were 7.27 (SD 0.08) and 7.13 (0.13), respectively. Mean bicarb for SIP was 14.9 mEq/L (SD 4.60) and I.V Insulin was 10.1 mEq/L ( SD 4.57). Mean time for anion gap (AG) closure among patients on SIP was modestly higher at 19.7 hours (SD 15.3) when compared to that on I.V insulin of 17.1 hours (SD 12.4) but the difference did not reach statistical significance. Similarly, 55.6% (n=10) of patients on I.V insulin and 58.6% (n=34) of those on SIP had anion gap closure of >/= 12 hours (p = 0.8187). When adjusted for baseline pH and bicarbonate, 46% of patients in the I.V insulin group had AG closure >=12 hours, whereas 67% of those in the SIP group had AG closure >=12 hours with total difference of 21% (p= 0.2098). Conclusion: Our results demonstrate that SIP can be safely implemented outside of the ICU setting. Compared with SIP, baseline pH was slightly less in the IV group (our protocol directs sicker patients with lower baseline pH towards the I.V insulin rather than SIP), however, AG closure time was similar between the two groups even after performing multiple regression analysis where we adjusted for baseline differences between two treatment groups in pH, bicarbonate, AG. These results indicate that SIP could be safe and potentially cost saving alternative for DKA management. Presentation: 6/3/2024

12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus

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

8494 A Case of Diabetic Ketoacidosis in Setting of COVID-19 Infection and SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. S. Bajpay: None. A. Abrahimi: None. Background: COVID-19 infection can cause endocrine system disruptions leading to the development of diabetic ketoacidosis (DKA) in patients with type 1, 2 or new onset diabetes mellitus. (1) DKA is a side effect of SGLT-2 inhibitor use and its development on the medication can lead to discontinuation of SGLT-2 inhibitor. (2) SGLT-2 inhibitors are part of guideline directed medical therapy for management of heart failure with reduced ejection fraction (HFrEF). (3) Case: 67-year-old female history of non-insulin dependent diabetes mellitus type 2 on Empagliflozin presented with shortness of breath and hypoxia. Initial BMP: Glucose 141 mg/dL, bicarb 24 mmol/L, anion gap of 10 mmol/L. Patient test positive for COVID-19 and was admitted for acute hypoxic respiratory failure in setting of COVID-19 infection. Six hours after patient received first dose of dexamethasone, labs showed BMP: Glucose 582 mg/dL, bicarb 14 mmol/L, anion gap of 20 mmol/L. ABG: pH 7.09, bicarb 13.2 mmol/L, glucose 509 mg/dL, lactate 9.6, beta-hydroxybutyrate 1.15 mmol/L. Patient was diagnosed and treated for DKA. Patient had an echocardiogram which showed new HFrEF. There was initial hesitation to restart patient on home Empagliflozin due to recent development of DKA. Literature review showed cases of DKA associated with COVID-19 infection. Etiology of DKA remained unclear. Ultimately, it was decided to restart patient on home Empagliflozin for management of diabetes and HFrEF. Conclusion: An abundance of evidence support the benefits of SGLT-2 inhibitors for patients with and without type 2 diabetes mellitus. (4) It is important to consider other causes of DKA for patients who develop DKA on SGLT-2 Inhibitors. Furthermore, additional research into endocrinopathies related to COVID-19 infections should be considered.

12621 Convergence Of Sglt2 Inhibitors And Glp1 Agonists: Unveiling The Recipe For Euglycemic Diabetic Ketoacidosis

Abstract Disclosure: U. Syed: None. N.E. Fretes Oviedo: None. V. Variar: None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a known adverse effect associated with the use of SGLT2 inhibitors. The concomitant initiation of GLP1 agonists with SGLT2 inhibitors presents a potential synergistic risk, precipitating metabolic acidosis without significant hyperglycemia. The individual propensity of both medication classes to contribute to metabolic disturbances highlights the necessity for heightened clinical awareness. Clinical Case: We present a case of a 34-year-old female with morbid obesity and Type 2 diabetes mellitus, receiving tirzepatide, metformin, and empagliflozin. The patient was initiated on empagliflozin 4 days prior, and tirzepatide one day prior to presentation. Shortly after commencing tirzepatide, she experienced symptoms of decreased appetite, abdominal pain, and vomiting. Workup was consistent with DKA with blood glucose < 250 mg/dL. Management involved strict adherence to DKA protocols. The patient’s symptoms resolved with resolution of ketoacidosis. Conclusion: Euglycemic DKA poses a diagnostic challenge for patients on SGLT2 inhibitors. Concurrent administration of GLP1 agonists, while not directly implicated, may exacerbate this condition, by their gastrointestinal side effects and resultant metabolic abnormalities. Awareness of potential interactions and associated risk factors is crucial for timely diagnosis and management. Presentation: 6/3/2024

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

7277 Diabetic Ketoacidosis As The First Manifestation Of Ectopic Cushing’s Syndrome

Abstract Disclosure: R.S. Medeiros: None. Introduction: Ectopic Cushing’s Syndrome (ECS) represents 10-20% of all ACTH-dependent CS, and the majority of cases arise from lung carcinoids. These indolent lesions usually evolve clinically over 6-24 months, whereas carcinomas are associated with faster onset of ECS. Diabetic Ketoacidosis (DKA) as a presenting manifestation of Cushing’s Syndrome (CS) is very rare, with the few cases published to date related to Cushing’s disease. Clinical Case: A 42-year-old woman was admitted in the emergency room with DKA and COVID-19. During stabilization, florid CS was clinically suspected. She reported a 6-month history of secondary amenorrhea, lack of concentration and memory, easy bruising, proximal myopathy with frequent falls evolving to daily life dependency from relatives. She also reported a 2-month diagnosis of dyslipidemia, Diabetes and hypertension, and a diagnosis of atypical pneumonia 6 months ago. Physical exam showed typical cushingoid appearance, especially for marked limb sarcopenia and proximal myopathy. An overnight dexamethasone suppression test (morning cortisol: 25.7 ug/dL), 24h urinary free cortisol (UFC; 1072.5 ug/dL; reference: <176) and serum cortisol at 23h00 (25.5 ug/dL) confirmed CS. ACTH-dependent CS was diagnosed. She had non-suppressible serum cortisol in high dose dexamethasone suppression test, and CRH stimulation test was suggestive of Cushing’s disease only by a 20% rise of cortisol at 30 minutes. Pituitary MRI was normal. Inferior Petrosal Sinus sampling was postponed for several months due to healthcare strikes. The patient started 750 mg of metyrapone in three divided doses but rapidly decreased the dose and stopped it due to clinical resolution of CS, a dramatic improvement of all glucocorticoid-related comorbidities leading to discontinuation of statin, insulin, main oral anti-hyperglycemic and antihypertensive medications, and normal midnight salivary cortisol and 24h UFC. She remained in this eucortisolemic state for 12 months. Thoracic CT scan revealed thymic hyperplasia and a 25x15 mm well-defined nodule in the lingula. A 68Ga-DOTANOC PET/CT showed a single uptake in the same lung region. The patient underwent lingulectomy plus excisional biopsy of interlobar lymph nodes, and pathology revealed a low-grade neuroendocrine tumor (Ki67<2%, <2 mitosis) without involved lymph nodes. The patient is weaning off from physiologic doses of hydrocortisone. Conclusion: DKA can rarely be the presenting manifestation of severe CS, including ECS. Clinicians should suspect on this etiology of DKA based on clinical signs and cumulative morbidity not typical of a young patient. This hint would lead to the expedite implementation of targeted therapies for initial stabilization of the CS patient, and the timely institution of a proper diagnostic approach and definitive treatment of this challenging patients. Presentation: 6/2/2024

7672 Ketosis-Prone Diabetes - A Case Series

Abstract Disclosure: T. Ismail: None. A. Farooq: None. G. Acharya: None. J. Snitzer: None. Introduction Ketosis-prone diabetes (KPD) is a syndrome that primarily affects African Americans. It is characterized by ketoacidosis, which is like Type 1 Diabetes Mellitus (T1DM). KPD is unique because it lacks identifiable autoimmunity and has a relative insulin deficiency, resembling Type 2 Diabetes Mellitus (T2DM). Therefore, KPD is informally classified as Type 1.5 Diabetes Mellitus. However, the clinical course and outcomes of KPD are like those of T2DM, and managing blood sugar levels is possible through non-insulin antidiabetic medications and dietary interventions. Case Series: Our study involved six patients who were all of African-American ethnicity. There were an equal number of male and female patients, with ages ranging from 21 to 61 years. One patient had a BMI of 27.2, which is considered overweight, while the rest had a BMI in the obese category ory(BMI>30). Two out of six patients had a pre-existing diagnosis of type 2 diabetes mellitus (T2DM) before the initial diabetic ketoacidosis (DKA) event. One patient had prediabetes. All patients required hospitalization for ketoacidosis and hyperglycemia and were found to have a glycated hemoglobin (HbA1c) level of more than 10% during these DKA events. All patients received intravenous hydration and insulin drip treatment and were discharged with a combination of long and rapid-acting insulin regimens. Following the resolution of the first episode of diabetic ketoacidosis (DKA), all six patients experienced a decrease in their insulin requirements for optimal glycemic control. Currently, four patients have discontinued insulin entirely. Moreover, all six patients tested negative for the presence of GAD-65, insulin, and islet antigen-2 antibodies. Among the patients, only one had a previously established autoimmune disease, i.e., inflammatory bowel disease. None of the patients experienced a repeat episode of diabetic ketoacidosis. Conclusion: It is important to note that not all patients who present with Diabetic ketoacidosis have Type 1 Diabetes Mellitus (T1DM). Hence, checking auto-antibodies for T1DM before making a final diagnosis is crucial. C-peptide levels may not accurately reflect the degree of relative permanent insulin deficiency in this population if measured during or immediately after an episode of diabetic ketoacidosis due to glucose toxicity and other factors. Given its prevalence in obese individuals, weight loss through dietary modifications and GLP-1 receptor analogs may be beneficial. Presentation: 6/3/2024

8177 Clinical Characteristics of Ketosis Prone Diabetes: Evaluating Diagnosis and Management Practices in a Real-Life Setting

Abstract Disclosure: Z. Tariq: None. A. Sinha: None. G. Shokry: None. K. Moors: None. S.S. Kodukula: None. Z.I. Saeed: None. Aims: While evidence supports the Aß (Auto-antibody status, Beta-cell function) classification of Ketosis Prone Diabetes (KPD), its implementation by healthcare providers (HCPs) remains unclear. We examined practices in managing KPD in a tertiary-care center and compared features between Aß subgroups. Methods: A retrospective longitudinal cohort study was conducted consisting of individuals aged 18 and above with diabetes who experienced diabetic ketoacidosis (DKA) between 2016 and 2021. Demographics, causes of DKA, auto-antibody status, beta-cell function, clinical characteristics, and follow-up care were assessed. Data were analyzed using descriptive and inferential statistics. Results: Among 1557 individuals with KPD, 11.6% underwent A testing, 20.2% underwent ß testing, and only 9.8% underwent both A and ß testing. HCPs were more likely to assess Aß status among those who were young, Black, and had new-onset diabetes (p<0.001). A-ß+ was the most common (53.9%), and A+ß+ was least common (5.9%) KPD. Clinical characteristics differed among subgroups, with ß- having a leaner BMI and more insulin dependence. Infection was the leading cause of DKA (37.9%), followed by unprovoked DKA (22.6%). Conclusion: Our study further validates and highlights the underutilization of Aß classification in KPD management and emphasizes the need for increased education among HCPs to improve care for people with KPD. Presentation: 6/1/2024

6745 Complete Remission of Type 1 Diabetes and the Honeymoon Phase: A Case Report

Abstract 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

12288 Diabetes Wearable Technology In Children Less Than Six Years At A Large Urban Diabetes Center

Abstract Disclosure: K. Citron-Zafrin: None. L. Richter: None. K. Williams: None. R. Gandica: None. I. Vargas: None. N. Leibel: None. Introduction/Background: Type 1 diabetes (T1D) is one of the most common chronic diseases in pediatrics. T1D is particularly challenging to manage in children under 6 years old due to unpredictable eating patterns, rapid growth, and risk of extreme blood glucose levels. Diabetes wearable technology (insulin pumps and continuous glucose monitors (CGMs)) has become increasingly prominent, but its use has not been well described in this age group. Objectives: We sought to characterize our experience with technology use in children with T1D less than 6 years old. Design/Methods: Retrospective chart review of 82 youth diagnosed with T1D before 6 years old, seen at our center from 2019-2023. Data was collected on demographic information, insurance type, use of insulin pump and CGM, hemoglobin A1c (A1c), diabetic ketoacidosis (DKA) and hypoglycemic events. We used chi-square statistics to compare variables in our population with reported national data. Results: In this cohort, 80% used insulin pumps and 100% used CGMs, an increase from previously reported data (56% insulin pump use and 44% CGM use in those less than 6yo, p<0.001). 54% had private insurance. There were more individuals with family members with T1D compared to reported data (35% vs. 22%, p=0.0041). The median age at diagnosis was 34 months, median time from diagnosis to pump start was 3.5 months. After diagnosis, 1 pump user and 1 multiple daily injections (MDI) user had DKA. One MDI user had hypoglycemia requiring intervention. Average A1C 12 months after diagnosis was 7.9% in the pump group and 8.2% in the MDI group. Hybrid closed loop pump users had an average A1C 6 months after placement of 7.7%. Conclusions: At our urban academic diabetes center, there was higher use of diabetes wearable technology as compared with previously reported data in this age group. There were more individuals with relatives with T1D compared to reported averages. The low rates of DKA and hypoglycemic events seen in this population support that these technologies can be used safely and soon after diagnosis. Although improved from national data, tight glycemic control remains a challenge in this very young age group. Presentation: 6/1/2024

6588 Insulin Autoimmune Syndrome Presenting with Severe Insulin Resistance and Recurrent Diabetic Ketoacidosis

Abstract Disclosure: E. Looi: None. R. Rosenberg: None. S. Sugar: None. H. Stone: None. A.W. Michels: None. D. Saxon: None. Background: Insulin autoimmune syndrome (IAS) is a rare cause of severe insulin resistance and is typically associated with intermittent hypoglycemia due to insulin antibodies (IA) with high binding capacity and low insulin affinity. However, consideration should be given for atypical presentation of IAS or co-presentation of IAS with type B insulin resistance syndrome (TBIRS) in the absence of hypoglycemia, as described in this case. Case: A 78-year-old African American female (BMI 21 kg/m2) with poorly controlled type 2 diabetes (A1c 11%) experienced recurrent episodes of diabetic ketoacidosis (DKA) despite adherence to escalating insulin doses (310 units daily, 5 u/kg/day). She was referred to endocrinology and continuous glucose monitoring revealed consistently elevated glucose levels (300-400 mg/dL) without hypoglycemia. She had normal renal function, hepatic function, and lipid panel. During a subsequent hospitalization, she required insulin drip rates of 50-70 u/hr. Insulin resistance workup revealed significantly elevated IA level (8.346, normal ≤ 0.010) measured using a fluid-phase radiobinding assay with high insulin binding capacity (1040 U insulin-binding/L blood) and low insulin binding affinity (1.9x107 M), which supported the diagnosis of IAS. Rheumatologic workup for other autoimmune diseases was negative. Due to recurrent DKA episodes, severe insulin resistance without obvious alternative cause, and lack of hypoglycemic events despite low IA binding affinity, co-morbid TBIRS was considered. As there are no commercially available insulin receptor antibody (IRAb) assays, diagnosis could not be confirmed before her condition worsened, and she was admitted for another episode of DKA within a week of being discharged. Due to clinical deterioration and high suspicion for IAS ± TBIRS, treatment with a combination of immunosuppressive agents was initiated in accordance with an NIH protocol (Klubo-Gwiezdzinska J, et al. 2018). Intravenous immune globulin (0.5g/kg/day) was administered over 2 days which resulted in a brief reprieve and followed by significant relapse. Two doses of rituximab (750 mg/m2) and 2 steroid pulses (dexamethasone 40 mg PO daily for 4 days) were then administered 2 weeks apart. Cyclophosphamide 100 mg daily was also started. Her hyperglycemia and insulin requirements subsequently improved, and she was eventually discharged with good glycemic control on a total daily dose of 40 units of insulin (0.5 u/kg/day), an 87.1% reduction in daily insulin requirement. Conclusion: This case demonstrates that IAS - although classically associated with hypoglycemic episodes - may also present with severe insulin resistance and recurrent DKA without hypoglycemia. Whether characterized by high IA binding capacity and affinity or coexisting with IRAb, a combination of immunosuppressants proved effective in treating both TBIRS and IAS in this instance. Presentation: 6/3/2024

8503 Analyzing Prescription Practices for Back-up Insulin and Glucagon in Type 1 Diabetes Patients Using Insulin Pumps: Findings From Cleveland Clinic

Abstract Disclosure: A. Iqbal: None. J. Ambalavanan: None. K. Alkwatli: None. P.P. Rao: None. Background: It is estimated that about 400,000 patients with type 1 diabetes (T1D) in the U.S. are using insulin pumps1. This number has been steadily increasing with expanding insurance coverage and newer, more convenient, user-friendly technology. Though these devices remarkably improve patients’ glycemic control, failure of these pumps, due to reasons such as clogging or kinking of tubing, air bubbles, pump display issues, site reaction/infection, is a frequently encountered problem. During these events, having a backup plan in the form of injectable insulin is essential to prevent severe hyperglycemia and diabetic ketoacidosis (DKA). Increasing insulin pump use also predisposes patients to severe hypoglycemia. In these cases, at-home glucagon administration can be lifesaving. Methods: Using the EPIC Cogito extracts and reporting service, data was extracted for adult patients seen at the Cleveland Clinic main campus between January 1, 2021, to January 1, 2023, using ICD codes for T1D and insulin pump status. Data collected included age, sex, prescription status for basal insulin, type of basal insulin, glucagon prescription, and current medication list.ResultsWe were able to analyze 86 patients (67% females, n=58; 33% male, n=28) with T1D utilizing an insulin pump. The average age was 48.6+18.18 years. Of the 86 patients, 51 (59%) had prescriptions for long-acting backup insulin. Only 21 patients (24%) had a prescription for glucagon. Discussion: Insulin pump failure is one of the most common causes of DKA in patients with T1D2. Educating patients on the use of long-acting injectable insulin in the event of pump failure and ensuring active prescription for every patient using an insulin pump at each visit can decrease the risk of DKA and prevent hospitalizations. Similarly, the use of a continuous subcutaneous insulin infusion (CSII) puts patients at high risk of hypoglycemia. Per Standards of Care in Diabetes 2024, glucagon should be prescribed in all patients using insulin3. Our analysis reveals that the practice of prescribing backup insulin and glucagon at Cleveland Clinic Institute needs significant improvement to potentially prevent DKA and severe hypoglycemia requiring hospitalization.

9185 Pembrolizumab-Induced New-Onset Type 1 Diabetes Mellitus: A Case Report

Abstract Disclosure: D. Teng: None. T.L. Connelly: None. M. Ahmad: None. R. Saeed: None. Introduction: Immune checkpoint inhibitors are becoming essential in the treatment of various cancers. Pembrolizumab is a monoclonal antibody that binds PD-1 receptors, thereby enabling an anti-tumor response by preventing T-cell suppression. Common side effects associated with pembrolizumab include thyroid disorders, hepatitis, pneumonitis, and acute kidney injury, among others. We describe an interesting case of a woman presenting with diabetic ketoacidosis (DKA) in the setting of pembrolizumab-associated new-onset type 1 diabetes mellitus, which was reported at 0.1% during initial clinical trials but is now being increasingly recognized as a complication of immune checkpoint therapy. Case Description: The patient is a 70-year-old female with past medical history notable for stage IIIA vulvar squamous cell carcinoma initially diagnosed and treated in 2017, with recurrence in 2022 and in 2023, at which point pembrolizumab therapy was initiated. Approximately one month after her first dose, the patient presented to the emergency department with palpitations, nausea, non-bloody vomiting, polydipsia, and non-bloody diarrhea. On arrival, the patient’s vital signs were as follows: 97.2 °F, BP 128/74 mmHg, heart rate 80 bpm, respiratory rate 18 per minute, and SpO2 100% on room air. No acute findings were noted on physical exam. Initial blood work was notable for: pH 7.146, lactate 2.4 mmol/L, bicarbonate 8 mmol/L, anion gap 37 mmol/L, creatinine 1.59 mg/dL, glucose 563 mg/dL, C-peptide 0.16 ng/mL, HbA1c 6.9%, and WBC 18.8 B/L with neutrophilic predominance. Urinalysis was notable for 4+ glucose and 4+ ketones. The patient was admitted to the progressive care unit and DKA protocol was initiated including the administration of IV fluids, insulin infusion, and electrolyte replacement. Additional blood work was unrevealing, including insulin autoantibodies <0.4 U/mL, negative islet cell IgG cytoplasmic autoantibodies, and negative anti-GAD65 antibodies. The patient was eventually discharged with outpatient Endocrinology follow-up. Discussion: Immunotherapy is quickly redefining the standard of care in the treatment of several types of malignancies through the leveraging of the body’s immune defense apparatus. Pembrolizumab prevents the deactivation of T-cells via the PD-1/PD-L1 pathway. Unfortunately, this also predisposes non-cancerous cells to autoimmune destruction by these T-cells. It is proposed that such is the mechanism by which pancreatic beta islet cells are destroyed in the setting of pembrolizumab use, thereby resulting in a rapid reduction in insulin production capability. New-onset type 1 diabetes complicated by DKA is potentially life-threatening, and so we believe this case highlights the need for both pre-treatment counseling as well as follow-up screening following initiation of pembrolizumab therapy. Presentation: 6/2/2024