MON-657 Unmasking a Rare Adverse Event: Olanzapine-Induced Diabetic Ketoacidosis in a Type 1 Diabetes Mellitus Patient

Abstract Disclosure: S. Abou Khachfe: None. A. Patel: None. C. Guillen-Lopez: None. M. Ali: None. P. Subarajan: None. Introduction: Second-generation antipsychotics (SGAs) have been associated with metabolic disruptions, such as worsening hyperglycemia and new-onset diabetes. The risk of developing diabetic ketoacidosis (DKA) with SGAs is approximately ten times higher than that observed in the general population. DKA was more commonly associated with pre-existing insulin resistance, although some reported cases have occurred without a history of diabetes. The median time to DKA onset was reported as five months, but onset has been documented to be as rapid as ten days or weeks. Olanzapine represents 36% of the associated antipsychotics, followed by aripiprazole at 24%, risperidone at 24%, clozapine at 12%, and quetiapine at 4%. The underlying mechanism of SGAs-induced hyperglycemia is multifactorial, involving impairments in insulin secretion, reductions in insulin sensitivity, and decreased whole-body carbohydrate oxidation. Although some cases reported improvement in hyperglycemia after medication discontinuation, it is crucial to note that acute hyperglycemic changes remain potent even after chronic treatment, raising the risk of cardio-metabolic complications. We present to you a case of rapid-onset DKA in a female with type 1 diabetes mellitus (T1DM) after SGA initiation. Case: A 27-year-old female with a past medical history of T1DM at 13 weeks gestation presented to the emergency department with hyperemesis gravidarum. During the hospitalization, her fluctuating blood glucose levels (ranging from 80-180 mg/dL) were managed with a basal and bolus insulin regimen. During the third week of hospitalization, olanzapine was initiated to address her psychogenic nonepileptic seizures. Within 48 hours, the patient was in DKA: with blood glucose in the 200s, a beta-hydroxybutyrate level of 3.1mmol/L (0.0-0.3 mmol/L), and an anion gap of 18 mmol/L (4-12 mmol/L). The patient was admitted to the ICU and treated with DKA protocol. Since SGA therapy was not efficacious for this patient, olanzapine was stopped. DKA resolved, but the patient did have a persistent disproportionate insulin requirement. Discussion: This case highlights the importance of raising awareness about the need for close monitoring for SGA-associated exacerbation of hyperglycemic crises in individuals with an already elevated underlying risk, such as insulin deficient state and pregnancy. With the growing popularity of olanzapine in treating psychosis and mood disorders, clear guidelines for controlling blood glucose levels are crucial, irrespective of personal or family diabetes history. Preventive measures, including regular risk assessment and diabetes screening before and after antipsychotic therapy, are imperative. Clinicians should closely monitor susceptible patients, considering the continuation of SGA treatment alongside proper diabetes management or screening protocols for metabolic complications. Presentation: Monday, July 14, 2025