Case Presentation: A 47-year-old woman with migraines, bipolar disorder, and hypothyroidism presented with a 2-day headache that was not improving with sumatriptan. She also complained of generalized weakness, dizziness, nausea, and vomiting. Workup revealed diabetic ketoacidosis, with blood glucose 530 mg/dL, venous pH 7.02, bicarbonate of 8 mmol/L, and anion gap 29.
The patient had no prior history of diabetes mellitus. On further review, her primary care physician had initiated aripiprazole 4 months prior due to occasional manic episodes with cognitive behavioral therapy alone. The patient recalled increased appetite and weight gain during that period. One month prior to admission, her dose of aripiprazole was increased and she subsequently began experiencing more frequent headaches, polydipsia, and polyuria. On hospital admission, hemoglobin A1C was 13.0%. The patient was treated for diabetic ketoacidosis and discharged on hospital day 6 with a new home insulin regimen.
Discussion: The popularity of atypical antipsychotics has increased in recent years due to their tolerability and lower risk of extrapyramidal side effects compared to first-generation antipsychotics. Metabolic complications associated with atypical antipsychotics are partially mediated by changes in dopamine and serotonin receptor signaling that lead to hyperphagia. Weight gain, insulin resistance, and lipid dysregulation are more strongly associated with antipsychotics like olanzapine and clozapine than aripiprazole and ziprasidone. Olanzapine induces insulin resistance and causes significant elevations in postprandial insulin, glucagon-like peptide 1, and glucagon. While aripiprazole does not have major effects on postprandial hormones, it has been shown to induce insulin resistance. Aripiprazole is often used to treat psychiatric conditions in patients with comorbid obesity or metabolic conditions because it is considered metabolically sparing relative to other atypical antipsychotics. This case of new onset type 2 diabetes mellitus presenting as diabetic ketoacidosis due to the atypical antipsychotic aripiprazole illustrates the importance of closely monitoring patients starting or changing doses of antipsychotics.
Conclusions: Patients exposed to atypical antipsychotics have a 10-fold increased risk of diabetic ketoacidosis compared to the general population, and must be educated on symptoms that should prompt further evaluation.