Quetiapine-induced Hypoglycemia in an Elderly Non-diabetic Patient with Dementia

Introduction:
Quetiapine is a second-generation antipsychotic agent (SGA) widely prescribed for the treatment of psychotic and mood disorders. In elderly patients, quetiapine is often used to treat psychotic symptoms associated with dementia. A metabolic syndrome phenotype of weight gain, hyperglycemia, and hyperlipidemia is a potential adverse effect of SGA’s, though hypoglycemia caused by SGA’s is documented.  We report a case of quetiapine-induced hypoglycemia in a non-diabetic patient.

Case Description:
A 79-year-old male with Lewy body dementia was admitted to hospital for management of a myocardial infarction. The patient had no history of diabetes mellitus, renal failure, or hepatic insufficiency, and nobody living with the patient was treated for diabetes.  Plasma glucose on admission was 84 mg/dL. Quetiapine was started to control delirium, but within 24 h the patient had worsening confusion and a capillary blood glucose (CBG) measurement of 52 mg/dL. Symptoms improved with administration of dextrose, and the patient ultimately required a 10% dextrose infusion to maintain CBG’s >80 mg/dL.  An ACTH-stimulation test (30 min stimulated cortisol 24.8 µg/dL, expected >18) and hypoglycemic medications panel (sulfonylureas and meglitinides) were unremarkable. Quetiapine was stopped, and hypoglycemia resolved. No hypoglycemia occurred during a subsequent 48-h diagnostic fast followed by a mixed meal tolerance test. Due to the patient’s advanced age and comorbidities, it was decided not re-challenge with quetiapine and observe for recurrence of hypoglycemia.

Discussion:
Hypoglycemia is a rare complication of SGA’s, and diagnosis may be delayed or missed in patients with baseline confusion or agitation. In addition to quetiapine, there are case reports of hypoglycemia occurring during treatment with risperidone, olanzapine, aripiprazole, and paliperidone. Clozapine and olanzapine increase insulin release from isolated pancreatic islets in vitro, though quetiapine did not demonstrate this effect. However, endogenous hyperinsulinemia has been documented in case reports of quetiapine-induced hypoglycemia. The physiologic pathway by which SGA’s increase insulin release is unknown; some authors have focused on the antagonism of M1 muscarinic receptors, but the muscarinic M1 receptor antagonist pirenzepine has been demonstrated to reduce insulin secretion induced by the muscarinic receptor agonist carbachol from isolated rat pancreatic islets in vitro. Though the mechanism by which hypoglycemia occurs is unclear, this case demonstrates that hypoglycemia should be considered in patients with worsening mental status during treatment with SGA’s.