Clozapine Induced Insulin Dependence

Abstract

Background: Antipsychotic medications come with an array of potential side effects in a difficult-to-treat population, particularly if management of other comorbidities is required. A review of the literature shows some studies have discussed the possibility of antipsychotic medication inducing hyperglycemia by blocking pancreatic M3 receptors. Other studies have shown dramatic worsening of metabolic parameters in patients who already have Type 2 Diabetes Mellitus after starting Clozapine. Clinical Case: A 23 year old African American Male with a past history of treatment resistant Schizophrenia presented to the ED with hyperglycemia and altered mental status. Blood sugar 489 mg/dL, anion gap 28 mmol/L, bicarb 13 mmol/L, white Blood Cell count 9.0 x10^3/cmm. Urine positive for Ketones. Chest Xray and EKG were normal, there were no obvious signs of infection. This was the sixth admission for Diabetic Ketoacidosis (DKA) in the past 10 months. Antibodies obtained showed negative Glutamic Acid Decarboxylase Autoantibodies (<5 IU/mL), Islet Cell Antibody IgG, Zinc Transporter 8 Antibody (<10 U/mL), IA-2 (<5.4 U/mL). C-peptide levels were in the low normal range (1.12 ng/mL) with a blood sugar 204 mg/dL. Prior to 10 months ago, the patient did not have a diagnosis of diabetes, with labs showing expected normal fasting blood sugar levels (90s mg/dL) and triglyceride levels of 150 - 200 mg/dL. One month after starting Clozapine for treatment resistant Schizophrenia, A1c doubled to 12.3%, Triglycerides increased to 1,378 mg/dL. The patient had been insulin dependent since the time of starting Clozapine. On this admission, Clozapine was held, DKA resolved with intravenous fluid, potassium replacement, and insulin drip. Repeat testing of c-peptide with blood glucose levels analyzed with the Homeostasis Model Assessment (HOMA) showed increasing HOMA%S (from 93% to 174%) and decreasing HOMA-IR with stopping Clozapine. Psychiatry recommended Clozapine as required treatment of his Schizophrenia, therefore the patient required chronic insulin. Conclusion: This case study shows Clozapine as the only major change in medications or lifestyle in this patient’s case. He demonstrated severe hyperglycemia and development of Diabetes Mellitus within a 4-week period of medication initiation as evidenced by multiple admissions for DKA, with low/normal C-peptide levels and insulin resistance. He has since been managed as a patient with Type 1 Diabetes. Clinicians should take a multidisciplinary approach to clinical surveillance during changes in schizophrenia treatment, particularly with second generation antipsychotics such as Clozapine, with attention to metabolic derangements including DKA.