Volume 1 number 1 Summer 2003
Special issue for the abstracts of the 7th Pan Arab Conference on Diabetes
PACD7 , 25 – 28 March 2003 Cairo

Abstract Number : 44
Case Report

Clozapine Induced Diabetic Ketoacidosis
Alyi Misha`l M.D., Khalil Alsoutary, M.D., FACE,

Introduction:
Clozapine is an atypical antipsychotic that is associated with development of diabetes mellitus, increase body weight and other side effects. There were several reports IB the literature that described patients’ diabetic Ketoacidosis with Clozapine.

Case presentation:
A 31-year, Jordanian male with chronic schizophrenia was treated with Clozapine 800mg per day for 3 months, his weight increased from 82 kg to 92 kg and he was treated with metformin and glibenclamide, but his blood sugar was consistently elevated. On Sept.30 he presented to the Emergency room with 2 days history of Vomiting, confusion abdominal pain and sleepiness. His blood sugar was elevated at 444mg/dl (24 mmol/L.), Serum Acetone positive, Arterial blood gases showed metabolic acidosis:
PH =7.359,HCO3 18.5 mmol/l, .PO2 75.3 Urea was 13mg/dl, Na 141 mmol/l, and K was 3.5 mmol/l. After treatment with IV fluids and Insulin infusion at 3-5 units/hr, and discontinuation of Clozapine patient improved and his sugar was controlled and serum acetone became negative, He was able to tolerate oral feeding and so twice daily mixed insulin was initiated and patient was discharged on mixtard insulin 70/30 25 units in am, and 15 units in PM. His antipsychotic medication changed to fluphenazine, haloperidol and kemadrine, and home glucose monitoring results were 120-220mg/dl.

Discussion:
Clozapine is an atypical anti psychotic that is associated with several side effects including life-threatening agranulocytosis in1 %, Hypertension, weight gainsedation and sialorrhea.
There are reports of 242 cases of new onset diabetes hat developed on Clozapine, and 80 cases of diabetic Ketoacidosis on patients taking Clozapine. Avram¹ described a case of Clozapine induced Ketoacidosis with complete resolution to euglycemia after dscontuation of the drug, and he demonstrated insulin resistance and suppression of Beta cells function in that patient., by using Oral Glucose Tolerance Test, IV Glucose Tolerance and euglycemia clamp. Another report by Perry et al of 2 patients with diabetes mellitus developed on Clozapine therapy. A recent review compared weight gain after 10 wks of treatment between typical and a typical antipsychotics, showed that in patients on Clozapine weight gain was 4.45 kg, followed by olazepine 4.15 kg, Sertindole 2.92 kg followed by risperidone 2.1kg. Data was insufficient for quitapine.

Conclusion:
Due to increasing reports of diabetes mellitus and Impaired glucose tolerance associated with Clozapine and other atypical antipsychotics, patients should be monitored carefully on these medications and if ketoacidoi develop, patients should be changed to other antipsychotic drugs whenever possible.

References:
1) Abram, A., Patel V, Taylor HC.
Euglycemic clamp in Clozapine induced diabetic Ketoacidosis
Annals of Pharmacotherapy 2001,35:1381-1387

2) Heidi Wehring B.A.Bruce Alexander and Paul J. Perry.PhD
Pharmacotherapy 20(7): 844-847,2000

3) Medscape WebPages on Diabetes Mellitus associated with Clozapine therapy

OnlineDiabetes Journal, All rights reserved