1. Chronic Diabetes Case B Presented by: Owen Naidoo Abdullah Osman Christine Tanzil Ayse Togac

2. Ms SP, aged 34 years, has schizophrenia. She is currently being treated with Olanzapine (last 6 months) & is doing well.

3. However she has put on 7kg in weight since commencing the Olanzapine & her doctor is concerned that she is developing diabetes.

4. What is Olanzapine? An atypical antipsychotic, that is indicated in schizophrenia, related psychoses and acute mania. ADR’s: somnolence, weight gain, raised glucose, exacerbation of diabetes. C/I’s: CNS acting drugs, alcohol, smoking, drugs that increase the QTc interval.

5. TYPE 1 Diabetes Primarily immune mediated destruction of beta cells. Requires lifelong insulin:>15% of cases. Onset usually in earlier years Px is lean, ketonuria, later ketoacidosis.

6. TYPE 2 Diabetes Caused by either: abnormal insulin secretion failure to suppress hepatic glucose production insulin resistance in target tissue Strongly genetically determined in >80% of cases. Later onset Px is usually overweight

7. Describe the current guidelines for the diagnosis of diabetes as defined in Australia. PART I

8. SUMMARY OF DIAGNOSIS (Therapeutic Guidelines Online 2003)

9. Explain whether atypical antipsychotics such as Olanzapine can cause weight gain, hyperglycaemia or diabetes. PART II

10. 10 patients with Olanzapine- induced hyperglycaemia 8 patients Hyperglycaemia resolved 2 patients need oral hypoglycaemics Hyperglycaemia again Olanzapine discontinued In 2 patients Olanzapine rechallenged

11. Is the data consistent for Clozapine? What is the strength of this evidence? 7 patients with clozapine- induced hyperglycaemia 4 patients hyperglycaemia resolved 3 patients need insulin Hyperglycaemia again Clozapine discontinued Reintroduction of Clozapine

12. 82 patients treated with Clozapine over a 5 yr period 43 patients had 1 episode of increased BGL’s 19 patients had 2 episodes of increased BGL’s 30 patients were diagnosed with Diabetes Mellitus

14. What precautionary clinical chemistry tests should be performed & why? Full blood count Olanzapine may cause neutropenia as a rare adverse effect. Liver function tests Olanzapine may cause an elevation of liver transaminases as an infrequent adverse effect. Patients with hepatic dysfunction require a smaller dosage of Olanzapine.

15. (cont) Blood glucose Patients may have hyperglycaemia as a common adverse effect of Olanzapine usage. Renal Function tests Patients with renal dysfunction require a smaller dosage of Olanzapine.

16. Ms SP is a chain smoker. What impact does smoking have on Olanzapine? PART III

17. Effect of smoking????? Olanzapine is metabolised by CYP1A2. Smoking induces the CYP1A2 metabolism of Olanzapine. In smokers the clearance of Olanzapine is higher, on average, than the clearance in non-smokers. Therefore there may need to be an increase in the Olanzapine dose in a smoker. The clearance of Olanzapine is 33% lower and the terminal elimination half-life is 21% longer in non-smokers compared to smokers.

18. The techniques used in monitoring glucose in urine. PART IV

19. What does urine glucose testing measure? A urine glucose test determines whether or not glucose is present in the urine. Glucose will overflow into the urine only when the blood glucose level is high, that is above 10mmol/L

20. How is glucose in urine monitored? A small amount of urine is collected into a clean, dry container The dipstick analysis is performed as soon as possible after the collection (ideally within 30minutes). The reagent strip is dipped into the urine where it measures glucose levels using the glucose oxidase

21. (cont) The Glucose Oxidase method, is a sequential enzymatic reaction where glucose interacts with glucose oxidase to produce hydrogen peroxide, which oxidizes the indicator chemical to produce a colour change. The colour change s related to the amount of glucose present in the urine sample.

22. “The diagram on the disc…”

23. Problems associated with interpreting these results: a) It does not reflect your blood glucose level at the time of testing, instead, it gives an indication of your BGL over the past several hours b) It does not give any information about low blood glucose levels, as glucose is only found in the urine when the BGL is above 10mmol/L.

24. (cont) c) The results of a urine glucose test are influenced by the volume and concentration of urine that you pass d) Difficulty in interpreting colour changes e) If not read at specific time, results prone to error.