Clozapine is one of the commonly used atypical antipsychotics. Several pharmacoepidemiologic studies have supported the notion that atypical antipsychotics may raise the risk of diabetes. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available. This study aims to clarify the diabetogenic effect of clozapine on the blood glucose level and on the cellular level by histopathological and immunohistochemical examination of pancreas. Twenty adult albino male rats were divided into two groups; first one as a control group received distilled water orally for 90 days. The other group received 13 mg of clozapine orally daily for the same duration. The rats were sacrificed and blood samples for assessment of glucose level were obtained. The pancreas was processed for histopathological, histochemical and immunohistochemical examination. The results showed hyperglycaemia in the clozapine treated group. Hisopathological examination of the pancreas of treated animals showed many large sized islets of Langerhans, sprouting of new islets from a pre-existing one and many small scattered islets within pancreatic lobules denoting hyperplastic changes. Also, some islets showed apoptotic cells and others showed lymphocytic infiltration. Endocrine-like masses of cells could be observed in relation to many interlobular ducts. Interlobular and interacinar fibrosis was observed by using masson's trichrome stain. PAS reaction revealed increased thickness of the basement membrane of the islets capillaries. Immunohistochemical staining with anti-insulin antibody showed strong staining of the hyperplastic islets of treated animals.
Histopathological and immunohistochemical observations suggested that clozapine treatment has a diabetogenic effect on the pancreatic islets of Langerhans. The pathogenesis of clozapine-associated diabetes is very similar to type 2 diabetes mellitus.