Two of the individuals receiving olanzapine developed diabetic ketoacidosis, but one of them subsequently became normoglycemic after olanzapine discontinuation and switch in antipsychotic treatment to risperidone. Limited prospective data exist, but one series was reported at the American Psychiatric Association 1999 Institute on Psychiatric Services held in New Orleans. Although the patients with diabetes or elevated baseline glucose appeared more susceptible to hyperglycemia during olanzapine treatment, Smith noted that several of the patients who developed hyperglycemia after starting treatment had neither diabetes nor elevated blood glucose levels at baseline. In discussing this and previously reported cases of olanzapine-induced glucose dysregulation, Bettinger et al. The possibility that clozapine impairs insulin response to glucose was investigated by researchers in Stockholm, Sweden.
Low levels are a marker of decreased levels of growth hormone, which is associated with weight gain.
The researchers noted that elevated insulin levels correlated with higher serum concentrations of clozapine, but not with traditional neuroleptics, suggesting that clozapine can enhance insulin secretion. Increased insulin secretion, reasoned the researchers, may ultimately lead to insulin resistance. Given the link between reduced growth hormone and weight gain, they speculated that this could contribute to the weight gain associated with clozapine. Evidence of insulin resistance with clozapine treatment has been sought by other investigators. Yazici et al.