Insulin Sensitivity/Secretion/ Glucose in Schizophrenia

Massachusetts General Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

The investigators propose to study the effects of the atypical antipsychotic agents, clozapine, risperidone, and olanzapine on utilization of glucose, insulin secretion and insulin sensitivity in schizophrenic patients by using Bergman's Minimal Model intravenous glucose tolerance test. Atypical antipsychotic agents cause fewer extrapyramidal side effects than conventional neuroleptics but have a variety of other side effects. Obesity is a known side effect of neuroleptics and recent reports in the literature have linked clozapine with weight gain. Response to clozapine has been significantly correlated with weight gain in two studies. Other atypical antipsychotic agents also appear to cause some degree of weight gain. 13-85% of patients and the average weight gain was 9.0-24.7 lb. One study found 75% of patients gained at least 10 lbs. The mechanism for the weight gain is unclear. By increasing a patient's risk of obesity, antipsychotic agents may be placing patients at risk for associated morbidity and mortality. Patients who gain greater than 10% of their total body weight are at risk for developing weight associated conditins such as hypertension and non-insulin dependent diabetes. A review of the literature found eight cases of hyperglycemia or diabetic ketoacidosis associated with clozapine. Seven cases require no insulin treatment after resolution of the acute hyperglycemic event. However, in the investigators experience, many patients that develop clozapine associated diabetes require oral agents or in many cases insulin. Cases are beginning to emerge of olanzapine associated diabetes mellitus. To the investigators knowledge, there are no published reports of risperidone associated diabetes mellitus. The mechanism of clozapine and olanzapine associated glucose abnormalities is unknown. both clozapine and olanzapine may exacerbate a preexisting subclinical diabetic disorder or promote glucose metabolic abnormalities. The investigators hypothesize that the glucose abnormalities are not simply related to weight gain but are a direct effect upon glucose metabolism, insulin secretion and insulin sensitivity.