In the on-going study in progress we use an extensive battery of assessments to investigate a)fasting levels of glucose and lipids at baseline and monthly during 5 months of treatment, b) glucose tolerance tests to investigate glucose and insulin abnormalities after a glucose load at baseline and during study treatment, and c)the effects of treatment with olanzapine and risperidone of post prandial glucose metabolism after a fatty meal (as detailed in the body of the proposal). Recent studies have shown that increased postprandial lipidemia is an important feature of many patients with type 2 diabetes and atherosclerosis. In addition to the biochemical measures, we will also assess clinical effects (PANSS and CGI ratings) and other side-effects (weight gain, appetite, somnolence, and EPS and TD). The specific plan calls for inpatients in a tertiary care hospital to be randomly assigned to olanzapine or risperidone, using a stratified random assignment procedure, and treated for five months with either olanzapine or risperidone. We estimate that we will have to enroll a sample of approximately 50-55 patients to obtain 46 acceptable complete cases(as specified in proposal below). On the basis of preliminary results from our prior and ongoing studies we predict no significant increase in glucose abnormalities from baseline during chronic treatment with olanzapine and no significant differences in development of glucose abnormalities in patients in patient treated with olanzapine and risperidone.
Additional measures being investigated include: comparison of olanzapine and risperidone in glucose and lipid responses to a fatty meal, ghrelin changes in response to a fatty mean, and CRP and IL-6, and thyroid and prolactin response to five months of treatment with the two drugs.
