Metabolic studies of atypical antipsychotic agents and diabetes

Interpretation of case reports of antipsychotic-associated diabetes mellitus is complicated by the high background risk for diabetes in those with chronic serious mental disorders and the high prevalence of asymptomatic undiagnosed diabetes in the general population. Controlled metabolic studies are needed to provide more definitive information concerning the types of metabolic effects that may be associated with the atypical antipsychotics. Therefore, this article reviews what has been learned from metabolic studies concerning the types of disturbances involved in the etiology of type 2 diabetes and presents findings from metabolic studies done with antipsychotics. Glucose tolerance studies involving both conventional and atypical antipsychotics are reviewed first. Findings from insulin sensitivity studies are then presented. These include clamp studies of the effects of atypical antipsychotics on insulin sensitivity and beta-cell function in both healthy subjects and patients with schizophrenia. Studies evaluating the effects of the atypical antipsychotics on insulin secretion are then reviewed. The article concludes with an evaluation of the evidence and suggestions for future research in this area.