MECHANISMS OF ANTIPSYCHOTIC-INDUCED GLUCOSE DYSREGULATION AND INSULIN RESISTANCE

John W. Newcomer, M.D., 660 South Euclid Avenue, Box 8134, St. Louis, MO 63110-1002

Abnormalities in glucose regulation, including type 2 diabetes mellitus, are more common in schizophrenic patients than in the general population. New diagnostic criteria and screening recommendations for diabetes target early identification and treatment in an effort to limit health complications associated with hyperglycemia. Complications of hyperglycemia include retinopathy and nephropathy, and increased cardiovascular disease risk (eg, myocardial infarction and stroke). Plasma glucose thresholds for diagnosing diabetes are set to reflect glycemic thresholds for increased risk of retinopathy and nephropathy. However, cardiovascular disease risk increases continuously with increasing plasma glucose, beginning well below the diabetic threshold. Treatment with antipsychotic medications, particularly certain newer agents, has been associated with abnormalities in glucose and lipid metabolism, including diabetic ketoacidosis (DKA), hypertriglyceridemia, new-onset type 2 diabetes, and aggravation of preexisting type 1 and type 2 diabetes. Sensitive and validated assessments from several laboratories indicate differences in insulin resistance associated with different antipsychotic treatments. Antipsychotic effects on plasma glucose may be related in part to effects on glucose transport at the cellular level. Patients taking antipsychotics should be monitored for hyperglycemia, dyslipidemia, and weight gain, along with other risk factors for diabetes and cardiovascular disease.