Based on results of case series analysis and studies reported, patients with African-American ethnicity, first-degree family history of DM and baseline obesity appear to be at increased risk for the development of glucose dysregulation during atypical antipsychotic therapy. Almost all age groups have the potential risk to develop new-onset diabetes associated with the usage of atypical antipsychotics, although the fact that one-fourth of the reported cases were under age 35 is quite concerning. Weight gain during treatment does not appear to be a necessary factor associated with new-onset diabetes since 50% of the cases in our review who developed new-onset DM in our study manifested no weight gain; however, over 80% of patients were overweight before starting atypical agent therapy (Jin et al., 2002), suggesting that baseline weight is a significant risk factor for DM or DKA in patients taking atypical antipsychotics.
Although the large fraction of reported cases with DKA may illustrate a reporting bias toward interesting or extreme clinical findings, these cases obviously give a sense of the potential risk of therapy of atypical agents, a liability that must be managed by monitoring to adequately balance the risk-benefit ratio of treatment. The presence of DKA with type 2 DM is typically a marker of severe metabolic stress, with the development of ketosis occurring in those individuals with impaired insulin secretion due to decreased pancreatic insulin reserve. The absence of significant physical illness among these patients with DKA (e.g., infection) suggests that the atypical agent itself, by some unknown mechanism, may be a metabolic stressor in susceptible individuals. To our best knowledge, no research data have suggested the potential predictors of DKA in patients who developed new-onset DM during the treatment of atypical antipsychotics.
Nevertheless, clinicians should be aware of the relatively brief time course to the development of new-onset diabetes during atypical antipsychotic treatment in some patients, that the absence of significant weight gain is not uncommon with new-onset DM, and that the first presentation may indeed be diabetic ketoacidosis, a potentially life-threatening condition. Although there are no consensus guidelines on monitoring of serum glucose in those receiving atypical antipsychotics, recommendations in the Table are based upon the fact that diabetes is overrepresented in patients with schizophrenia and that this risk may be magnified with the use of atypical agents.