Metabolic Changes in Schizophrenia May Predate Antipsychotic Use

By the time a person with schizophrenia presents at the onset of the illness, he or she may already be experiencing glucose dysregulation—increasing the risk of type 2 diabetes, a meta-analysis published today in JAMA Psychiatry reports. The findings highlight the importance of prescribing antipsychotics at a dose that limits the metabolic impact and educating patients about diet, exercise, and diabetic screening as early as possible after diagnosis.

While rates of type 2 diabetes are known to be two to three times higher in patients with schizophrenia than the general population, it was previously unknown whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term antipsychotic treatment. 

Oliver D. Howes, Ph.D., of the Imperial College London and colleagues conducted a systematic review of case-control studies reporting on fasting plasma glucose levels, fasting insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in individuals with first-episode schizophrenia who had minimal (≤2 weeks of antipsychotic treatment) or no exposure to antipsychotics. A total of 16 case-control studies were included in the analysis, including 731 patients and 614 controls. Fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, and insulin resistance were all significantly elevated in patients compared with controls, but HbA1c levels were not altered in patients compared with controls. 

The findings “indicate that individuals with schizophrenia present at the onset of illness with an already vulnerable phenotype for the development of type 2 diabetes,” the authors wrote. “Given that several antipsychotic drugs may worsen glucose regulation, there is thus a responsibility placed on the treating clinician to select an appropriate antipsychotic at an appropriate dose so as to limit the metabolic impact of treatment. Furthermore, the association between schizophrenia and glucose dysregulation suggests that patients should be educated regarding diet and physical exercise, as well as diabetic screening, and offered early lifestyle and pharmacologic interventions to combat the risk of progression to type 2 diabetes.”

For related information, see the Psychiatric News article “Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth” and the Psychiatric Services article “Health Promotion for Young Adults With Serious Mental Illness.”

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