Impaired Glucose Homeostasis in First-Episode Schizophrenia
Schizophrenia is associated with an increased risk of type 2 diabetes. However, it is not clear whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term treatment. As a result, a study published in JAMA Psychiatry (2017;74:261-269) conducted a meta-analysis examining whether individuals with first-episode schizophrenia already exhibit alterations in glucose homeostasis compared with controls.
For the study, the EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining measures of glucose homeostasis in antipsychotic-naive individuals with first-episode schizophrenia compared with individuals serving as controls. Study selection included case-control studies reporting on fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in first-episode antipsychotic-naive individuals with first-episode schizophrenia compared with healthy individuals serving as controls. Two independent investigators selected the studies. Two independent investigators extracted study-level data for a random-effects meta-analysis. Standardized mean differences in fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and HbA1c levels were calculated. Sensitivity analyses examining the effect of body mass index, diet and exercise, race/ethnicity, and minimal (<2 weeks) antipsychotic exposure were performed.
Results showed that of the 3,660 citations retrieved, 16 case-control studies comprising 15 samples met inclusion criteria. The overall sample included 731 patients and 614 controls. Fasting plasma glucose levels (P=0.03), plasma glucose levels after an oral glucose tolerance test (P=0.007), fasting plasma insulin levels (P=0.01), and insulin resistance (homeostatic model assessment of insulin resistance) (P=0.001) were all significantly elevated in patients compared with controls. However, HbA1c levels (P=0.55) were not altered in patients compared with controls.
According to the authors, the findings show that glucose homeostasis is altered from illness onset in schizophrenia, indicating that patients are at increased risk of diabetes as a result. The authors added that this finding has implications for the monitoring and treatment choice for patients with schizophrenia.