Glucose homeostasis in unaffected first-degree relatives of schizophrenia patients: A systematic review and meta-analysis.

It has been proposed that type 2 diabetes and schizophrenia-spectrum disorders share overlapping genetic backgrounds. Therefore, we aimed to perform a systematic review and meta-analysis of studies comparing fasting levels of glucose and insulin, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glucose levels during the oral glucose tolerance test (OGTT) and the levels of glycated hemoglobin (HbA1c) in unaffected first-degree relatives of patients with schizophrenia and controls. Online searches covered the publication period from database inception until May 8th 2020. Meta-analyses were performed using random-effects models with Hedges' g as the effect size estimate. Out of 2556 records identified, 12 studies representing 672 relatives of schizophrenia patients and 6446 controls were found to be eligible. There were no significant differences in fasting levels of glucose (g = 0.54, 95%CI = -0.26 to 1.35, p = 0.188) and insulin (g = 0.07, 95%CI = -0.14 to 0.29, p = 0.491), HOMA-IR (g = 0.12, 95%CI = -0.19 to 0.43, p = 0.433), and the levels of HbA1c (g = 0.38, 95%CI = -0.02 to 0.77, p = 0.061) between relatives of schizophrenia patients and controls. Two studies demonstrated significantly higher 2-hour glucose levels during OGTT in relatives of patients with schizophrenia (g = 0.90, 95%CI = 0.49 to 1.31, p < 0.001). Our findings do not support the hypothesis that familial liability to psychosis is related to altered fasting parameters of glucose homeostasis. However, this population might show impaired glucose tolerance. More studies are needed to confirm these observations.