Schizophrenia and Psychosis
Longstanding evidence suggests that schizophrenia is associated with type 2 diabetes mellitus (DM2). The research includes maternal and birth studies that identify common risk factors for both conditions, including nulliparity, gestational diabetes, preeclampsia, birth weight, and season of birth.1 Studies before the advent of antipsychotics showed an increased prevalence of abnormal glucose metabolism in patients with schizophrenia, albeit with methodological limitations.2 There is also evidence for impaired glucose tolerance and insulin resistance in patients with first-episode psychosis who are either antipsychotic-naïve or have minimal antipsychotic exposure.3,4
These findings suggest that some of the increased risk of DM2 in schizophrenia may be independent of antipsychotic medications and involve host-agent-environment interactions. However, this hypothesis has largely been overshadowed by known metabolic adverse effects of second-generation antipsychotic medications, which increase the risk of DM2.
Schizophrenia is associated with an increased risk of the metabolic syndrome, a constellation of metabolic risk factors—including abnormal glucose tolerance—associated with cardiovascular disease morbidity and mortality.5 In an earlier study, patients with schizophrenia and other non-affective psychoses (NAP) and a parental history of DM2 were found to have a 3.7-fold increased odds of comorbid DM2 compared with patients without this parental history.6
A meta-analysis was undertaken to understand the association between a family history of DM2 and DM2 comorbidity in patients with NAP.7 Studies were identified by systematically searching Medline, PsycInfo, Web of Science, and Science Direct. Non-affective psychosis was defined to include schizophrenia, schizophreniform disorder, brief psychotic disorder, delusional disorder, schizoaffective disorder, and psychotic disorder not otherwise specified. One hundred thirty-six potential studies were identified; however, most were excluded because of missing family history data about DM2, or because the diagnoses were primarily affective psychosis. Case reports were also excluded. After a detailed review, 10 studies met the inclusion criteria
Data used included number of subjects with and without a family history of DM2 based on comorbid DM2 status, as well as other clinical and demographic variables. Effect size estimates (odds ratios [ORs] and 95% confidence intervals [95% CIs]) were calculated using the random effects method. Given significant between-study heterogeneity, a sensitivity analysis and a series of meta-regressions to explore possible moderating variables we used to account for heterogeneity (eg, age, sex, geographic region, body mass index, year of publication, study quality).
The total sample consisted of 3780 patients with non-affective psychoses, including 804 subjects with a family history of DM2 and 2976 without a family history of DM2. A family history of DM2 was associated with more than a four-fold increased odds of comorbid DM2 (OR = 4.3, 95% CI 2.9-6.4, P < .001), with significant between-study heterogeneity. In sensitivity analyses, after removing two outlying studies with the highest OR, the association remained significant (OR = 3.3, 95% CI 2.6-4.3, P < .001), but between-study heterogeneity was no longer significant. A funnel plot and Egger’s test were not significant for publication bias, although findings should be interpreted with some caution given the small number of studies. In meta-regression, there was a significant, positive association with age, but all other potential moderating factors were unrelated to the association between comorbid DM2 and family history of DM2.
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1. Kandhal P, Miller BJ. Shared early life risk factors for schizophrenia and diabetes. Minerva Psichiatrica. 2013;54:197-210.
2. Kohen D. Diabetes mellitus and schizophrenia: historical perspective. Br J Psychiatry. 2004;184:64-66.
3. Greenhalgh AM, Gonzalez-Blanco, L, Garcia-Rizo C. et al. Meta-analysis of glucose tolerance, insulin, and insulin resistance in antipsychotic-naïve patients with nonaffective psychosis. Schizophr Res. 2017;179:57-63.
4. Perry BI, McIntosh G, Weich S, et al. The association between first-episode psychosis and abnormal glycaemic control: systematic review and meta-analysis. Lancet Psychiatry. 2011;11:1049-1058.
5. McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005;80:19-32.
6. Miller BJ, Goldsmith DR, Paletta N, et al. Parental type 2 diabetes in patients with non-affective psychosis. Schizophr Res. 2016;175:223-225.
7. Chung J, Miller BJ. Meta-analysis of comorbid diabetes and family history of diabetes in nonaffective psychosis. Schizophr Res. 2019 (In press).
8. Papazafiropoulou AK, Papanas N, Melidonis A, Maltezos E. Family history of type 2 diabetes: does having a diabetic parent Increase the risk? Curr Diabetes Rev. 2017;13:19-25.