The Risk of Very Late-Onset Schizophrenia Following Diabetes Type 2 Onset: A Nationwide Population-Based Study of Midlife and Old-Age

Background and Hypothesis: Schizophrenia is an established Type 2 Diabetes (T2D) risk factor; while the reverse hypothesis is plausible, it remains untested. Study Design: This nationwide cohort study included all members (n = 99 567; Female: 52517, 52.7%) of a non-profit Israeli health maintenance organization born between 1932 and 1952. At cohort entry (aged M = 59.70, SD = 5.68) without histories of T2D or schizophrenia, the cohort was followed-up on average 14.47 (SD = 2.28) years for incident schizophrenia. Cox regression models were fit to quantify the association between T2D and schizophrenia risk with the Hazard Ratio (HR) and their 95% Confidence Intervals (CI), unadjusted and adjusted for 20 potential confounders in the primary analysis. Study Results: During follow-up, schizophrenia incidence per 10 000 person-years was 0.26 (95% CI, 0.21-0.32) in individuals with T2D and 0.12 (95% CI, 0.11-0.14) in those without. In the primary analysis, T2D onset was associated with a 50% increased risk of incident schizophrenia (adjusted hazard ratio = 1.53; 95% CI, 1.11–2.10; P = .009) compared with the absence of T2D. Generally, nine complementary analyses were consistent with the primary analysis results, showing T2D was associated with an increased risk of incident schizophrenia; the association showed minimal reverse causation and antidiabetic medication was not associated with schizophrenia risk. Conclusions: In this study, the onset of T2D was associated with an increased risk of schizophrenia. This suggests that the onset of T2D may require psychosis monitoring, which is relevant to healthcare providers and clinicians in psychiatry, geriatrics, and endocrinology.