Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis

Abstract

Schizophrenia is a lifelong mental disorder associated with cognitive dysfunctions. Comorbid metabolic dysregulations, such as diabetes and insulin resistance, may further deteriorate cognitive functions. It is therefore essential to investigate the effects of these metabolic disturbances on cognition in this population. A systematic review and meta-analysis following PRISMA guidelines was conducted using data from five databases: Medline, Embase, CENTRAL, Scopus, and Web of science. Of the 26 studies included, 9 were meta-analyzed with random effects model. The search was completed on November 23, 2023 and updated on April 2, 2025. We examined the cognitive functions of schizophrenia patients with and without diabetes or insulin resistance, using standardized mean differences (SMD) or mean differences (MD) as outcomes. The review section provides an overview of the literature on the relationship between glucose homeostasis and cognitive functions. The risk of bias was assessed using the QUIPS tool. There is a clear trend suggesting that diabetes exacerbates cognitive dysfunction in schizophrenia (global cognition: SMD=-0.26; P = 0.1087; 95% CI, -0.59 to 0.08), particularly in domains such as reasoning (SMD=-0.40; P = 0.0109, 95% CI -0.58 to -0.22) and processing speed (SMD=-0.43; P = 0.0005, 95% CI -0.52 to -0.35). Conflicting results were observed in studies on insulin resistance (global cognition: SMD=-0.12; P = 0.5890; 95% CI -0.91 to 0.68). Our findings suggest that glucose metabolism dysregulations might worsen cognitive dysfunctions in schizophrenia. However, further research is needed with larger samples and less heterogeneous studies to investigate if the effect is statistically significant. Addressing these metabolic issues could help improve cognitive and functional outcomes in schizophrenia patients.

Fig. 1

PRISMA 2020 flowchart showing the study selection process.

Fig. 2

Comparison of global cognitive functions in schizophrenia with and without diabetes. SMD standardized mean difference, SE standard error, CI confidence interval, HK Hartung-Knapp adjustment.

Fig. 3

Comparison of cognitive functions by different cognitive domains in schizophrenia with and without diabetes. (a) reasoning/problem-solving (b) working memory (c) processing speed. SMD standardized mean difference, SE standard error, CI confidence interval, HK Hartung-Knapp adjustment.

Fig. 4

Comparison of cognitive functions in schizophrenia with diabetes versus without diabetes in studies where cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). (a) global cognition; (b) attention; (c) delayed memory. CI confidence interval, SD standard deviation, MD mean difference, N sample size.

Fig. 5

Comparison of cognitive functions in schizophrenia with diabetes versus without diabetes in studies where cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). (d) immediate memory; ( e) language; (f) visuospatial. CI confidence interval, SD standard deviation, MD mean difference, N sample size.

Fig. 6

Comparison of global cognitive functions in schizophrenia with and without insulin resistance. SMD standardized mean difference, SE standard error, CI confidence interval, HK Hartung-Knapp adjustment, IR insulin resistance, RBANS Repeatable Battery for the Assessment of Neuropsychological Status, BACS Brief Assessment of Cognition in Schizophrenia, MCCB MATRICS Consensus Cognitive Battery.