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 o...

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Main Authors: Alexander Kancsev, Eszter Éva Virág-Tulassay, Marie Anne Engh, Szilvia Kiss-Dala, András Attila Horváth, Péter Hegyi, Szabolcs Kéri
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-06225-0
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author Alexander Kancsev
Eszter Éva Virág-Tulassay
Marie Anne Engh
Szilvia Kiss-Dala
András Attila Horváth
Péter Hegyi
Szabolcs Kéri
author_facet Alexander Kancsev
Eszter Éva Virág-Tulassay
Marie Anne Engh
Szilvia Kiss-Dala
András Attila Horváth
Péter Hegyi
Szabolcs Kéri
author_sort Alexander Kancsev
collection DOAJ
description 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.
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spelling doaj-art-ca5defce76ee47c3a2cede6aff2b98182025-08-20T03:03:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-06225-0Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysisAlexander Kancsev0Eszter Éva Virág-Tulassay1Marie Anne Engh2Szilvia Kiss-Dala3András Attila Horváth4Péter Hegyi5Szabolcs Kéri6Centre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityCentre for Translational Medicine, Semmelweis UniversityAbstract 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.https://doi.org/10.1038/s41598-025-06225-0
spellingShingle Alexander Kancsev
Eszter Éva Virág-Tulassay
Marie Anne Engh
Szilvia Kiss-Dala
András Attila Horváth
Péter Hegyi
Szabolcs Kéri
Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
Scientific Reports
title Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
title_full Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
title_fullStr Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
title_full_unstemmed Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
title_short Glucose homeostasis and cognitive functions in schizophrenia: a systematic review and meta-analysis
title_sort glucose homeostasis and cognitive functions in schizophrenia a systematic review and meta analysis
url https://doi.org/10.1038/s41598-025-06225-0
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