Diabetes exerts a causal impact on the nervous system within the right hippocampus: substantiated by genetic data

TY - JOUR

T1 - Diabetes exerts a causal impact on the nervous system within the right hippocampus

T2 - substantiated by genetic data

AU - Long, Qian

AU - Huang, Piao

AU - Kuang, Jian

AU - Huang, Yu

AU - Guan, Haixia

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

PY - 2025/2

Y1 - 2025/2

N2 - Introduction: Diabetes and neuronal loss in the hippocampus have been observed to be correlated in several studies; however, the exact causality of this association remains uncertain. This study aims to explore the potential causal relationship between diabetes and the hippocampal nervous system. Methods: We utilized the two-sample Mendelian randomization (MR) analysis to investigate the potential causal connection between diabetes and the hippocampal nervous system. The summary statistics of Genome-wide association study (GWAS) for diabetes and hippocampus neuroimaging measurement were acquired from published GWASs, all of which were based on European ancestry. Several two-sample MR analyses were conducted in this study, utilizing inverse-variance weighted (IVW), MR Egger, and Weight-median methods. To ensure the reliability of the results and identify any horizontal pleiotropy, sensitivity analyses were undertaken using Cochran’s Q test and the MR-PRESSO global test. Results: Causal associations were found between diabetes and the nervous system in the hippocampus. Type 1 and type 2 diabetes were both identified as having adverse causal connections with the right hippocampal nervous system. This was supported by specific ranges of IVW-OR values (P < 0.05). The consistency of the sensitivity analyses further reinforced the main findings, revealing no significant heterogeneity or presence of horizontal pleiotropy. Conclusions: This study delved into the causal associations between diabetes and the hippocampal nervous system, revealing that both type 1 and type 2 diabetes have detrimental effects on the right hippocampal nervous system. Our findings have significant clinical implications as they indicate that diabetes may play a role in the decline of neurons in the right hippocampus among European populations, often resulting in cognitive decline.

AB - Introduction: Diabetes and neuronal loss in the hippocampus have been observed to be correlated in several studies; however, the exact causality of this association remains uncertain. This study aims to explore the potential causal relationship between diabetes and the hippocampal nervous system. Methods: We utilized the two-sample Mendelian randomization (MR) analysis to investigate the potential causal connection between diabetes and the hippocampal nervous system. The summary statistics of Genome-wide association study (GWAS) for diabetes and hippocampus neuroimaging measurement were acquired from published GWASs, all of which were based on European ancestry. Several two-sample MR analyses were conducted in this study, utilizing inverse-variance weighted (IVW), MR Egger, and Weight-median methods. To ensure the reliability of the results and identify any horizontal pleiotropy, sensitivity analyses were undertaken using Cochran’s Q test and the MR-PRESSO global test. Results: Causal associations were found between diabetes and the nervous system in the hippocampus. Type 1 and type 2 diabetes were both identified as having adverse causal connections with the right hippocampal nervous system. This was supported by specific ranges of IVW-OR values (P < 0.05). The consistency of the sensitivity analyses further reinforced the main findings, revealing no significant heterogeneity or presence of horizontal pleiotropy. Conclusions: This study delved into the causal associations between diabetes and the hippocampal nervous system, revealing that both type 1 and type 2 diabetes have detrimental effects on the right hippocampal nervous system. Our findings have significant clinical implications as they indicate that diabetes may play a role in the decline of neurons in the right hippocampus among European populations, often resulting in cognitive decline.

KW - Causal effect

KW - Cognitive function

KW - Diabetes

KW - Hippocampus

KW - Mendelian randomization

KW - Nervous system

U2 - 10.1007/s12020-024-04081-y

DO - 10.1007/s12020-024-04081-y

M3 - Article

C2 - 39480567

AN - SCOPUS:85208069311

SN - 1355-008X

VL - 87

SP - 599

EP - 608

JO - Endocrine

JF - Endocrine

ER -