1. Association Between Plasma LRG1 and Lower Cognitive Function in Asians With Type 2 Diabetes Mellitus.
- Author
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Low S, Moh A, Pandian B, Tan XL, Pek S, Zheng H, Ang K, Tang WE, Lim Z, Subramaniam T, Sum CF, and Lim SC
- Subjects
- Humans, Female, Middle Aged, Male, Aged, Asian People genetics, Cognitive Dysfunction blood, Cognitive Dysfunction genetics, Cognitive Dysfunction etiology, Vascular Stiffness physiology, Mendelian Randomization Analysis, Follow-Up Studies, Pulse Wave Analysis, Longitudinal Studies, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 psychology, Diabetes Mellitus, Type 2 complications, Cognition physiology, Polymorphism, Single Nucleotide, Glycoproteins blood, Glycoproteins genetics
- Abstract
Context: Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear., Objective: Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian randomization (MR) and the role of arterial stiffness as a potential mediator., Methods: T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism. Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function., Results: Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients -1.38 (95% CI -2.55 to -.21; P = .021) and -1.38 (95% CI -2.70 to -.07; P = .039), respectively. Genetically predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient -7.44 (95% CI -14.14 to -.74; P = .030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score., Conclusion: Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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