Effects of INSR genetic polymorphism on hippocampal volume and episodic memory in chinese type 2 diabetes

Abstract

We aimed to investigate the effect of the type 2 diabetes-specific insulin/IGF signaling genetic variants on the hippocampal volume and their relationships with episodic memory in Chinese patients with type 2 diabetes. Analysis of variance was used to evaluate the genotype-by-diagnosis interaction effect on hippocampal volume in Chinese participants (109 patients with type 2 diabetes, 116 healthy controls). Mediation analysis was performed to test whether the hippocampal volume would mediate the association between genotype and episodic memory in patients with type 2 diabetes. INSR (rs8101064) exhibited a significant genotype-by-diagnosis interaction effect on the bilateral hippocampal volumes (left, P = 0.020; right, P = 0.004, PFDR < 0.05). The T allele carriers exhibited smaller bilateral hippocampal volumes than the CC homozygotes in patients with type 2 diabetes (left, P = 0.004; right, P = 0.002). Mediation analysis revealed the significant mediation effect of the left hippocampal volume on the association between INSR (rs8101064) genetic polymorphism and the short- and long-term memory scores in patients with type 2 diabetes (short-term memory: 95% CI, −2.716, −0.266; long-term memory: 95% CI, −0.823, −0.103). Hyperglycemia exposure and INSR (rs8101064) genetic polymorphism had an interaction effect on the hippocampal volume, and the T allele of the INSR (rs8101064) may serve as a risk factor for the decreased hippocampal volume in Chinese patients with type 2 diabetes. The left hippocampal volume mediated the effect of INSR (rs8101064) genetic polymorphism on episodic memory in Chinese patients with type 2 diabetes, which provided a biological pathway for understanding how the INSR (rs8101064) genetic polymorphism affects episodic memory in type 2 diabetes.