The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus

Abstract

Backgrounds and Aims. Insulin-induced gene 2 (INSIG-2) is closely related to hypercholesteremia, which is a well-recognized risk factor of mild cognitive impairment (MCI) in type 2 diabetes mellitus (T2DM). We aim to investigate the association between promoter of the INSIG-2 rs7566605 single-nucleotide polymorphism (SNP) and T2DM with MCI. Methods. 233 T2DM patients with MCI or without MCI were recruited. Baseline data and genotype frequency were compared between MCI and non-MCI groups. Demographic parameters and neuropsychological tests results were analyzed among patients with different genotypes. Further correlation and regression analysis were conducted to find the association between cognition and cholesterol. Results. Despite no significant statistical difference was detected, we observed higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) in patients with MCI than those without MCI. In addition, we observed higher TC and LDL levels in patients with GG or GC genotypes than those with CC genotype (P<0.001, P=0.004, or P<0.001, P=0.002). Interestingly, increased MoCA and decreased TMTB scores were found in patients with CC genotype, compared to those with GG or CG genotype (P=0.009, P=0.024, or P=0.005, P=0.109). Moreover, partial correlation (P=0.030 and P=0.004, respectively) and multiple linear regression (P=0.030 and P=0.005, respectively) showed that TC and LDL levels are associated with the TMTB score, indicating the executive function. Conclusions. CC genotype of INSIG-2 rs7566605 may be a protective factor of hypercholesteremia susceptible to MCI, especially to the executive function of T2DM. This trial is registered with ChiCTROCC15006060.

Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus

“…LDL-C level was positively associated with execution function in patients with hypercholesteremia. Similarly, our latest results show that hypercholesteremia, especially increased LDL-C may influence the executive function of patients with T2DM [ 49 ]. Additionally, Xia et al demonstrated the disordered functional connectivity of bilateral hippocampus-middle frontal gyrus in diabetic patients with poorly controlled LDL-C, and associated with executive function [ 13 ].…”

CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing

“…However, functional distinctions may exist between INSIG1 and INSIG2 in that they are differentially regulated by metabolic hormone and metabolites [ 52 , 53 ]. Several studies have found that INSIG2 genetic polymorphisms are associated with the metabolic syndrome [ [53] , [54] , [55] ], while the common variation in INSIG1 is unlikely to have a major effect on type 2 diabetes and obesity risk [ 56 ]. Further understanding of the regulatory and functional differences between INSIG1 and INSIG2 may provide a new way to explain the preferential interaction between CD36 and INSIG2.…”

Free Triiodothyronine Levels are Related to Executive Function and Scene Memory in Type 2 Diabetes Mellitus Patients Without Diagnosed Thyroid Diseases

“…In our previous study, we found higher HbA1c level, in T2DM patients with MCI than these without MCI. 51 , 52 These factors may limit the accuracy of results as confounding factors for a cross-section study. So, in the later analysis, these factors were corrected.…”