Abstract
Background: Insulin-like growth factor (IGF)-1, through insulin/IGF-1
signaling pathway, is involved in the pathogenesis of type 2 diabetes mellitus (T2DM) and
Alzheimer’s disease.
Objective: This study aimed to assess the association of serum IGF-1 and IGF
binding protein (IGFBP)-3 levels with cognition status and to determine whether IGF-1
rs972936 polymorphism is associated with T2DM with mild cognitive impairment (MCI).
Methods: A total of 150 T2DM patients, 75 satisfying the MCI diagnostic
criteria and 75 exhibiting healthy cognition, were enrolled in this study. The cognitive
function of the subjects was extensively assessed. Serum IGF-1 and IGFBP-3 levels were
measured through enzyme-linked immunosorbent assay; IGF-1/IGFBP-3 molar ratio was
calculated. Single nucleotide polymorphisms of the IGF-1-(rs972936) gene were
analyzed.
Results: Serum IGF-1/IGFBP-3 molar ratio in MCI patients was significantly
lower than that in the control group (p = 0.003). Significant negative
correlations were found between IGF-1/IGFBP-3 molar ratio and Trail Making Test A and B
(TMT-A and TMT-B) scores (p = 0.003; p < 0.001,
respectively), which indicated executive function. Further multiple step-wise regression
analysis revealed that the TMT-A or TMT-B score was significantly associated only with
serum IGF-1/IGFBP-3 molar ratio (p = 0.016; p <
0.001, respectively). No significant difference was found in the genotype or allele
distribution of IGF-1 rs972936 polymorphism between MCI and control groups.
Conclusions: A low serum IGF-1/IGFBP-3 molar ratio is associated with the
pathogenesis of MCI, particularly executive function in T2DM populations. Further
investigation with a large population size should be conducted to confirm this observed
association.
