title: Decreased Serum IGF-1/IGFBP-3 Molar Ratio is Associated with Executive Function Behaviors in Type 2 Diabetic Patients with Mild Cognitive Impairment.
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.
authors.affiliation: Medical School of Southeast University, Nanjing, PR China; Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Medical School of Southeast University, Nanjing, PR China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Medical School of Southeast University, Nanjing, PR China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xia
authors.affiliation: Medical School of Southeast University, Nanjing, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Cai
authors.affiliation: Medical School of Southeast University, Nanjing, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Sun
authors.affiliation: Medical School of Southeast University, Nanjing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
mesh_terms: D000368:Aged; D060825:Cognitive Dysfunction / Q000097:blood* / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
keywords: Insulin-like growth factor-1; mild cognitive impairment; polymorphism; type 2 diabetes mellitus