Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients

Oncotarget. 2017 Feb 28;8(9):15126-15135. doi: 10.18632/oncotarget.14852.


Background and aims: People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients.

Results: In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghrelin levels compared with their healthy-cognition subjects (all p < 0.05). Further logistic regression analysis showed that ghrelin level was one of independent factors for MCI in T2DM patients (p < 0.05). Moreover, partial correlation analysis demonstrated that ghrelin levels were positively associated with the scores of Montreal Cognitive Assessment (r = 0.196, p = 0.041) and Auditory Verbal Learning Test-delayed recall (r = 0.197, p = 0.040) after adjustment for HbA1c, FBG and HOMA-IR, wherein the latter represented episodic memory functions. No significant differences were found for the distributions of genotype and allele of ghrelin rs4684677 polymorphism between MCI and control group.

Materials and methods: A total of 218 T2DM patients, with 112 patients who satisfied the MCI diagnostic criteria and 106 who exhibited healthy cognition, were enrolled in this study. Demographic characteristics, clinical variables and cognitive performances were extensively assessed. Plasma ghrelin levels and ghrelin rs4684677 polymorphism were also determined.

Conclusions: Our results suggest that decreased ghrelin levels are associated with MCI, especially with episodic memory dysfunction in T2DM populations.

Keywords: ghrelin; mild cognitive impairment; polymorphism; type 2 diabetes mellitus.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis*
  • Case-Control Studies
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / etiology
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Follow-Up Studies
  • Genotype
  • Ghrelin / blood*
  • Ghrelin / genetics*
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prognosis


  • Biomarkers
  • Ghrelin
  • Glycated Hemoglobin A