Association between Visit-to-Visit Glucose Variability and Cognitive Function in Aged Type 2 Diabetic Patients: A Cross-Sectional Study

PLoS One. 2015 Jul 1;10(7):e0132118. doi: 10.1371/journal.pone.0132118. eCollection 2015.


Background and purpose: Diabetes is associated with cognitive decline as well as the development of dementia. Although mean blood glucose levels are typically used to assess the status of diabetic patients, glucose variability is also involved in the manifestation of macro- and microvascular complications in this population. Thus, the present study sought to determine whether visit-to-visit glucose variability contributes to cognitive decline in patients with type 2 diabetes.

Methods: The present study assessed 68 patients with type 2 diabetes using several validated neuropsychological measures. All patients had no cerebrovascular disease, history of hypoglycemia, psychiatric conditions, or other medical illnesses. Standard deviations (SDs) and coefficients of variance (CVs) of the patients' blood glucose (after fasting and 2 hours postprandial; FBS and PP2), and glycated hemoglobin (HbA1c) values were used as indices of glucose variability. The cognitive outcome parameters were transformed with z-scores and entered into a multiple linear regression model that included educational status, age, sex, vascular risk factors, and mean glucose parameters as covariates.

Results: The mean age of the total patient population was 70.9 years; 46 (67.6%) of the patients were men, and the median follow-up duration at our endocrinology outpatient clinic was 4.8 years. The mean FBS and PP2 glucose levels of the patients were 132 mg/dL and 199 mg/dL, respectively, and the mean HbA1c level was 8.0%. A univariable analysis revealed that only the PP2 value was associated with the Mini-Mental State Examination (MMSE) score, and multivariable analysis revealed that a high SD and/or CV for PP2 glucose were associated with low scores on the Rey Complex Figure Copy test and/or the Verbal Learning Test. Additionally, a high SD and a higher CV for HbA1c level were significantly associated with low MMSE and Digit Span test scores even after adjusting for mean HbA1c values.

Conclusions: The present data indicate that a greater degree of visit-to-visit glucose variability influenced specific types of cognitive function in type 2 diabetic patients independently of mean blood glucose levels. Future studies should focus on whether reductions in glycemic variability will improve the cognitive decline observed in type 2 diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis*
  • Cognition Disorders / blood*
  • Cognition Disorders / epidemiology
  • Comorbidity
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / psychology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypertension / blood
  • Hypertension / epidemiology
  • Hypertension / psychology
  • Linear Models
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Sampling Studies
  • Single-Blind Method
  • Smoking / blood
  • Smoking / epidemiology
  • Smoking / psychology


  • Blood Glucose
  • Glycated Hemoglobin A

Grant support

This study was supported by a grant from the Korea Drug Company, limited (2012-50), and by Hallym University Specialization Fund (HRF-S-51). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.