Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes

Diabetes Care. 2016 Jun;39(6):1056-9. doi: 10.2337/dc15-2331. Epub 2016 Apr 8.

Abstract

Objective: We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D).

Research design and methods: WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles.

Results: HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050).

Conclusions: The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.

MeSH terms

  • Aged
  • Alleles
  • Apolipoprotein E4 / genetics*
  • Blood Glucose / metabolism*
  • Cardiovascular Diseases
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Genotype
  • Glycated Hemoglobin / metabolism*
  • Heterozygote
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Risk Factors
  • White Matter / diagnostic imaging*
  • White Matter / pathology

Substances

  • Apolipoprotein E4
  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human