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

OBJECTIVEWe assessed whether the apolipoprotein epsilon 4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA(1c) SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSWMH 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.RESULTSHbA(1c) variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA(1c), 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).CONCLUSIONSThe 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.