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

Livny, A., Ravona-Springer, R., Heymann, A., Priess, R., Kushnir, T., Tsarfaty, G., Rabinov, L., Moran, R., Hoffman, H., Cooper, I., Greenbaum, L., Silverman, J., Sano, M., Johnson, S. C., Bendlin, B. B., & Schnaider Beeri, M.

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


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.


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