Schneider ALC, et al. - The associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA_1c and diabetes duration) with brain volumes and vascular pathology on brain MRI were investigated. In addition, the researchers aimed to evaluate whether the relationships of diabetes with brain volumes were mediated by brain vascular pathology. More-severe diabetes (defined by higher HbA_1c and longer disease duration) was correlated with smaller brain volumes and an increased burden of brain vascular pathology, but not prediabetes or less-severe diabetes. They found no evidence that associations of diabetes with smaller brain volumes were mediated by brain vascular pathology, implying that other mechanisms could be responsible for these associations.

Methods

• The researchers performed this cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011–2013.
• They categorized participants by diabetes- HbA_1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA_1c ≥6.5%] <7.0% vs. ≥7.0%), with further stratification by diabetes duration (<10 vs. ≥10 years).

Results

• In adjusted analyses, participants with prediabetes and those with diabetes and HbA_1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05) compared with participants without diabetes and HbA_1c <5.7%.
• However, those with diabetes and HbA_1c ≥7.0% had smaller total brain volume (β -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016).
• Those with HbA_1c ≥7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA_1c <7.0% among participants with diabetes.
• Likewise, compared to those with a diabetes duration <10 years, participants with longer duration of diabetes (≥10 years) had smaller brain volumes and a higher burden of lacunes (all P< 0.05).
• As per the outcomes, the researchers found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).