OBJECTIVE To examine 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 and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.

RESEARCH DESIGN AND METHODS 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. Participants were categorized 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, compared with participants without diabetes and HbA_1c <5.7%, 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), but 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). Among participants with diabetes, 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%. Similarly, participants with longer duration of diabetes (≥10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).

CONCLUSIONS More-severe diabetes (defined by higher HbA_1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

目的在脑MRI上检查糖尿病前期，糖尿病和糖尿病严重程度（通过HbA _1c和糖尿病持续时间评估）与脑容量和血管病理的关系，并评估糖尿病与脑容量的关系是否由脑血管病理学介导。

研究设计与方法对2011年进行了3T脑MRI扫描的1,713名社区动脉粥样硬化风险参与者的横断面研究神经认知研究（平均年龄75岁，女性60％，黑人27％，糖尿病前期糖尿病，35％糖尿病） –2013年。参加者通过糖尿病-HBA归类_1C状态（<5.7％[参考]），为无糖尿病，糖尿病前期（5.7到<6.5％），和与糖尿病（[定义为现有诊断或HBA _1C ≥6.5％] <7.0％ vs.≥7.0％），并根据糖尿病病程进一步分层（<10 vs.≥10年）。

结果在校正后的分析中，与没有糖尿病且HbA _1c <5.7％的参与者相比，患有糖尿病前期者和糖尿病且HbA _1c <7.0％的参与者的脑容量或血管病理没有显着差异（所有P > 0.05），糖尿病和HBA _1C ≥7.0％具有较小的总脑容量（β-0.20 SDS，95％CI -0.31，-0.09），更小的区域的脑体积（包括额叶，颞，枕，和顶叶;深灰质;阿尔茨海默病签名区；海马区[所有P <0.05]），并增加了白质高信号（WMH）的负担（P = 0.016）。在患有糖尿病的参与者中，患有HbA _1c的参与者与HbA _1c <7.0％的患者相比，≥7.0％的患者的总和区域大脑体积较小，WMH的负担增加（所有P <0.05）。同样，与糖尿病持续时间＜10年的受试者相比，糖尿病持续时间较长（≥10年）的受试者脑容量较小，腔内负担更高（所有P <0.05）。通过结构方程模型，我们没有发现WMH介导的糖尿病与较小脑容量相关联的调解证据（所有P > 0.05）。

结论严重程度更高的糖尿病（由较高的HbA _1c和更长的疾病持续时间定义）而不是糖尿病前期或程度较轻的糖尿病与较小的脑容量和增加的脑血管病理学负担相关。没有证据表明糖尿病与较小脑容量的关联是由脑血管病理学介导的，这表明其他机制可能是造成这些关联的原因。