OBJECTIVE To study to what extent differences in cognitive performance between individuals with different glucose metabolism status are potentially attributable to hyperglycemia, insulin resistance, and blood pressure–related variables.

RESEARCH DESIGN AND METHODS We used cross-sectional data from 2,531 participants from the Maastricht Study (mean age ± SD, 60 ± 8 years; 52% men; n = 666 with type 2 diabetes), all of whom completed a neuropsychological test battery. Hyperglycemia was assessed by a composite index of fasting glucose, postload glucose, glycated hemoglobin (HbA_1c), and tissue advanced glycation end products; insulin resistance by the HOMA of insulin resistance index; and blood pressure–related variables included 24-h ambulatory pressures, their weighted SDs, and the use of antihypertensive medication. Linear regression analyses were used to estimate mediating effects.

RESULTS After adjustment for age, sex, and education, individuals with type 2 diabetes, compared with those with normal glucose metabolism, performed worse in all cognitive domains (mean differences in composite z scores for memory −0.087, processing speed −0.196, executive function and attention −0.182; P values <0.032), whereas individuals with prediabetes did not. Diabetes-associated differences in processing speed and executive function and attention were largely explained by hyperglycemia (mediating effect 79.6% [bootstrapped 95% CI 36.6; 123.4] and 50.3% [0.6; 101.2], respectively) and, for processing speed, to a lesser extent by blood pressure–related variables (17.7% [5.6; 30.1]), but not by insulin resistance. None of the factors explained the differences in memory function.

CONCLUSIONS Our cross-sectional data suggest that early glycemic and blood pressure control, perhaps even in the prediabetic stage, may be promising therapeutic targets for the prevention of diabetes-associated decrements in cognitive performance.

目的研究具有不同糖代谢状态的个体之间认知能力的差异在多大程度上可归因于高血糖症，胰岛素抵抗和与血压相关的变量。

研究设计和方法我们使用了来自马斯特里赫特研究的2531名参与者的横断面数据（平均年龄±SD，60±8岁； 52％的男性；n = 666患有2型糖尿病），所有这些人均完成了神经心理学测试。通过空腹血糖，后负荷葡萄糖，糖化血红蛋白（HbA _1c）和组织晚期糖基化终产物的综合指数评估高血糖。胰岛素抵抗通过HOMA的胰岛素抵抗指数；与血压相关的变量包括24小时动态血压，其加权SD以及使用降压药的情况。线性回归分析用于估计中介作用。

结果经过年龄，性别和教育程度的调整后，与2型糖尿病患者相比，糖代谢正常的人在所有认知领域的表现均较差（记忆z综合得分-0.087，处理速度-0.196，执行功能的均值差异和注意−0.182; P值<0.032），而患有糖尿病的人则没有。糖尿病相关的处理速度，执行功能和注意力的差异在很大程度上由高血糖症引起（介导作用为79.6％[自举95％CI 36.6; 123.4]和50.3％[0.6; 101.2]），并且对于处理速度而言，血压相关变量的影响较小（17.7％[5.6; 30.1]），而非胰岛素抵抗。没有任何因素可以解释记忆功能的差异。

结论我们的横断面数据表明，即使在糖尿病前期阶段，早期的血糖控制和血压控制也可能成为预防糖尿病相关的认知功能下降的有希望的治疗靶标。