Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Vascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Sci Rep. 2017 Jun 29;7(1):4382. doi: 10.1038/s41598-017-04515-w.
Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.
认知障碍在肾功能下降的人群中更为普遍。我们在一项横断面研究中检验了一个假设，即高同型半胱氨酸血症和/或脑小血管疾病（SVD）可能在 143 例无痴呆或既往卒中诊断的 2 型糖尿病患者中，介导肾脏和认知功能之间的联系。暴露和结局变量分别为估计肾小球滤过率（eGFR）和用改良的简易精神状态检查（3MS）评估的认知功能。候选中介物为血浆同型半胱氨酸浓度以及磁共振成像显示的脑小血管疾病，包括脑梗死、脑微出血、脑室周围高信号、深部和皮质下白质高信号。在调整了 12 个潜在混杂因素的多元回归模型中，eGFR 与 3MS 评分呈正相关，与同型半胱氨酸呈负相关，但与任何类型的 SVD 均无显著相关性。当将每种 SVD 添加到模型中时，eGFR 与 3MS 的关联仍然显著，而当用同型半胱氨酸替代 SVD 时，这种关联则消失。中介分析表明，同型半胱氨酸存在显著的中介作用（P=0.062），但 SVD 无明显的中介作用（P=0.842-0.930）。因此，在 2 型糖尿病患者中，同型半胱氨酸而非 SVD 可能是肾脏和认知功能之间的中介。
