Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.
Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.
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DOI：
10.1038/s41598-017-04515-w
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发表时间：
2017-06-29
影响因子：
4.6
通讯作者：
Inaba M
中科院分区：
文献类型：
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作者：
Sonoda M;Shoji T;Kuwamura Y;Okute Y;Naganuma T;Shima H;Motoyama K;Morioka T;Mori K;Fukumoto S;Shioi A;Shimono T;Fujii H;Kabata D;Shintani A;Emoto M;Inaba M
认知障碍在肾功能下降的患者中更为普遍。在一项横断面研究中，我们对143例未诊断为痴呆或既往卒中的2型糖尿病患者进行了假设检验，即同型半胱氨酸升高和/或脑小血管疾病（SVDs）介导了肾脏和认知功能之间的联系。暴露和结果变量分别为估计的肾小球滤过率（eGFR）和采用改良简易精神状态（3 MS）检查评价的认知能力。候选介质为血浆同型半胱氨酸浓度和SVD，包括无症状性脑梗死、脑微出血、脑室周围高信号、深部和皮质下白色物质高信号（通过磁共振成像）。在校正了12个潜在混杂因素的多元回归模型中，eGFR与3 MS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均无显著性相关。当将每种SVD加入模型时，eGFR与3 MS的相关性仍然显著，而当用同型半胱氨酸代替SVD时，eGFR与3 MS的相关性消失。中介作用分析显示同型半胱氨酸几乎具有显著的中介作用（P = 0.062），但SVDs没有显著的中介作用（P = 0.842-0.930）。因此，同型半胱氨酸，而不是SVDs，被证明是2型糖尿病患者肾脏和认知功能之间的可能介质。
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.