糖调节受损及转甲状腺素蛋白与脑小血管病患者脑白质病变的相关性

Association of impaired glucose regulation and transthyretin with white matter hyperintensity in cerebral small-vessel disease patients

目的探讨糖调节受损及转甲状腺素蛋白(transthyretin,TTR)与脑小血管病患者脑白质高信号(white matter hyperintensity,WMH)的相关性。方法连续入选2020年7月至2022年6月华北理工大学附属医院神经内科住院的非糖尿病脑小血管病患者450例,根据WMH诊断标准分为WMH组304例和非WMH组146例,其中WMH组依据Fazekas评分进一步分为轻度组180例,中度组61例,重度组63例。采用口服葡萄糖耐量试验评定糖调节受损患病情况,并采用双抗体夹心法测定TTR水平,分析并对比各项指标。结果WMH组糖调节受损比例明显高于非WMH组(79.3%vs 68.5%,P=0.012),TTR水平明显低于非WMH组[(271.91±35.63)mg/L vs(282.25±47.04)mg/L,P=0.020]。所有患者血清TTR水平四分位组分分析显示,血清TTR水平与脑小血管病患者WMH患病情况呈线性负相关(r=-0.154,P=0.046)。多因素logistic回归分析显示,矫正年龄、高血压、同型半胱氨酸的影响,排除其他混杂因素后,糖调节受损、TTR仍与脑小血管病患者WMH相关(OR=1.822,95%CI:1.145~2.902,P=0.011;OR=0.994,95%CI:0.989~0.999,P=0.013)。轻度组糖调节受损比例明显低于重度组,差异有统计学意义(P<0.01)。与轻度组比较,中度组和重度组TTR水平明显降低,差异有统计学意义(P<0.05);与中度组比较,重度组TTR水平明显降低,差异有统计学意义(P<0.05)。脑小血管病患者WMH与空腹血糖受损、糖耐量减低呈正相关(r=0.223,P=0.012;r=0.307,P=0.001),与TTR水平呈负相关(r=-0.235,P=0.001)。结论糖调节受损及TTR与脑小血管病患者WMH的发生及严重程度相关。

Objective To investigate the association of impaired glucose regulation and transthyretin(TTR)with white matter hyperintensity(WMH)in cerebral small-vessel disease(CSVD)patients.Methods A total of 450 CSVD patients with non-diabetes hospitalized in the Department of Neurology of the Affiliated Hospital of North China University of Science and Technology from July 2020 to June 2022 were consecutively enrolled.According to the diagnostic criteria of WMH,they were divided into WMH group(n=304)and non-WMH group(n=146).The WMH group was further assigned into mild(n=180),moderate(n=61)and severe WMH subgroups(n=63)based on their Fazekas score.The prevalence of impaired glucose regulation(IGR)was assessed by OGTT test,and the level of TTR was measured by double antibody sandwich method,and various indexes were analyzed and compared.Results The proportion of IGR patients was significantly higher(79.3%vs 68.5%,P=0.012),and the TTR level was obviously decreased(271.91±35.63 mg/L vs 282.25±47.04 mg/L,P=0.020)in the WMH group than the non-WMH group.The results of quartile serum TTR level analysis indicated that the serum TTR level was linearly negatively correlated with the prevalence of WMH in CSVD patients(r=-0.154,P=0.046).Multivariate logistic regression analysis showed that IGR and TTR were still associated with WMH,after correction of age,hypertension and homocysteine and exclusion of other confounding factors(OR=1.822,95%CI:1.145-2.902,P=0.011;OR=0.994,95%CI:0.989-0.999,P=0.013).The mild WMH subgroup had lower ratio of IGR than the severe WMH subgroup(P<0.01)in CSVD patients.The TTR level was obviously lower in the moderate and severe WMH subgroups than the mild WMH subgroup(P<0.01),and in the severe WMH subgroup than the moderate WMH subgroup(P<0.05).WMH in the CSVD patients was positively correlated with impaired fasting glucose and impaired glucose tolerance(r=0.223,P=0.012;r=0.307,P=0.001),and negatively correlated with TTR level(r=-0.235,P=0.001).ConclusionIGR and TTR are related to the occurrence and severity of WMH in CSVD patients.