第一临床医学院知识库

目的：本研究采用DKI及¹H-MRS技术，对T2DM患者的脑微结构损害、代谢情况进行初步探究，探讨DKI、¹H-MRS参数值与患者基本临床指标、MoCA评分之间的相关性,以助探究T2DM患者认知功能障碍可能的病理生理机制，并提供影像学评价依据，也对DKI、¹H-MRS联合应用于T2DM患者伴认知功能障碍的价值进行评价。

材料和方法：挑选兰大一院2017年3月至2018年1月期间符合入组标准的T2DM住院患者42人，进行MoCA量表评分，将其分为A组（T2DM-MCI组）和B组（T2DM-NMCI组），A组为T2DM患伴有认知功能障碍组（21分≤评分＜26分），其中男性6位，女性9位；B组为T2DM患者不伴认知功能障碍组（评分≥26分），男性11位，女性16位；另设健康对照C组（HC组）20位，男性10位，女性10位。采集上述入选对象的基础临床指标及生化实验室指标，包括年龄、性别、受教育程度、身高、体重、BMI、病程、血脂（TG、TC、LDL、HDL）。同时对上述入选对象行常规核磁序列扫描及¹H-MRS、DKI扫描。对临床基础指标、检验指标及MoCA评分进行差异性分析，性别为计数资料采用卡方检验分析，其余均为计量资料采用单因素方差分析，p<0.05时，差异具有统计学意义。三组间双侧额叶DKI参数值、¹H-MRS代谢物含量及其比值差异性比较采用单因素方差分析，p<0.05时，再进行两组间多重比较，采用最小差异性检验（LSD-t）。另外，采用spearman偏相关分析法对双侧额叶DKI参数值、¹H-MRS代谢物含量及其比值与临床基础指标、检验指标、MoCA评分进行相关性分析，求出相关系数r和并报告假设检验结果，当p<0.05时，组间差异具有统计学意义。

结果：1.¹H-MRS代谢物含量统计分析结果：T2DM-MCI、T2DM-NMCI组与HC组相比，双侧额叶NAA、Cr、Cho、Glx含量减低，而mI含量增加，差异具有统计学意义（p＜0.05）。¹H-MRS代谢物比值统计学分析结果：T2DM-MCI、T2DM-NMCI组较HC组相比，双侧额叶Cho/Cr、Glx/Cr减低，m I/Cr升高，差异具有统计学意义（p＜0.05）。¹H-MRS代谢物含量、比值与临床指标、MoCA评分相关分析发现，左侧额叶NAA、Cho、Cr、Cho/Cr、Glx/Cr及右侧额叶NAA、NAA/Cr、Glx/Cr与病程呈负相关，左侧额叶mI/Cr及右侧额叶mI、mI/Cr与病程呈正相关；左侧额叶Cho、Glx、NAA/Cr及右侧额叶NAA、Cho、Glx、Cho/Cr与BMI呈负相关，左侧额叶mI/Cr及右侧额叶mI、mI/Cr与BMI呈正相关；双侧额叶NAA、Cho、Glx、Cho/Cr、Glx/Cr及左侧额叶Cr与HbA1c呈负相关，双侧额叶mI、mI/Cr与HbA1c呈正相关；双侧额叶mI、mI/Cr与MoCA评分呈负相关，双侧额叶Cho、Cho/Cr、Glx/Cr及右侧额叶Glx与MoCA评分呈正相关；双侧额叶Cho、Glx、Cho/Cr、Glx/Cr与空腹血糖呈负相关，双侧额叶mI、mI/Cr与空腹血糖呈正相关；左侧额叶Cho及右侧额叶Cho、Glx、Glx/Cr与甘油三酯呈负相关，左侧额叶mI、mI/Cr与甘油三脂呈正相关。2.T2DM-MCI、T2DM-MCI较HC组相比，双侧额叶MK、FA逐渐减低，MD值逐渐升高，差异具有统计学意义（p＜0.05）。相关分析发现，双侧额叶MK、FA与病程呈负相关，双侧额叶MD与病程呈负相关；右侧额叶MD与BMI呈正相关；左侧额叶MK、FA与BMI呈负相关；双侧额叶MD与HbA1c呈正相关，左侧额叶MK、FA及右侧额叶MK与HbA1c呈负相关；双侧额叶MK、FA与MoCA评分呈正相关；右侧额叶MD与空腹血糖呈正相关，双侧额叶FA与空腹血糖呈负相关；右侧额叶MD与甘油三脂呈正相关，右侧额叶FA与甘油三酯呈负相关。

结论：1.应用¹H-MRS技术采集入选对象代谢物含量、比值，可以初略反应T2DM伴认知功能障碍患者双侧额叶代谢紊乱情况及其变化规律；T2DM患者双侧额叶出现NAA、Cr、Glx、Cho/Cr、Glx/Cr减低，mI、mI/Cr升高，提示T2DM存在能量代谢紊乱。上述部分参数指标有望成为评估T2DM-MCI患者的生物学指标。 2.MK、FA、MD的变化规律证实T2DM患者双侧额叶存在脑实质微细结构损害并能反应其损害严重程度。3.研究结果显示T2DM患者脑微结构损伤、代谢紊乱的DKI、¹H-MRS参数指标与T2DM患者病程、BMI、空腹血糖、HbA1c及MoCA评分具有相关性。这对预测与诊断T2DM患者早期认知损伤起着非常重要的作用。4.DKI联合MRS技术能够准确反映T2DM脑微结构损害、代谢紊乱，对T2DM脑损害做出早期诊断并对评估损害程度，利于我们对T2DM脑损害进行早期干预、早期治疗，对患者预后和病情进展有积极意义。

Objective: In the 20th century, the aging degree of the society is becoming more and more serious, and the incidence of T2DM is getting higher and higher, and the cognitive dysfunction caused by it is attracting more and more attention.This research adopts the DKI and ¹H- MRS technology, damage to the brain in patients with T2DM microstructure, metabolic disorder situation carries on the preliminary exploration, DKI, ¹H- MRS parameter values and basic clinical index, the correlation between cognitive function score.To help explore the pathophysiology of cognitive dysfunction in patients with T2DM may, and provide imaging evaluation basis, also to DKI, ¹H-MRS jointly applied in T2DM patients to evaluate the value of the associated with cognitive dysfunction.

Materials and methods: Pick the first hospital of lanzhou university during March 2017 to January 2018, comply with the standard set of 42 people hospitalized patients with type 2 diabetes, mental state of patients according to the score of MoCA scale, it can be divided into group A (T2DM-MCI group) and group B (T2DM-NMCI group), A group for T2DM with cognitive dysfunction (21 points≤MoCA score<26 points), including six male, and nine female;In group B, patients with T2DM were not associated with cognitive dysfunction (score>26points), male 11 and female 16;There were 20 healthy control groups (HC group), 10 males and 10 females.Acquisition of the selected objects based on clinical and biochemical laboratory indicators, including age, gender, level of education, height, weight, BMI, course duration (diabetes), blood lipid (TG, TC, LDL, HDL), at the same time for the selected object routine MRI scan sequence and ¹H-MRS, DKI scanning.DKI and MRS parameters were measured by symmetry, and the lateral prefrontal cortex was the ROI, and the same anatomical level was selected as far as possible (the baseline was the largest level in the anterior horn of bilateral ventricle).Basis for clinical index, index test and MoCA score difference analysis, the gender for count data by chi-square analysis, the rest are measurement data using single factor analysis of variance, p<0.05, the difference is statistically significant.Between the three groups of bilateral frontal lobe DKI parameter values, ¹H-MRS metabolites and ratio difference comparison using single factor analysis of variance, p<0.05, and then to multiple comparison between the two groups, with minimum difference (LSD) test.In addition, by spearman correlation analysis of bilateral frontal lobe DKI parameter values, and ¹H-MRS metabolites content ratio based indicators, test indicators, MoCA score and clinical correlation analysis, and the correlation coefficient r and hypothesis testing and report as a result, when p<0.05, statistically significant difference between the groups.

Results:1.From the ¹H-MRS metabolites content results showed that T2DM-MCI, T2DM-NMCI group compared with HC group, bilateral frontal lobes, Cho, NAA, Cr that Glx content is reduced, and mI content increase, the difference is statistically significant (p<0.05);From the results of the ratio of ¹H-MRS metabolites, it can be seen that compared with HC group in T2DM-MCI and T2DM-NMCI group, there was a decrease in the bilateral upper lobe Cho/Cr, Glx/Cr, and increased mI/Cr, and the difference was statistically significant (p<0.05).The correlation analysis found that the left frontal lobe NAA, Cho, Cr, Cho/Cr, Glx/Cr and the right frontal lobes NAA, NAA/Cr, Glx/Cr were negatively correlated with the course of the disease, and the left frontal lobe mI/Cr and the right frontal lobe mI, mI/Cr were positively correlated with the course of the disease.The left frontal lobe Cho, Glx, NAA/Cr and the right frontal lobe NAA, Cho, Glx, Cho/Cr were negatively correlated with BMI, and the left frontal lobe mI/Cr and the right frontal lobe mI, mI/Cr were positively correlated with BMI.Bilateral frontal lobes NAA, Cho, Glx, Cho/Cr, Glx/Cr and left frontal lobe Cr were negatively correlated with HbA1c, and the bilateral frontal lobe mI, mI/Cr and HbA1c were positively correlated.Bilateral frontal lobe mI, mI/Cr and MoCA score were negatively correlated, and bilateral frontal lobe Cho, Cho/Cr, Glx/Cr and right frontal lobe Glx were positively correlated with MoCA score.Bilateral frontal lobe Cho, Glx, Cho/Cr, Glx/Cr were negatively correlated with fasting blood glucose, and bilateral frontal lobe mI, mI/Cr and fasting blood glucose were positively correlated.The left frontal lobe Cho and the right frontal lobe Cho, Glx, Glx/Cr were negatively correlated with triglyceride, and the left frontal lobe mI, mI/Cr was positively correlated with triglyceride.2. Compared with HC group, T2DM-MCI and T2DM-MCI were gradually reduced in both lateral lobe MK and FA, and MD was gradually increased, and the difference was statistically significant (p<0.05).The correlation analysis found that the bilateral frontal lobe MK, FA and the course of disease were negatively correlated, and the bilateral frontal lobe MD was negatively correlated with the course of disease.The right frontal lobe MD was positively correlated with BMI.The left frontal lobe MK, FA and BMI were negatively correlated.Bilateral frontal lobe MD was positively correlated with HbA1c, and the left frontal lobe MK, FA and right frontal lobe MK were negatively correlated with HbA1c.The bilateral frontal lobe MK and FA were positively correlated with MoCA scores.The right frontal lobe was positively correlated with fasting blood glucose, and bilateral frontal FA was negatively correlated with fasting blood glucose.The right frontal lobe was positively correlated with triglyceride, and the right frontal lobe was negatively correlated with triglyceride.

Conclusion:Selection of bilateral frontal lobe for ROI, the 1.application of ¹H-MRS technology acquisition selected object data and calculate the ratio of metabolites, these parameters are just at the beginning of reaction T2DM patients with cognitive dysfunction with bilateral frontal metabolic disorder situation and its change rule;In patients with T2DM, the content of NAA, Cr and Glx decreased in bilateral frontal lobes, while Cho/Cr, Glx/Cr decreased, mI content increased, and mI/Cr increased, suggesting that T2DM had an energy metabolism disorder.These parameters are expected to be the biological indicators for the assessment of patients with T2DM-MCI.2.MK, FA, MD, confirmed that the change rule of T2DM patients with bilateral frontal micro-structure parenchymal damage and can response to the damage severity, infer micro-structure T2DM patients with brain injury may be the pathophysiological mechanism.3.The results showed that the DKI and 1h-mrs parameters of T2DM patients were correlated with the pathogenesis, BMI, fasting blood glucose, HbA1c and MoCA scores of T2DM patients.This plays a very important role in predicting and diagnosing early cognitive impairment in T2DM patients, and also provides effective measures for intervention of cognitive dysfunction in T2DM patients.4.Joint MRS and DKI technology can accurately reflect T2DM brain microstructure damage, metabolic disorders, to make early diagnosis of T2DM brain injury and to assess the damage, for our early intervention, early treatment of T2DM brain damage, is important for prognosis and disease progression in patients with positive significance.