More than 20.4% of the elderly population have diabetes in china, among which Type 2 Diabetes Mellitus (T2DM) accounts for 90%^[1]. T2DM is a major risk factor for cardiovascular disease and has been consistently associated with an increased risk of incident dementia, as well as with cognitive deficits and increased brain atrophy^[2-4]. T2DM related cognitive decline may be partly due to neuroanatomical alterations revealed by structural MR. Diffusion tensor imaging (DTI) has been used to quantify microstructural alterations in white matter that may also impact cognition^[5]. Fractional anisotropy (FA) and average diffusion coefficient( DCavg ) value derived from DTI reflect verall white matter health, maturation, and organization^[6].Voxel-based morphometry (VBM), which reflects brain volume, can be used in early detecting brain structural abnormalities in T2DM patients.

Our research aims to detect brain microstructure changes in T2DM patients both in white matter (WM) and grey matter (GM) based on global DTI and VBM.

This prospective single-center study was approved by the local Ethics Committee and informed consent was obtained. 16 T2DM (9 men, 7 women; mean age, 54 years; range, 34-69 years) and 15 control subjects (6 men, 9 women; mean age, 48 years; range, 37-64 years) were recruited in this study with inclusion standard as follows: T2DM criteria according to the 1999 World Health Organization diagnostic criteria ^[7]. Controls: Individuals with normal HbA1c and blood glucose level and no evidence of T2DM. Exclusion:1) Type 1 diabetes mellitus and secondary diabetes mellitus. 2) History of major neurological diseases, cerebrovascular accidents, psychiatric or serious cardiovascular disease. 3) Cognitive complaints that cause impairment in social or occupational functioning.

Each subject underwent conventional MRI, DTI and structure MRI on a 3.0-T MRI system (MR750, GE Healthcare, Milwaukee, USA). Conventional brain T1-weighted (T1W), T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images be obtained to exclude serious brain diseases. Following the scan, an axial 3D brain volume imaging (3D-BRAVO) was acquired according to the following parameters: echo time (TE)=3.2 ms, repetition time (TR)=8.2 ms, inversion time (TI)=450 ms, flip angle (FA)=12°, matrix size= 256 × 256, FOV= 24 cm × 24 cm; slice number=188, slice thickness=1 mm. DTI images was acquired by single shot echo planar imaging sequence with a clinically oriented protocol. The DTI sequence parameters are TR/TE = 4600/86.6 ms, FOV =24cm ×24 cm, slice number = 33, slice thickness = 4 mm, matrix = 128 × 128,  FA = 90°, 25 diffusion gradient directions. A freehand oval region of interest (ROI) was placed in both white matter (bilateral frontal lobes, temporal lobes, occipital lobes, anterior cingulate cortex, posteriorcingulate cortex, centrum semiovale, corpus callosum genu and corpus callosum splenium) and grey matter (bilateral hippocampus, lenticular nucleus, head of caudate nucleus and thalamus. Numerical variables were denoted as the mean and standard deviation) (Fig1).

Characteristics of two groups were tested using independent samples t-test and Chi Square tests. The difference of DTI measures (FA and DCavg) of each ROIs between two groups were tested using independent samples t-test.

As shown in Fig 2, FA value of T2DM group was lower in the right frontal lobe, right temporal lobe, bilateral anterior cingulate cortex and centrum semiovale compared to healthy controls (P<0.05). Compared to the health controls, FA value of T2DM group was higher in bilateral lenticular nucleus and lower MD in left hippocampus (P<0.05).Besides，significant volumetric differences were observed in the default mode network (highlighted by black circles), left superior frontal gyrus (red circle) and right precuneus(p<0.05) (Fig3). This study demonstrated that there are brain microstructure changes of T2DM patients in both matter and grey matter. Corresponding, significant volumetric differences were observed in the default mode network. DTI combined with VBM technique can be used to quantitate the brain microstructure changes accurately in patients with T2DM.