A Resting-state FMRI Study On Functional Connectivity Strength In Patients With Type 2 Diabetes Mellitus

Objective:Type 2 diabetes mellitus(T2DM)is related to cognitive impairments and is a risk factor for dementia.In this study,a data-driven whole-brain resting-state functional connectivity strength(FCS)method was used to detect the associations between the resting-state FCS changes and cognitive functions in cognitively intact T2 DM patients.Materials and Methods:Fifty-nine right-handed T2 DM patients(28 males and 31 females)and 59 gender,age and level of education-matched euglycemia healthy controls(HCs)(30 males and 29 females)were recruited in our study.None of patients had any T2DM-related complications including diabetic retinopathy,diabetic nephropathy or peripheral neuropathy.None of the patients has a history of hypoglycemia during the last two years.Demographic data,clinical data and cognitive assessment were collected in all subjects.MRI data were acquired using a 3.0-Tesla MR scanner(Discovery MR750,GE Milwaukee,WI,USA).Resting-state fMRI data were preprocessed using Statistical Parametric Mapping(SPM)software and DPARSF software.The data preprocessing were including slice timing,head motion correction,regressing out nuisance covariates,temporal filtering(0.01 to 0.08 Hz),and normalization.Whole-brain FC analysis were performed for the preprocessed data,and the resting-state FCS for a given voxel was calculated as the sum of the connectivities between this voxel and all other voxels.Based on the anatomical distance,the resting-state FCS was divided into long-and short-range resting-state FCS.Two-sample t-test embedded in SPM was performed to exam the intergroup differences in the long-and short-range resting-state FCS after controlling for gender age and years of education.Further,a seed-based method was conducted to analyze the FC of brain regions with a significant intergroup difference in long-or short-range resting-state FCS.Three-dimension T1 WI data were preprocessed using VBM8 tool-box of the SPM8 to perform intergroup comparisons in GMV.AlphaSim correction was used to control the multiple comparisons.SPSS 21.0(SPSS,Inc,Chiago.IL)was used to conduct intergroup comparisons in demographic and clinical variables between the two groups.Correlation analyses were conducted between resting-state FCS/FC changes and clinical/cognitive variables in the T2 DM and healthy controls groups.Results:There were no significant intergroup differences in demographics or cognitive performance in the T2 DM patients and HCs(P < 0.05).Compared with the controls,the patients had increased fasting blood glucose(P < 0.001)and Hb A1c(P < 0.001)levels.Compared with the HCs,the T2 DM patients exhibited reduced long-range resting-state FCS in the right insula,and decreased short-range resting-state FCS in the right supramarginal gyrus after controlling for the age,gender and years of education(P < 0.05,Alpha Sim correction).The FC between the right insula and the left postcentral/precentral gyrus,the left superior parietal lobule and right postcentral gyrus/ superior parietal lobule decreased in T2 DM patients compared with the HCs.Additionally,the T2 DM patients have declined FC between the right superior parietal lobule and the bilateral supplementary motor area,the right postcentral gyrus and the right superior parietal lobule(P < 0.05,Alpha Sim correction).Voxel-wise comparisons revealed no significant difference in GMV within the whole brain between the two groups(P < 0.05,Alpha Sim correction).Significant negative correlation was found between the long-range resting-state FCS of the right insula and HbA1 c levels in T2 DM patients(r =-0.361,P = 0.046).The FC between the right superior parietal lobule and the bilateral supplementary motor area negatively correlated with TMT-A in T2 DM patients(r =-0.436,P = 0.014).Conclusion:The T2DM patients exhibited decreased long-range resting-state FCS in the right insula and decreased short-range resting-state FCS in the right superior parietal lobule.Our results indicated that the resting-state FCS alteration occurred before cognitive deficits in T2 DM patients and might provide a neuroimaging biomarker for predicting early cognitive declines in T2 DM patients.