| BackgroundType 1 diabetes mellitus(T1 DM)is a type of diabetes characterized by the absolute deficiency of insulin caused by the dysplasia of the immune system or immune stress.It often occurs in children and adolescents.The incidence of T1DM in children has increased year by year.With the progress of T1DM,such patients may have complications such as retinopathy,cardiovascular and cerebrovascular accidents,ketoacidosis,which are important causes of disability and death in T1DM patients.The impact of T1DM on cognitive function has received increasing attention.Studies have shown that T1DM can cause neurocognitive impairments in children,mainly in the overall intelligence,memory,attention,executive ability,visual spatial ability,psychomotor speed,and literacy,of which characteristic impairment in intelligence and memory.Usually,the earlier the onset and the longer the disease duration,and the more severe the impairment of cognitive function.However,recent studies had found that cognitive function can be affected even at the beginning of T1DM.The mechanism of cognitive impairment associated with T1DM is complex and is the result of multiple factors and multiple aspects.Although there is some understanding of T1DM,the research is not deep enough.Previous studies have shown that neurological and structural changes in the brain often precede cognitive dysfunction related clinical symptoms.Therefore,the evaluation of brain function and structure from various aspects not only contributes to the understanding of the pathogenesis of TIDM-related cognitive dysfunction,but also may help to achieve early diagnosis and interventional treatment of TIDM-related cognitive dysfunction.Currently,MRI has been used to study cognitive dysfunction in children with T1DM,and the brain structure and function can be systematically and comprehensively evaluated by several image parameters.Three-dimensional T1-weighted imaging can be used to reflect neuronal degeneration(gray atrophy)in the brain.It is found that T1DM can cause a wide range of changes in brain gray matter structure and cognitive function in children,and there is a correlation between them.Changes in the structure of the gray matter can be an early biomarker of neuronal damage or degeneration.In addition,resting state functional magnetic resonance imaging is used for brain function studies in patients with T1DM.Previous studies focused on adult patients,and there is currently only one study focused on resting state functional magnetic resonance imaging in children.This study found that there are functional connectivity changes in some brain regions of T1DM children,and these changes are associated with cognitive function,suggesting that children with T1DM have functional connectivity abnormalities associated with pathophysiology of cognitive impairment.The subjects had a disease duration of more than 2 years,and the brain structure and functional changes in the new-onset T1DM children are still unclear.Therefore,the present study attempted to analyze changes in brain gray matter volume,neural activity,and brain functional connectivity by analyzing 3D-T1WI structural data and resting-state functional magnetic resonance imaging data,and combine clinical and cognitive data.The results will reveal the impact of TIDM on brain strueture,function and cognition in children,will help understand the brain structure and functional basis of cognitive impairment in TIDM children,and will provide a new functional magnetic resonance imaging basis for scientific intervention and treatment of TIDM in children.Part Ⅰ Voxel-based morphometry study of gray matter in children with new-onset type 1 diabetes mellitusPurposesThis study compared the gray matter volume(GMV)between children with new-onset type 1 diabetes(T1DM)and normal controls and analyzed the correlation between GMV and clinical and cognitive data to investigate the changes in gray matter structure and clinical parameters and the relationship between them in children with new-onset T1DM.Materials and MethodsThis study included 35 children with new-onset T1DM and 35 age and sex matched normal controls.Demographic sociological data,clinical data and intelligence assessment data were collected.High-resolution three-dimensional structural images of all subjects were acquired by using the 3D T1-BRAVO sequence,and an axial T2WI sequence was routinely added to rule out intracranial disease.The 3D-T1WI structure image data was format converted and then was analyzed by voxel-based morphology analysis on FSL4.1 software.Differences in demographic and clinical data were analyzed using an independent sample t test or the Mann-Whitney U test.A partial correlation analysis was performed between the extracted GMV and clinical variables,age and gender as covariates.P<0.05 was considered to be statistically significant.ResultsThere was no significant difference in age and gender between the diabetic group and the control group(P>0.05).The HbAlc and blood glucose levels before imaging in the diabetic group were significantly higher than those in the control group(P<0.05).There was no significant change in the total IQ of the diabetic group when compared with the control group(P>0.05).Compared with the control group,the GMV of the right middle and inferior temporal gyri,right lingual gyrus,and left superior frontal gyrus was significantly decreased in the diabetic group.In addition,compared with the control group,the diabetic group did not have an increase in GMV in any brain region.In T1DM subjects,the GMV of the right middle temporal gyrus was positively correlated with IQ but was negatively correlated with HbAle.ConclusionsThese brain structural changes indicate that gray matter abnormalities occur at the beginning of T1DM,and that brain tissue integrity is affected by T1DM and its metabolic disorders,and this structural change is earlier than IQ change.These gray matter changes may be one of the possible mechanisms of cognitive impairment(such as language,visual and memory impairment)in T1DM children.Recent glucose variability may affect regional GMV in children with T1DM.Part Ⅱ Resting state functional magnetic resonance imaging study of spontaneous brain activity based on fALFF in children with new-onset type 1 diabetes mellitusPurposesThis study compared the spontaneous fractional amplitude of low-frequency fluctuation(fALFF)between children with new-onset type 1 diabetes mellitus(T1DM)and normal controls and analyzed the correlation between fALFF and clinical and cognitive data to explore the changes of spontaneous brain activity and relationships between these changes and clinical parameters and cognition in children with new-onset T1 DM.Materials and MethodsThis study included 35 children with new-onset T1DM and 33 age and sex matched normal controls.Demographic sociological data,clinical data and intelligence assessment data were collected.Resting state functional magnetic resonance images of all subjects were acquired using whole brain plane echo imaging sequences,and high-resolution three-dimensional structural images were acquired by using the 3D T1-BRAVO sequence.Resting state functional magnetic resonance imaging data was processed using SPM8 and DPARSF software,and fALFF was calculated using REST software.A two-sample t test was used to detect the difference in fALFF between the two groups and multiple comparison corrections were performed.When the cluster size was>40 voxels,the statistical threshold was set to P<0.01,corresponding to a corrected P<0.05.Spearman rho correlation was used to analyze the correlation between abnormal brain region fALFF and clinical variables and IQ Z scores.P<0.05 was considered to be statistically significant.ResultsThere was no significant difference in age,gender,and IQ between the diabetic group and the control group(P>0.05).The HbAlc and blood glucose levels before imaging in the diabetic group were higher than those in the control group(P<0.05).Compared with the control group,the fALFF value of the left middle temporal gyrus and right calcarine of the diabetic group was significantly increased,and the fALFF value of the right thalamus was significantly decreased.In the diabetic group,the fALFF value in the left middle temporal gyrus was positively correlated with total IQ,and the fALFF value in the right thalamus was negatively correlated with blood glucose level before imaging.ConclusionsThe results of this study indicate that brain spontaneous neural activity in the left middle temporal gyrus,calcarine,and right thalamus is affected at rest in children with new-onset T1DM.In these children,spontaneous neural activity in the left middle temporal gyrus may affect IQ,while blood glucose level before imaging may affect spontaneous neural activity in the right thalamus.Changes in spontaneous neural activity in these brain regions may be important neuropathophysiological features in early stage of T1DM and may be the mechanism of future visual impairment,cognitive dysfunction,and depression in patients with T1DM.Part Ⅲ Resting state functional magnetic resonance imaging study of functional connectivity in children with new-onset type 1 diabetes mellitusPurposesThis study compared the difference in whole brain functional connectivity between children with new-onset type 1 diabetes mellitus(T1DM)and normal controls,and analyzed the correlation between functional connectivity density and clinical and cognitive data.Using brain regions with difference in functional connectivity density as seed points,functional connectivity with whole brain voxels was calculated,and functional connection changes between the two groups were analyzed.Materials and MethodsThis study included 35 children with new-onset T1DM and 33 age and sex matched normal controls.Demographic sociological data,clinical data and intelligence assessment data were collected.Resting state functional magnetic resonance images of all subjects were acquired using whole brain plane echo imaging sequences,and high-resolution three-dimensional structural images were acquired by using the 3D T1-BRAVO sequence.Resting state functional magnetic resonance imaging data was processed using SPM8 and DPARSF software,then the functional connectivity density of the whole brain of each subject was calculated.Brain regions with difference in functional connectivity density were selected as the seed point,then the whole brain functional connection was calculated for each subject.Comparison of functional connectivity density or voxels on functional connectivity maps between the two groups was performed using a two-sample t-test,then multiple comparison corrections were performed to correct the results.The statistical difference was set to uncorrected P<0.005(voxel number>30),corresponding to the corrected P<0.05.All demographic and clinical data were tested using a two-sample t-test.In the diabetic group,partial correlation was performed between functional connectivity density and clinical data,age and gender as covariates.P<0.05 was considered statistically significant.ResultsThere was no significant difference in age,gender,and IQ between the diabetic group and the control group(P>0.05).The HbAlc and blood glucose level before imaging in the diabetic group were higher than those in the control group(P<0.05).Compared with the control group,the functional connectivity density of the right inferior temporal gyrus and the right posterior cingulate gyrus of the diabetic group was decreased.In the diabetic group,the functional connectivity density of the right inferior temporal gyrus and the right posterior cingulate gyrus was not correlated with HbAle,blood glucose level before imaging,and total IQ.In the diabetic group,the functional connectivity between the right inferior temporal gyrus and the left orbital part of inferior frontal gyrus was increased,and the functional connectivity between the right posterior cingulate gyrus and the right cuneus was reduced.ConclusionsThis study found that even in the initial stage of the disease,the functional connectivity of some brain regions has changed in children with T1DM.Abnormal functional connectivity in right inferior temporal gyrus,posterior cingulate gyrus,and cuneus may be one of the underlying causes of behavioral(emotional)and cognitive(memory,attention,executive function)changes in T1DM children. |
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