Dong Zhang1, Lin Shi2,3, Xiubao Song4, Changzheng Shi1, Pan Sun5, Wutao Lou5, Defeng Wang2,6,7,8, Liangping Luo1. 1. Department of Medical Imaging Centre, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China. 2. Research Centre for Medical Image Computing, Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, China. 3. Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China. 4. Department of Rehabilitation, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China. 5. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. 6. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100091, China. 7. School of Instrumentation Science and Opto-electronics Engineering, Beihang University, Beijing 100091, China. 8. Shenzhen SmartView MedTech Limited, Shenzhen 518000, China.
Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by notable familial aggregation involving common variants of many genes, and its heritability leads to a high prevalence in the siblings of affected individuals compared with the general population. Endophenotypes are objective, heritable, quantitative traits that appear to reflect the genetic risk for polygenic disorders at more biologically tractable levels. Based on a sibling pair design, we aimed to find the neuroimaging endophenotypes of T2DM and investigate the role of inherent neurological disorders in the pathogenesis and deterioration of T2DM. METHODS: Twenty-six pairs of diagnosed T2DM patients with unaffected siblings and 26 unrelated controls were included in this study. Both high-resolution structural MRI and three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) MRI data were acquired with a 3.0 T MRI system. Voxel-based morphometry (VBM) analysis was performed on the structural T1W images, and cerebral blood flow (CBF) maps were obtained. All data were processed with the SPM8 package under the MATLAB 7.6 operation environment. RESULTS: The T2DM patients and their unaffected siblings shared significant atrophy in the right inferior/middle temporal gyrus, and left insula, in addition to elevated CBF in the right prefrontal lobe. Several regions with abnormal CBF in siblings, including the right inferior/middle temporal gyrus, left insula, left operculum, right supramarginal gyrus, right prefrontal lobe, and bilateral anterior cingulate cortex, also presented significant atrophy in T2DM patients. CONCLUSIONS: The shared brain regions with grey matter (GM) loss and CBF increases may serve as neuroimaging endophenotypes of T2DM, and the regions with abnormal CBF in siblings indicate an increased risk for T2DM.
BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by notable familial aggregation involving common variants of many genes, and its heritability leads to a high prevalence in the siblings of affected individuals compared with the general population. Endophenotypes are objective, heritable, quantitative traits that appear to reflect the genetic risk for polygenic disorders at more biologically tractable levels. Based on a sibling pair design, we aimed to find the neuroimaging endophenotypes of T2DM and investigate the role of inherent neurological disorders in the pathogenesis and deterioration of T2DM. METHODS: Twenty-six pairs of diagnosed T2DM patients with unaffected siblings and 26 unrelated controls were included in this study. Both high-resolution structural MRI and three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) MRI data were acquired with a 3.0 T MRI system. Voxel-based morphometry (VBM) analysis was performed on the structural T1W images, and cerebral blood flow (CBF) maps were obtained. All data were processed with the SPM8 package under the MATLAB 7.6 operation environment. RESULTS: The T2DM patients and their unaffected siblings shared significant atrophy in the right inferior/middle temporal gyrus, and left insula, in addition to elevated CBF in the right prefrontal lobe. Several regions with abnormal CBF in siblings, including the right inferior/middle temporal gyrus, left insula, left operculum, right supramarginal gyrus, right prefrontal lobe, and bilateral anterior cingulate cortex, also presented significant atrophy in T2DM patients. CONCLUSIONS: The shared brain regions with grey matter (GM) loss and CBF increases may serve as neuroimaging endophenotypes of T2DM, and the regions with abnormal CBF in siblings indicate an increased risk for T2DM.
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