Network-level structural abnormalities of cerebral cortex in type 1 diabetes mellitus.
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ABSTRACT:
SUBMITTER: Lyoo IK
PROVIDER: S-EPMC3751935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The role of the cerebellum in type 2 diabetes mellitus (T2DM) has been receiving increased attention. However, the functional connectivity (FC) between the cerebellar subregions and the cerebral cortex has not been investigated in T2DM. Therefore, the purpose of this study was to investigate cerebellar-cerebral FC and the relationship between FC and clinical/cognitive variables in patients with T2DM. A total of 34 patients with T2DM and 30 healthy controls were recruited for this study to receive a neuropsychological assessment and undergo resting-state FC. We selected four subregions of the cerebellum (bilateral lobules IX, right and left Crus I/II, and left lobule VI) as regions of interest (ROIs) to examine the differences in cerebellar-cerebral circuits in patients with T2DM compared to healthy controls. Correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables in the patients. Compared to healthy controls, patients with T2DM showed significantly decreased cerebellar-cerebral FC in the default-mode network (DMN), executive control network (ECN), and visuospatial network (VSN). In the T2DM group, the FC between the left cerebellar lobule VI and the right precuneus was negatively correlated with the Trail Making Test A (TMT-A) score (r = -0.430, P = 0.013), after a Bonferroni correction. In conclusion, patients with T2DM have altered FC between the cerebellar subregions and the cerebral networks involved in cognitive and emotional processing. This suggests that a range of cerebellar-cerebral circuits may be involved in the neuropathology of T2DM cognitive dysfunction.
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Project description:We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.
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Project description:Background and purposeIncreasing DTI studies have demonstrated that white matter microstructural abnormalities play an important role in type 2 diabetes mellitus-related cognitive impairment. In this study, the diffusional kurtosis imaging method was used to investigate WM microstructural alterations in patients with type 2 diabetes mellitus and to detect associations between diffusional kurtosis imaging metrics and clinical/cognitive measurements.Materials and methodsDiffusional kurtosis imaging and cognitive assessments were performed on 58 patients with type 2 diabetes mellitus and 58 controls. Voxel-based intergroup comparisons of diffusional kurtosis imaging metrics were conducted, and ROI-based intergroup comparisons were further performed. Correlations between the diffusional kurtosis imaging metrics and cognitive/clinical measurements were assessed after controlling for age, sex, and education in both patients and controls.ResultsAltered diffusion metrics were observed in the corpus callosum, the bilateral frontal WM, the right superior temporal WM, the left external capsule, and the pons in patients with type 2 diabetes mellitus compared with controls. The splenium of the corpus callosum and the pons had abnormal kurtosis metrics in patients with type 2 diabetes mellitus. Additionally, altered diffusion metrics in the right prefrontal WM were significantly correlated with disease duration and attention task performance in patients with type 2 diabetes mellitus.ConclusionsWith both conventional diffusion and additional kurtosis metrics, diffusional kurtosis imaging can provide additional information on WM microstructural abnormalities in patients with type 2 diabetes mellitus. Our results indicate that WM microstructural abnormalities occur before cognitive decline and may be used as neuroimaging markers for predicting the early cognitive impairment in patients with type 2 diabetes mellitus.
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Project description:Pancreatic islet microcirculation, consisting of pancreatic islet microvascular endothelial cells (IMECs) and pericytes (IMPCs), provides crucial support for the physiological function of pancreatic islet. Emerging evidence suggests that pancreatic islet microcirculation is impaired in type 1 diabetes mellitus (T1DM). Here, we investigated the potential ultrastructural protective effects of insulin against streptozotocin (STZ)-induced ultrastructural abnormalities of the pancreatic islet microcirculation in T1DM mouse model. For this purpose, pancreatic tissues were collected from control, STZ-induced T1DM and insulin-treated mice, and a pancreatic IMECs cell line (MS1) was cultured under control, 35 mM glucose with or without 10-8 M insulin conditions. Transmission and scanning electron microscopies were employed to evaluate the ultrastructure of the pancreatic islet microcirculation. We observed ultrastructural damage to IMECs and IMPCs in the type 1 diabetic group, as demonstrated by destruction of the cytoplasmic membrane and organelles (mainly mitochondria), and this damage was substantially reversed by insulin treatment. Furthermore, insulin inhibited collagenous fiber proliferation and alleviated edema of the widened pancreatic islet exocrine interface in T1DM mice. We conclude that insulin protects against T1DM-induced ultrastructural abnormalities of the pancreatic islet microcirculation.
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Project description:Diabetes Mellitus Type 1 miRnome
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Project description:Cortical asymmetry is a ubiquitous feature of brain organization that is subtly altered in some neurodevelopmental disorders, yet we lack knowledge of how its development proceeds across life in health. Achieving consensus on the precise cortical asymmetries in humans is necessary to uncover the developmental timing of asymmetry and the extent to which it arises through genetic and later influences in childhood. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in seven datasets and chart asymmetry trajectories longitudinally across life (4-89 years; observations = 3937; 70% longitudinal). We find replicable asymmetry interrelationships, heritability maps, and test asymmetry associations in large-scale data. Cortical asymmetry was robust across datasets. Whereas areal asymmetry is predominantly stable across life, thickness asymmetry grows in childhood and peaks in early adulthood. Areal asymmetry is low-moderately heritable (max h2SNP ~19%) and correlates phenotypically and genetically in specific regions, indicating coordinated development of asymmetries partly through genes. In contrast, thickness asymmetry is globally interrelated across the cortex in a pattern suggesting highly left-lateralized individuals tend towards left-lateralization also in population-level right-asymmetric regions (and vice versa), and exhibits low or absent heritability. We find less areal asymmetry in the most consistently lateralized region in humans associates with subtly lower cognitive ability, and confirm small handedness and sex effects. Results suggest areal asymmetry is developmentally stable and arises early in life through genetic but mainly subject-specific stochastic effects, whereas childhood developmental growth shapes thickness asymmetry and may lead to directional variability of global thickness lateralization in the population.
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Project description:BackgroundObservational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown.MethodsIndependent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed.ResultsConsistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively).ConclusionOur MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.
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