Weaker Functional Connectivity Strength in Patients with Type 2 Diabetes Mellitus

Liu, Linlin; Li, Wanhu; Yang, Zhi‐gang; Qin, Wen; Lu, Shan; Zhang, Quan

doi:10.3389/fnins.2017.00390

Cited by 16 publications

(16 citation statements)

References 95 publications

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“…Through correlation analysis, we found that the abnormal functional connectivity of the T2D group was positively correlated with clinical variables of diabetes, such as FPG, 2hPG, HbA 1c , and HOMA-IR. A correlation between HbA1c levels and brain function connectivity has also been reported in previous studies (Xia et al, 2015; Liu et al, 2017). Studies have shown that poor glycemic control leading to long-term chronic exposure to hyperglycemia may be a decisive factor in T2D brain damage (Manschot et al, 2007).…”

Section: Discussionsupporting

confidence: 85%

Pathological Between-Network Positive Connectivity in Early Type 2 Diabetes Patients Without Cerebral Small Vessel Diseases

Liu

et al. 2019

Front. Neurosci.

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Background and Purpose Previous neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural and functional changes are partly associated with cognitive decline. However, less is known about the underlying mechanisms. Chronic hyperglycemia and microvascular complications are the two of most important risk factors related to cognitive decline in diabetes. Cerebral small vessel diseases (CSVDs), such as those defined by lacunar infarcts, white matter hyperintensities (WMHs) and microhemorrhages, are also associated with an increased risk of cognitive decline and dementia. In this study, we examined brain magnetic resonance imaging (MRI) changes in patients in the early stages of T2D without CSVDs to focus on glucose metabolism factors and to avoid the interference of vascular risk factors on T2D-related brain damage. Methods T2D patients with disease durations of less than 5 years and without any signs of CSVDs ( n = 34) were compared with healthy control subjects ( n = 24). Whole-brain region-based functional connectivity was analyzed with network-based statistics (NBS), and brain surface morphology was examined. In addition, the Montreal Cognitive Assessment (MoCA) was conducted for all subjects. Results At the whole-brain region-based functional connectivity level, thirty-three functional connectivities were changed in T2D patients relative to those in controls, mostly manifested as pathological between-network positive connectivity and located mainly between the sensory-motor network and auditory network. Some of the connectivities were positively correlated with blood glucose level, insulin resistance, and MoCA scores in the T2D group. The network-level analysis showed between-network hyperconnectivity in T2D patients, but no significant changes in within-network connectivity. In addition, there were no significant differences in MoCA scores or brain morphology measures, including cortical thickness, surface area, mean curvature, and gray/white matter volume, between the two groups. Conclusion The findings indicate that pathological between-network positive connectivity occurs in the early stages of T2D without CSVDs. The abnormal connectivity may indicate that the original balance of mutual antagonistic/cooperative relationships between the networks is broken, which may be a neuroimaging basis for predicting cognitive decline in early T2D patients.

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Section: Discussionsupporting

confidence: 85%

Pathological Between-Network Positive Connectivity in Early Type 2 Diabetes Patients Without Cerebral Small Vessel Diseases

Liu

et al. 2019

Front. Neurosci.

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“…The disruption in the balance between long- and short-range FCD may suggest a shift from the costly metabolic connection to an economic connection. Previous studies have reported alterations in long- and short-range functional connectivity strength ( Liu et al, 2017 ), and local and remote brain activity synchronization in T2DM patients ( Liu et al, 2016 ). The present study further suggests that T2DM patients have more short-range connections and fewer long-range connections.…”

Section: Discussionmentioning

confidence: 99%

“…As an approach for functional integration, the analysis of long- and short-range functional connections facilitates the investigation of brain dysfunction in patients with schizophrenia ( Guo et al, 2015 ), minimal hepatic encephalopathy ( Qi et al, 2015 ), non-alcoholic cirrhosis after liver transplantation ( Zhang et al, 2015a ), end-stage renal disease ( Zhang et al, 2015b ) and conduct disorder ( Lu et al, 2017 ). Previous studies have also suggested that T2DM patients may suffer from cognition decline linked to alterations in long- and short-range brain functional synchronization and functional connectivity strength ( Liu et al, 2016 , 2017 ). In addition to the aforementioned neuroimaging indicators, the functional connectivity density (FCD), which quantifies the number of functional connections between a given voxel and the remaining voxels in the entire brain, is a graph theoretical indicator to analyze the complex brain networks ( Tomasi et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Disrupted Balance of Long- and Short-Range Functional Connectivity Density in Type 2 Diabetes Mellitus: A Resting-State fMRI Study

Liu

Chen²,

Duan

et al. 2018

Front. Neurosci.

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Previous studies have shown that type 2 diabetes mellitus (T2DM) can accelerate the rate of cognitive decline in patients. As an organ with high energy consumption, the brain network balances between lower energy consumption and higher information transmission efficiency. However, T2DM may modify the proportion of short- and long-range connections to adapt to the inadequate energy supply and to respond to various cognitive tasks under the energy pressure caused by homeostasis alterations in brain glucose metabolism. On the basis of the above theories, this study determined the abnormal functional connections of the brain in 32 T2DM patients compared with 32 healthy control (HC) subjects using long- and short-range functional connectivity density (FCD) analyses with resting-state fMRI data. The cognitive function level in these patients was also evaluated by neuropsychological tests. Moreover, the characteristics of abnormal FCD and their relationships with cognitive impairment were investigated in T2DM patients. Compared with the HC group, T2DM patients exhibited decreased long-range FCD in the left calcarine and left lingual gyrus and increased short-range FCD in the right angular gyrus and medial part of the left superior frontal gyrus (p < 0.05, Gaussian random-field theory corrected). In T2DM patients, the FCD z scores of the medial part of the left superior frontal gyrus were negatively correlated with the time cost in part B of the Trail Making Test (ρ = -0.422, p = 0.018). In addition, the FCD z scores of the right angular gyrus were negatively correlated with the long-term delayed recall scores of the Auditory Verbal Learning Test (ρ = -0.356, p = 0.049) and the forward scores of the Digital Span Test (ρ = -0.373, p = 0.039). T2DM patients exhibited aberrant long-range and short-range FCD patterns, which may suggest brain network reorganization at the expense of losing the integration of long-range FCD to adapt to the deficiency in energy supply. These changes may be associated with cognitive decline in T2DM patients.

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“…The DC in RESTplus software was used to calculate the DC value based on correlation thresholds (absolute value of Pearson's r > 0.2) to exclude weak correlations, which may be caused by signal noise based on previous studies ( 22 , 33 , 34 ). Then smooth was performed with a 6 × 6 × 6 mm 3 Gaussian kernel.…”

Section: Methodsmentioning

confidence: 99%

“…Kolmogorov–Smirnov test ( 33 ) was applied to detect the normality of the continuous variables, including the demographic data and biochemical characteristics of the T2DM subjects and HCs. Independent two-sample t -tests were used if the data meet normal distribution and variance homogeneity; otherwise, Mann–Whitney non-parametric tests were used.…”

Section: Methodsmentioning

confidence: 99%

Altered Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Without Mild Cognitive Impairment

Liang

Tan

et al. 2020

Front. Neurol.

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Background: Type 2 diabetes mellitus (T2DM)-related cognitive decline is associated with neuroimaging changes. However, only a few studies have focused on early functional alteration in T2DM prior to mild cognitive impairment (MCI). This study aimed to investigate the early changes of global connectivity patterns in T2DM by using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Methods: Thirty-four T2DM subjects and 38 age-, sex-, and education-matched healthy controls (HCs) underwent rs-fMRI in a 3T MRI scanner. Degree centrality (DC) was used to identify the functional hubs of the whole brain in T2DM without MCI. Then the functional connectivity (FC) between hubs and the rest of the brain was assessed by using the hub-based approach. Results: Compared with HCs, T2DM subjects showed increased DC in the right cerebellum lobules III-V. Hub-based FC analysis found that the right cerebellum lobules III-V of T2DM subjects had increased FC with the right cerebellum crus II and lobule VI, the right temporal inferior/middle gyrus, and the right hippocampus. Conclusions: Increased DC in the right cerebellum regions III-V, as well as increased FC within cerebellar regions and ipsilateral cerebrocerebellar regions, may indicate an important pathophysiological mechanism for compensation in T2DM without MCI.

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Weaker Functional Connectivity Strength in Patients with Type 2 Diabetes Mellitus

Cited by 16 publications

References 95 publications

Pathological Between-Network Positive Connectivity in Early Type 2 Diabetes Patients Without Cerebral Small Vessel Diseases

Pathological Between-Network Positive Connectivity in Early Type 2 Diabetes Patients Without Cerebral Small Vessel Diseases

Disrupted Balance of Long- and Short-Range Functional Connectivity Density in Type 2 Diabetes Mellitus: A Resting-State fMRI Study

Altered Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Without Mild Cognitive Impairment

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