Abstract
Alterations of brain functional connectivity in patients with type 2 diabetes mellitus (T2DM) have been reported by resting-state functional magnetic resonance imaging studies, but the underlying precise neuropathological mechanism remains unclear. This study is aimed at investigating the implicit alterations of functional connections in T2DM by integrating functional connectivity strength (FCS) and Granger causality analysis (GCA) and further exploring their associations with clinical characteristics. Sixty T2DM patients and thirty-three sex-, age-, and education-matched healthy controls (HC) were recruited. Global FCS analysis of resting-state functional magnetic resonance imaging was performed to explore seed regions with significant differences between the two groups; then, GCA was applied to detect directional effective connectivity (EC) between the seeds and other brain regions. Correlations of EC with clinical variables were further explored in T2DM patients. Compared with HC, T2DM patients showed lower FCS in the bilateral fusiform gyrus, right superior frontal gyrus (SFG), and right postcentral gyrus, but higher FCS in the right supplementary motor area (SMA). Moreover, altered directional EC was found between the left fusiform gyrus and bilateral lingual gyrus and right medial frontal gyrus (MFG), as well as between the right SFG and bilateral frontal regions. In addition, triglyceride, insulin, and plasma glucose levels were correlated with the abnormal EC of the left fusiform, while disease duration and cognitive function were associated with the abnormal EC of the right SFG in T2DM patients. These results suggest that T2DM patients show aberrant brain function connectivity strength and effective connectivity which is associated with the diabetes-related metabolic characteristics, disease duration, and cognitive function, providing further insights into the complex neural basis of diabetes.
Highlights
Type 2 diabetes mellitus (T2DM) is proving to be a major global health burden, affecting over 400 million people worldwide [1]
T2DM patients and healthy controls (HC) were matched for age, gender, and education
T2DM patients performed relatively worse on Montreal Cognitive Assessment (MoCA), but no significant difference was observed between T2DM and HC (Table 1)
Summary
Type 2 diabetes mellitus (T2DM) is proving to be a major global health burden, affecting over 400 million people worldwide [1]. Insulin resistance and chronic hyperglycemia in synergy with other metabolic aberrations in T2DM can adversely affect various organ systems including the brain, causing a range of microvascular and macrovascular complications which can lead to the cognitive dysfunction and the increased risk of dementia [2]. Once clinical symptoms of dementia appear, the progression cannot be reversed by current treatments. Early detection of high-risk factors and biomarkers of brain dysfunction in T2DM patients is crucial for timely prevention and treatment [3, 4]. Subtle abnormities of the brain structure and function have already occurred in the T2DM patients before the clinically measurable cognitive dysfunction [5, 6], but the underlying neural mechanisms have not been fully elucidated.
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