Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes

Context: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. Objective: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. Design: Case-control study. Setting: Tertiary referral hospital. Participants: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. Intervention: None. Main Outcome Measures: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. Results: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. Conclusions: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.