A Single-Blinded Trial Using Resting-State Functional Magnetic Resonance Imaging of Brain Activity in Patients with Type 2 Diabetes and Painful Neuropathy

ABSTRACT: About two-thirds of patients with painful diabetic neuropathy (PDN) suffer from anxiety and/or depression disorders. However, the pathogenesis of PDN is unclear, in particular with respect to the mechanism associated with the central nervous system. We used the neuroimaging techniques of fraction amplitude of low-frequency fluctuation (fALFF) and regional homogeneity of resting-state functional magnetic resonance imaging (fMRI) to explore the brain activity in patients with PDN. The symptoms, signs and mental conditions of 19 patients with PDN and of 18 patients with non-pain neuropathy were assessed separately and compared. Blood oxygenation level-dependent resting-state fMRI scans of the brain were performed in all 37 patients with neuropathy and in 15 gender- and age-matched healthy controls. Our data showed that patients with PDN had increased insulin resistance (p = 0.03), increased depression (p = 0.02) and increased anxiety (p < 0.001) compared with the controls and that all of these conditions were associated with abnormal spontaneous activities in several regions of the brain, including the somatosensory, cognitive and emotional regions. The duration of diabetes, level of glycated hemoglobin, homeostasis model assessment of insulin resistance and estimated glomerular filtration rate were significantly correlated to abnormal spontaneous activity in patients’ brains. These results lead to the conclusion that patients with PDN have abnormal brain activity, indicating that the central nervous system may contribute to painful diabetic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03700502.