Amelioration of diabetic autonomic neuropathy symptoms following a course of transcranial direct current stimulation

Abstract Cardiovascular autonomic neuropathy (CAN) is a severe and potentially life-threatening complication of diabetes. This randomized, sham-controlled, three-arm trial evaluated the efficacy of anodal transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex for improving CAN symptoms and glycemic control in older patients with insulin-dependent diabetes. Seventy-two participants (aged 60–80 years) with symptomatic CAN were randomly allocated to active tDCS (n = 24), sham tDCS (n = 24), or routine care only (control group, n = 24). The primary outcome was CAN severity quantified by the ratio of the change in systolic blood pressure to the change in heart rate measured three minutes after standing from a supine position; the secondary outcome was long-term glycemic control assessed by glycated hemoglobin. The active and sham groups received 30 sessions of tDCS (2 milliamperes for 20 minutes per session, anode at F3, cathode at Fp2) over 6–8 weeks. Outcomes were assessed at baseline, post-intervention, and one-month follow-up. Data were analyzed with mixed-design ANOVA. A significant Time × Group interaction was found for CAN severity (p < 0.001, partial eta squared = 0.165). The active tDCS group demonstrated significantly greater improvement in CAN symptoms from baseline to post-intervention compared with both the sham tDCS and control groups (p < 0.001), with these improvements remaining evident at one-month follow-up despite a small, non-significant numerical increase from post-intervention. The active tDCS group also achieved superior glycemic control at follow-up (mean glycated hemoglobin 7.92 ± 0.79%) relative to the sham group (8.78 ± 1.05%, p = 0.008) and control group (9.12 ± 1.18%, p = 0.001). Thirty sessions of left dorsolateral prefrontal cortex anodal tDCS was safe and well-tolerated. These findings indicate that left dorsolateral prefrontal cortex tDCS can improve cardiovascular autonomic function and glycemic control in older adults with diabetic CAN and warrant larger, longer-term, multi-center randomized controlled trials to confirm efficacy, durability, and generalizability.