Dysfunction of the brain-gut axis in diabetic gastroparesis: Underlying mechanisms and therapeutic strategies

Table 2 Comparison of neuromodulatory approaches targeting the brain-gut axis in diabetic gastroparesis

Neuromodulation modality	Target population/stage	Main therapeutic effects	Proposed mechanisms
GES	Refractory DGP, particularly patients with severe nausea and vomiting	Marked reduction in vomiting frequency and overall symptom improvement; variable effects on gastric emptying	Activation of vagal afferent pathways, modulation of gastric electrical rhythms, promotion of ENS synaptic regeneration, and improvement of ICC function
GES combined with pyloroplasty	DGP with prominent pyloric dysfunction	Greater improvement in symptoms and gastric emptying compared with single intervention	Synergistic effects of neuromodulation and mechanical outflow relief, enhancing remodeling of peripheral effector components of the brain-gut axis
VNS/transcutaneous VNS	DGP with autonomic dysfunction or central regulatory abnormalities	Symptom improvement and partial acceleration of gastric emptying, with inconsistent results across randomized controlled trials	Enhancement of vagal efferent activity, modulation of central-peripheral brain-gut signaling, and activation of cholinergic anti-inflammatory reflexes
Intrapyloric botulinum toxin injection	DGP associated with pyloric spasm	Short-term improvement in gastric emptying and symptoms; limited long-term efficacy	Local inhibition of acetylcholine release and smooth muscle excitability, with limited capacity for sustained brain-gut axis remodeling
Low-energy shockwave	Experimental stage (preclinical DGP models)	Improvement of gastric contractile function and increased density of enteric neuromuscular plexuses	Promotion of axonal regeneration and enhancement of gastrointestinal neuromuscular structural integrity
EA/transcutaneous EA	Mild to moderate DGP or adjunctive therapy	Improvement of nausea, restoration of gastric slow-wave rhythm, and acceleration of gastric emptying	Regulation of autonomic balance via the nucleus tractus solitarius-vagal pathway, restoration of excitatory-inhibitory neurotransmitter balance in the ENS, and promotion of ICC protection and regeneration
Low-intensity pulsed ultrasound	Experimental stage (preclinical DGP models)	Acceleration of gastric emptying and improvement of ICC network integrity	Inhibition of the tumor necrosis factor-α/Ikappa B kinase beta/nuclear factor-kappa B inflammatory pathway and restoration of ENS-ICC coupling

DGP: Diabetic gastroparesis; EA: Electroacupuncture; ENS: Enteric nervous system; GES: Gastric electrical stimulation; ICC: Interstitial cells of Cajal; VNS: Vagus nerve stimulation.