Effects of Acetylcholine on Endothelial Function and Nitric Oxide Levels in Patients with Type 2 Diabetes Mellitus: A...

Peripheral neuropathy is a prevalent neurological disorder with multiple etiologies. Nerve damage frequently occurs due to prolonged high blood sugar levels and diabetes. Peripheral nerve fiber impairment, mediated mainly through dysregulation of Nitric Oxide Synthase (NOS) activity, induces irreversible structural damage. Acetylcholine induces vasodilation by stimulating endothelial nitric oxide (NO) production, which relaxes smooth muscle, and by triggering a nerve axon reflex. This reflex releases neuropeptides like substance P, which further dilate vessels and prompt histamine release. This study aims to evaluate the effects of Acetylcholine (Ach) iontophoresis as a vasodilator on endothelial NOS activity to develop a non-invasive transdermal treatment that is effective and devoid of systemic adverse side effects.

Eighty patients, both male and female, diagnosed with type 2 Diabetes Mellitus were randomly assigned to two groups. The experimental group (A) underwent iontophoresis using acetylcholine for 15 min three times a week for four weeks. The control group (B) underwent 15-minute sessions of sham iontophoresis three times a week for four weeks. Nitric oxide levels and nerve conduction studies of peripheral nerves were assessed pre and post-treatment for both groups.

The study demonstrated a statistically significant improvement in endothelium-dependent vasodilation and Nitric Oxide (NO) levels in Group A compared to Group B. However, no significant differences were observed between the groups in terms of electrophysiological outcomes for peripheral nerves and muscles, both pre- and post-treatment.

Repeated acetylcholine iontophoresis significantly improved microvascular function, increasing nitric oxide release and tissue perfusion in patients with diabetic neuropathy. While no immediate changes in peripheral nerve conduction were observed, the intervention shows promise as an adjunctive strategy for supporting microvascular health in diabetic neuropathic complications.