The effects of vasoactive intestinal polypeptide and substance P on methacholine-induced sweating and vascular flare in diabetic neuropathy

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.