Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study

Diabetologia. 1989 Jul;32(7):427-33. doi: 10.1007/BF00271262.


Immunocytochemistry for the general neuronal marker protein gene product 9.5 and four neuropeptides (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide and neuropeptide Y) was performed on 20 skin biopsy specimens from 19 diabetic patients, age range 20-75 years, 17 Type 2 (non-insulin-dependent) and 3 Type 1 (insulin-dependent). Fifteen specimens were from the lower limb, 3 from the upper limb and 2 from the abdominal wall. Seven subjects had lower limb neurophysiological tests. All but one specimen showed reduced protein gene product 9.5 and neuropeptide immunoreactivity. Reduced protein gene product 9.5 and neuropeptide immunoreactivity was found in specimens taken from the abdominal wall and hand as well as those from the leg, and also in specimens from patients undergoing amputation for peripheral vascular disease. In general, the greater the number of abnormal neurophysiological tests, the greater the extent of neuronal abnormalities. Three patients with normal tests had abnormalities of dermal innervation. While these changes are also found in other axonal neuropathies, in the absence of other causes of peripheral nerve disease and of macrovascular disease, immunocytochemistry of skin biopsies may have a role in the assessment of diabetic neuropathy and its response to treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Calcitonin Gene-Related Peptide / analysis
  • Diabetes Mellitus / pathology*
  • Diabetic Neuropathies / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neuropeptide Y / analysis
  • Neuropeptides
  • Skin / metabolism
  • Substance P / analysis
  • Ubiquitin Thiolesterase
  • Vasoactive Intestinal Peptide / analysis


  • Neuropeptide Y
  • Neuropeptides
  • Substance P
  • Vasoactive Intestinal Peptide
  • Ubiquitin Thiolesterase
  • Calcitonin Gene-Related Peptide