Intraepidermal nerve-fibre density as a biomarker of the course of neuropathy in patients with Type2 diabetes mellitus

AimsThis paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type2 diabetes mellitus. MethodsSkin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type2 diabetes mellitus (median age 60years, 17 men) with a short duration of diabetes (<3years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were >2years (median 33.8months). Eighteen patients with Type2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. ResultsAt first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P<0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control. ConclusionsThe annual rate of IENF loss in patients with Type2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy. What's new? Intraepidermal nerve-fibre loss in patients with Type2 diabetes mellitus is not linear and should be expressed as a proportion of initial intraepidermal nerve-fibre density. Annual intraepidermal nerve-fibre loss as a marker of the progression of small-fibre neuropathy in patients with Type2 diabetes mellitus is several times higher compared with age-related intraepidermal nerve-fibre loss in age- and sex-matched people without diabetes. Change in intraepidermal nerve-fibre density in patients with Type2 diabetes mellitus of short duration and good glucose control is not dependent on the presence of neuropathy and degree of glucose control.