Intraepidermal nerve-fibre density as a biomarker of the course of neuropathy in patients with Type 2 diabetes mellitus.
OBJECTIVE
This paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus.


METHODS
Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy.


RESULTS
At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/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.


CONCLUSIONS
The annual rate of IENF loss in patients with Type 2 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.
Central European Institute of Technology, Applied Neuroscience, Masaryk University Brno, Czech Republic.|Department of Neurology, University Hospital Brno, Czech Republic.
S
S
Divisova
Central European Institute of Technology, Applied Neuroscience, Masaryk University Brno, Czech Republic.|Department of Neurology, University Hospital Brno, Czech Republic.
E
E
Vlckova
Central European Institute of Technology, Applied Neuroscience, Masaryk University Brno, Czech Republic.|Department of Neurology, University Hospital Brno, Czech Republic.
I
I
Srotova
Central European Institute of Technology, Applied Neuroscience, Masaryk University Brno, Czech Republic.|Department of Neurology, University Hospital Brno, Czech Republic.
S
S
Kincova
Department of Neurology, University Hospital Brno, Czech Republic.
M
M
Skorna
Insitute of Biostatistics and Analyses, Masaryk University Brno, Czech Republic.
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L
Dusek
Central European Institute of Technology, Cellular and Molecular Neurobiology, Masaryk University Brno, Czech Republic.
P
P
Dubovy
Central European Institute of Technology, Applied Neuroscience, Masaryk University Brno, Czech Republic.|Department of Neurology, University Hospital Brno, Czech Republic.
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J
Bednarik
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001706:Biopsy; D002452:Cell Count; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000628:therapy; D003929:Diabetic Neuropathies / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D004817:Epidermis / Q000294:innervation* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007866:Leg; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D011115:Polyneuropathies / Q000473:pathology* / Q000503:physiopathology; D011446:Prospective Studies
D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human