Intraepidermal nerve fiber density as a marker of early diabetic neuropathy

Abstract

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications.

Small fibre dysfunction, microvascular complications and glycaemic control in type 1 diabetes: a case–control study

“…Indeed, an inverse relationship between age and intraepidermal nerve fibre density has been previously described [18,19]; the influence of sex, height, weight and BMI is less certain [18,20,21].…”

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

“…However, the abnormalities are not as extensive as in patients with classical disease (Biegstraaten et al 2011(Biegstraaten et al , 2012 and predominantly concern small nerve fibre structure as represented by the IENFD. Similarly, in patients with diabetes mellitus (DM), an abnormal IENFD in the distal leg and impaired cold sensation have been found, even without neuropathic symptoms (Umapathi et al 2007;Loseth et al 2008;Ragé et al 2011). For both DM and nonclassical FD, it may be hypothesized that a reduced IENFD and abnormal QST modalities reflect a presymptomatic state.…”

Confocal retinal microscopy - the new non-invasive method for diagnostics of the early manifestations of the lesions in the peripheral nervous system associated with diabetes mellitus

“…К патоморфологическим методам относятся био-псия нерва [18,19] и определение плотности эпи-дермальных нервных волокон в биоптатах кожи [20,21]. Оба метода являются инвазивными и, соответ-ственно, сопряжены с риском инфекционных ос-ложнений.…”