Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance

Abstract

Objective: Impaired glucose tolerance (IGT) represents one of the earliest stages of glucose dysregulation and is associated with macrovascular disease, retinopathy, and microalbuminuria, but whether IGT causes neuropathy is unclear.

Research design and methods: Thirty-seven subjects with IGT and 20 age-matched control subjects underwent a comprehensive evaluation of neuropathy by assessing symptoms, neurological deficits, nerve conduction studies, quantitative sensory testing, heart rate variability deep breathing (HRVdb), skin biopsy, and corneal confocal microscopy (CCM).

Results: Subjects with IGT had a significantly increased neuropathy symptom profile (P < 0.001), McGill pain index (P < 0.001), neuropathy disability score (P = 0.001), vibration perception threshold (P = 0.002), warm threshold (P = 0.006), and cool threshold (P = 0.03), with a reduction in intraepidermal nerve fiber density (P = 0.03), corneal nerve fiber density (P < 0.001), corneal nerve branch density (P = 0.002), and corneal nerve fiber length (P = 0.05). No significant difference was found in sensory and motor nerve amplitude and conduction velocity or HRVdb.

Conclusions: Subjects with IGT have evidence of neuropathy, particularly small-fiber damage, which can be detected using skin biopsy and CCM.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Skin punch biopsy specimens immunostained for PGP9.5 (A and B) and CCM images (C and D) from a healthy control subject vs. a subject with IGT. The graphs show the distribution of CNFD (E), CNBD (F), and CNFL (G) in control subjects vs. IGT subjects. In C compared with D, a significant reduction in corneal nerve fibers (yellow arrows) and nerve branches (red arrows) is observed, which mirrors the reduction in the same subject in intraepidermal nerve fibers (yellow arrows) reaching the upper levels of epidermis in B compared with A. The subepidermal nerve plexus is also visible (purple arrowhead). Data points in E, F, and G represent actual corneal subbasal nerve parameters in control subjects (n = 20) vs. IGT subjects (n = 37). The purple dashed lines represent group averages, and the blue dashed line in E represents a cutoff for “risk of neuropathy” (IGTN).