Corneal Confocal Microscopy Detects Neuropathy in Subjects With Impaired Glucose Tolerance

Omar Asghar; Ioannis N. Petropoulos; Uazman Alam; Wendy Jones; Maria Jeziorska; Andrew Marshall; Georgios Ponirakis; Hassan Fadavi; Andrew J.M. Boulton; Mitra Tavakoli; Rayaz A. Malik

Disclosures

Diabetes Care. 2014;37(9):2643-2646. 

In This Article

Results

Clinical Assessment

Subjects with IGT and control subjects were matched for age. Subjects with IGT had a significantly greater 2-h glucose level for the oral glucose tolerance test (9.2 ± 1.0 vs. 6.5 ± 0.6 mmol/L, P = 0.001), and they had a higher BMI (31.7 ± 1.0 vs. 27.9 ± 1.2 kg/m2, P = 0.02) and HbA1c (6.0 ± 0.2/43.9 ± 1.0 vs. 5.4 ± 0.1/36.0 ± 0.3 mmol/mol, P < 0.001), with a lower total (4.8 ± 0.2 vs. 5.5 ± 0.2 mmol/L, P = 0.02) and HDL (1.2 ± 0.1 vs. 1.7 ± 0.1 mmol/L, P < 0.001) cholesterol compared with control subjects. There was no difference in systolic/diastolic blood pressure (132/78 vs. 137/79 mmHg, P = 0.5), LDL cholesterol (2.1 ± 1.1 vs. 3.2 ± 0.6 mmol/L, P = 0.1), and triglycerides (2.8 ± 1.0 vs. 1.7 ± 0.9 mmol/L, P = 0.2).

Neuropathy Assessment

The neuropathy symptom profile (4.1 ± 1.0 vs. 0.5 ± 0.2, P < 0.001), the McGill pain index (2.8 ± 0.3 vs. 0.2 ± 0.1, P < 0.001), the neuropathy disability score (2.9 ± 0.5 vs. 0.6 ± 0.2, P = 0.001), VPT (15.9 ± 2.3 vs. 6.5 ± 1.1, P = 0.002), and WT (40.6 ± 0.8 vs. 37.6 ± 0.6, P = 0.006) were significantly increased, whereas CT (24.9 ± 1.3 vs. 27.5 ± 0.6, P = 0.03), neuropad response (71.0 ± 2.8% vs. 93.0 ± 5.6%, P = 0.05), IENFD (6.3 ± 0.6 vs. 9.1 ± 0.7, P = 0.03), CNFD (27.6 ± 1.2 vs. 37.4 ± 1.6, P < 0.001), CNBD (55.8 ± 6.0 vs. 89.2 ± 8.4, P = 0.02), and CNFL (22.1 ± 1.2 vs. 25.7 ± 1.2, P = 0.05) were significantly decreased in the IGT group compared with the control group (Fig. 1). There was no significant difference in sural sensory nerve amplitude (14.0 ± 1.4 vs. 16.6 ± 1.9, P = 0.2) and conduction velocity (49.9 ± 0.9 vs. 49.9 ± 1.0, P = 0.8), in peroneal motor nerve amplitude (4.6 ± 0.4 vs. 5.3 ± 0.5, P = 0.1) and conduction velocity (45.6 ± 0.7 vs. 47.5 ± 0.7, P = 0.1), or in HRVdb (9.5 ± 6.9 vs. 11.9 ± 6.9, P = 0.09).

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).

Under the assumption that CNFD is normally distributed in controls and IGT (Shapiro-Wilk W test, P > 0.05) and based on a cutoff point of 2 SD from the control average (CNFD = 24.0 no./mm2), subjects with IGT were restratified into two groups: 22 without IGT neuropathy (IGTN; CNFD >24.0 no./mm2) and 15 (40.5%) with IGTN (CNFD <24.0 no./mm2). There was significantly greater self-reported pain intensity (McGill Pain Index, P = 0.04) and reduction in CNBD (P = 0.02) and CNFL (P < 0.001) in subjects with IGTN compared with IGT (Fig. 1E).

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