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


Diabetes Care. 2014;37(9):2643-2646. 

In This Article


A recent study has shown a significant reduction in IENFD and abnormal corneal nerve morphology in patients with type 2 diabetes of short duration, suggesting that neuropathy may be an early complication,[10] and of course, longitudinal data from the Rochester cohort[11] suggest that duration and severity of exposure to hyperglycemia are related to the severity of neuropathy. In the current study, we show a significant increase in neuropathic symptoms, consistent with the MONICA/KORA Augsburg Surveys,[3] which also found a threefold increase in neuropathic pain in subjects with IGT. We also show a significant alteration in sudomotor function, whereas cardiac autonomic function and electrophysiology were normal, similar to a previous study in subjects with IGT demonstrating an abnormal sympathetic skin response but normal results on electrophysiology and standard autonomic function tests.[12] These latter findings are similar to a large population-based study that also showed no electrodiagnostic abnormalities in subjects with impaired fasting glucose or IGT.[4] However, we demonstrate a significant abnormality in VPT, WT, and CT, similar to the San Luis Valley study,[2] which also reported impaired VPT in 11.2% of subjects with IGT compared with 3.5% in control subjects.

Previous studies have demonstrated a reduction in IENFD in subjects with IGT, which improved after lifestyle intervention,[5] suggesting that this early abnormality may be amenable to treatment. We now confirm a significant reduction in IENFD in subjects with IGT. In addition, we also demonstrate a significant abnormality in corneal nerve morphology using the noninvasive technique of CCM and indeed show that 40.5% of subjects with IGT have significant small-fiber damage based on CNFD reduction. CCM provides a unique opportunity to noninvasively and rapidly assess unmyelinated C fibers in vivo, which has important diagnostic[6] and prognostic[8] implications. In conclusion, this study shows evidence of neuropathy in subjects with IGT, as evidenced by abnormal symptoms, signs, quantitative sensory testing, skin biopsy, and CCM, but not neurophysiology.[13]