Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Aug;38(8):1502-8.
doi: 10.2337/dc14-2733. Epub 2015 Apr 15.

Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes

Shazli Azmi  1 , Maryam Ferdousi  1 , Ioannis N Petropoulos  2 , Georgios Ponirakis  2 , Uazman Alam  1 , Hassan Fadavi  1 , Omar Asghar  1 , Andrew Marshall  3 , Andrew J Atkinson  1 , Wendy Jones  1 , Andrew J M Boulton  1 , Mitra Tavakoli  1 , Maria Jeziorska  1 , Rayaz A Malik  4
Affiliations

Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes

Shazli Azmi et al. Diabetes Care. 2015 Aug.

Abstract

Objective: Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management.

Research design and methods: Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years.

Results: Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years.

Conclusions: CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Corneal confocal images from control subject at baseline (A), control subject at follow-up (B), IGT subject who developed type 2 diabetes at baseline (C), IGT subject who developed type 2 diabetes at follow-up (D), IGT subject who remained IGT at baseline (E), IGT subject who remained IGT at follow-up (F), IGT subject who reverted to NGT at baseline (G), and IGT subject who reverted to NGT at follow-up (H). Red arrow, corneal nerve fiber; yellow arrow, corneal nerve branch.
Figure 2
Figure 2
Change in corneal nerve fiber morphological parameters in subjects at baseline (black) and 36 months (red).
See this image and copyright information in PMC

References

    1. Aguiree F, Brown A, Cho NH, Dahlquist G, Dodd S, Dunning T, et al. IDF Diabetes Atlas. 2013
    1. Yudkin JS, Montori VM. The epidemic of pre-diabetes: the medicine and the politics. BMJ 2014;349:g4485. - PMC - PubMed
    1. Edelstein SL, Knowler WC, Bain RP, et al. Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies. Diabetes 1997;46:701–710 - PMC - PubMed
    1. Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes 2003;52:2867–2873 - PubMed
    1. Manley S, Meyer L, Neil H, Ross I, Turner R, Holman R. UK Prospective Diabetes Study 6. Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diabetes Res 1990;13:1–11 - PubMed

Publication types

MeSH terms