title: Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes.
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.
  
  
  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.
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Shazli
authors: S
authors: Azmi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Maryam
authors: M
authors: Ferdousi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K. Weill-Cornell Medical College, Doha, Qatar.
authors: Ioannis N
authors: IN
authors: Petropoulos
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K. Weill-Cornell Medical College, Doha, Qatar.
authors: Georgios
authors: G
authors: Ponirakis
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Uazman
authors: U
authors: Alam
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Hassan
authors: H
authors: Fadavi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Omar
authors: O
authors: Asghar
authors: Department of Clinical Neurophysiology, Central Manchester NHS Foundation Trust, Manchester, U.K.
authors: Andrew
authors: A
authors: Marshall
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Andrew J
authors: AJ
authors: Atkinson
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Wendy
authors: W
authors: Jones
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Andrew J M
authors: AJ
authors: Boulton
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Mitra
authors: M
authors: Tavakoli
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors: Maria
authors: M
authors: Jeziorska
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K. Weill-Cornell Medical College, Doha, Qatar ram2045@qatar-med.cornell.edu rayaz.a.malik@manchester.ac.uk.
authors: Rayaz A
authors: RA
authors: Malik
mesh_terms: D001707:Biopsy, Needle; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003315:Cornea / Q000294:innervation* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D004916:Erythromelalgia / Q000473:pathology*; D005260:Female; D018149:Glucose Intolerance / Q000473:pathology; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D011236:Prediabetic State / Q000473:pathology; D011446:Prospective Studies; D012867:Skin / Q000294:innervation / Q000473:pathology*
chemical_list: D001786:Blood Glucose