title: Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria.
abstract: OBJECTIVE
  Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.
  
  
  METHODS
  All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)].
  
  
  RESULTS
  53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.
  
  
  CONCLUSIONS
  IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Weill Cornell Medical College Qatar, Division of Research, Qatar Foundation, Education City, 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 System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Patrick
authors: P
authors: Green
authors: Queen Mary's University, Bart's and London National Health System Trust, London, United Kingdom.
authors: Agnes W S
authors: AW
authors: Chan
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Uazman
authors: U
authors: Alam
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Hassan
authors: H
authors: Fadavi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Andrew
authors: A
authors: Marshall
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Omar
authors: O
authors: Asghar
authors: Institute of Health and Biomedical Innovation and School of Optometry and Vision Science, Queensland University of Technology, Brisbane, Australia.
authors: Nathan
authors: N
authors: Efron
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Mitra
authors: M
authors: Tavakoli
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health System Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Weill Cornell Medical College Qatar, Division of Research, Qatar Foundation, Education City, Doha, Qatar.
authors: Rayaz A
authors: RA
authors: Malik
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000473:pathology; D003315:Cornea / Q000473:pathology / Q000648:ultrastructure*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology / Q000648:ultrastructure