title: Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes.
abstract: We sought to determine whether early nerve damage may be detected by corneal confocal microscopy (CCM), skin biopsy, and neurophysiological tests in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects. CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers (MNF) only. Intraepidermal nerve fiber density (IENFD) was assessed in skin specimens. Neurophysiological measures included nerve conduction studies (NCS), quantitative sensory testing (QST), and cardiovascular autonomic function tests (AFTs). Compared with control subjects, diabetic patients exhibited significantly reduced corneal nerve fiber length (CNFL-MNF), fiber density (CNFD-MNF), branch density (CNBD-MNF), connecting points (CNCP), IENFD, NCS, QST, and AFTs. CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21% and 14% of the diabetic patients, respectively. However, the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa. In conclusion, CCM and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes, but largely in different patients, suggesting a patchy manifestation pattern of small fiber neuropathy. Concomitant NCS impairment points to an early parallel involvement of small and large fibers, but the precise temporal sequence should be clarified in prospective studies.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, GermanyDepartment of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany dan.ziegler@ddz.uni-duesseldorf.de.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papanas
authors.affiliation: Department of Ophthalmology, University of Rostock, Rostock, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Zhivov
authors.affiliation: Institute for Applied Computer Science and Automation, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Allgeier
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Winter
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Ziegler
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Brüggemann
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.affiliation: Department of Ophthalmology, University of Rostock, Rostock, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Peschel
authors.affiliation: Institute for Applied Computer Science, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Köhler
authors.affiliation: Department of Ophthalmology, University of Rostock, Rostock, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stachs
authors.affiliation: Department of Ophthalmology, University of Rostock, Rostock, Germany.
authors.forename: Rudolf F
authors.initials: RF
authors.lastname: Guthoff
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, GermanyDepartment of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003315:Cornea / Q000473:pathology* / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D003929:Diabetic Neuropathies / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000473:pathology; D003941:Diagnostic Techniques, Ophthalmological; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology* / Q000648:ultrastructure; D012867:Skin / Q000473:pathology*; D055815:Young Adult