Early Detection of Nerve Fiber Loss by Corneal Confocal Microscopy and Skin Biopsy in Recently Diagnosed Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 63; no. 7; pp. 2454 - 2463
• Main Authors: ZIEGLER, Dan, PAPANAS, Nikolaos, STACHS, Oliver, GUTHOFF, Rudolf F, RODEN, Michael, ZHIVOV, Andrey, ALLGEIER, Stephan, WINTER, Karsten, ZIEGLER, Iris, BRÜGGEMANN, Jutta, STROM, Alexander, PESCHEL, Sabine, KÖHLER, Bernd
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2014
• Subjects: Adolescent; Adult; Aged; Algorithms; Biological and medical sciences; Biopsy; Case-Control Studies; Cornea - pathology; Cornea - ultrastructure; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - pathology; Diabetic Retinopathy - diagnosis; Diabetic Retinopathy - pathology; Diagnostic Techniques, Ophthalmological; Early Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Male; Medical diagnosis; Medical sciences; Microscopy, Confocal - methods; Middle Aged; Nerve Fibers - pathology; Nerve Fibers - ultrastructure; Skin; Skin - pathology; Young Adult; Endocrinopathy; Type 2 diabetes; Biopsy; Metabolic diseases; Confocal microscopy; Skin; Nerve fiber
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db13-1819

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.