Pronounced reduction of cutaneous Langerhans cell density in recently diagnosed type 2 diabetes
- Alexander Strom1,
- Jutta Brüggemann1,
- Iris Ziegler1,
- Kay Jeruschke2,
- Juergen Weiss2,
- Hadi Al-Hasani2,
- Michael Roden1,3,*⇑,
- Dan Ziegler1,3,*⇑,
- for the GDS Group**
- 1Institute for Clinical Diabetology and the
- 2Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany;
- 3Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
- Corresponding authors: Dan Ziegler, Email: or Michael Roden, Email:
Immune-mediated processes have been implicated in the pathogenesis of diabetic polyneuropathy. Langerhans cells (LCs) are the sole dendritic cell type located in the healthy epidermis and exert tolerogenic immune functions. We aimed to determine whether alterations in cutaneous LC density and intraepidermal nerve fiber density (IENFD) are present in patients with recently diagnosed type 2 diabetes. Skin biopsies from the distal leg from 96 type 2 diabetic patients and 75 healthy controls were used for quantification of LC density and IENFD. LCs and IENFs were labeled using immunohistochemistry. Nerve conduction studies, quantitative sensory testing, and neurological examination were used to assess peripheral nerve function. LC density was markedly reduced in the diabetes compared to the control group, but did not correlate with reduced IENFD or peripheral nerve function. Multivariate linear regression analysis revealed a strong association between LC density and whole-body insulin sensitivity in women but not men with diabetes. Prospective studies should establish whether the pronounced reduction of cutaneous Langerhans cells detected in recently diagnosed type 2 diabetes could promote a cutaneous immunogenic imbalance towards inflammation predisposing to polyneuropathy and foot ulcers.
* M.R. and D.Z. share senior authorship.
** The GDS Group consists of H. Al-Hasani, J. Eckel, G. Giani, C. Herder, A. Icks, J. Kotzka, K. Müssig, B. Nowotny, P. J. Nowotny, W. Rathmann, J. Rosenbauer, P. Schadewaldt, J. Szendroedi, D. Ziegler, and M. Roden (speaker)
- Received September 18, 2013.
- Accepted December 2, 2014.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.