Effect of Glycemic Control on Sudomotor Denervation in Type 2 Diabetes
- Kai-Ren Luo, MS1,
- Chi-Chao Chao, MD, PHD2,
- Paul-Chen Hsieh, BS3,
- June-Horng Lue, PHD1⇓ and
- Sung-Tsang Hsieh, MD, PHD1,2⇓
- 1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
- 2Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
- 3Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Corresponding authors: Sung-Tsang Hsieh, , and June-Horng Lue, .
K.-R.L. and C.-C.C. contributed equally to this study.
OBJECTIVE Sudomotor symptoms are a common component of diabetic autonomic neuropathy, but the pathology of sudomotor innervation and its relationship with glycemic control have remained obscured.
RESEARCH DESIGN AND METHODS We enrolled 42 patients (26 males and 16 females aged 56.64 ± 12.67 years) with diabetic neuropathy defined by symmetric distally predominant sensory symptoms, abnormal nerve conduction studies, and reduced intraepidermal nerve fiber density in the leg. Skin biopsies of the distal leg were immunostained with antiprotein gene product 9.5 for nerve fibers and counterstained with Congo red for sweat glands. Sweat gland innervation index (SGII) was quantified with a new computerized area-based morphometric system.
RESULTS Protein gene product 9.5(+) nerve terminals surrounded secretory coils of the sweat glands in the skin of control subjects. Sudomotor denervation was present in diabetic patients, manifesting as depletion of periglandular nerve fibers with lower SGII compared with 42 age- and sex-matched control subjects (2.54 ± 1.87 vs. 4.68 ± 1.51%, P < 0.001). The SGII was correlated with HbA1c (P = 0.011) and was lower in patients with anhidrosis of the feet compared with those with normal sweating of the feet (0.82 ± 0.69 vs. 3.00 ± 1.81%, P = 0.001). Sudomotor denervation was concordant with cardiac autonomic dysfunction as assessed with reduced heart rate variability (P = 0.003).
CONCLUSIONS Sudomotor denervation is a significant presentation of diabetic neuropathy, and the SGII was associated with HbA1c. A skin biopsy offers a structural assessment of sudomotor innervation.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1607/-/DC1.
- Received August 23, 2011.
- Accepted November 16, 2011.
- © 2012 by the American Diabetes Association.
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