Overexpression of cutaneous mitochondrial superoxide dismutase in recent-onset type 2 diabetes.
OBJECTIVE
Oxidative stress and microvascular damage have been implicated in the pathogenesis of diabetic neuropathy, with manganese superoxide dismutase 2 (SOD2) responsible for superoxide detoxification in mitochondria. We hypothesised that patients with recently diagnosed type 2 diabetes would show an altered cutaneous expression of SOD2 and endothelial cell area.


METHODS
In this cross-sectional study, we assessed skin biopsies using immunohistochemistry, peripheral nerve function and heart rate variability in 69 participants of the German Diabetes Study with recently diagnosed type 2 diabetes and 51 control individuals.


RESULTS
Subepidermal SOD2 area in the distal leg was increased by ~60% in the diabetic group vs the controls (0.24 ± 0.02% vs 0.15 ± 0.02%; p = 0.0005) and was correlated with an increasing duration of diabetes (r = 0.271; p = 0.024) and with the low frequency/high frequency ratio (β = 0.381; p = 0.002) as an indicator of sympathovagal balance. The area of the subepidermal endothelial cells (measured by CD31 staining) did not differ between the groups.


CONCLUSIONS
Cutaneous antioxidative defence is enhanced in relation to the duration of diabetes and is linked to a cardiac sympathovagal imbalance towards a sympathetic predominance in individuals with recently diagnosed type 2 diabetes without evidence of endothelial cell damage. Whether cutaneous SOD2 levels can predict the development of diabetic neuropathy remains to be determined in prospective studies.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany, dan.ziegler@ddz.uni-duesseldorf.de.
Dan
D
Ziegler
Alexander
A
Strom
Jutta
J
Brüggemann
Iris
I
Ziegler
Bernd
B
Ringel
Sonja
S
Püttgen
Michael
M
Roden
D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000503:physiopathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011446:Prospective Studies; D012867:Skin / Q000201:enzymology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology; D000099156:Superoxide Dismutase 2
D006442:Glycated Hemoglobin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2