Ziegler Dan, Strom Alexander, Brüggemann Jutta, Ziegler Iris, Ringel Bernd, Püttgen Sonja, Roden Michael
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany,
Diabetologia. 2015 Jul;58(7):1621-5. doi: 10.1007/s00125-015-3609-5. Epub 2015 May 2.
AIMS/HYPOTHESIS: 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.
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.
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/INTERPRETATION: 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.
目的/假设：氧化应激和微血管损伤与糖尿病神经病变的发病机制有关，线粒体中超氧化物解毒由锰超氧化物歧化酶2（SOD2）负责。我们假设，新诊断的2型糖尿病患者的皮肤SOD2表达和内皮细胞面积会发生改变。
在这项横断面研究中，我们对德国糖尿病研究中的69例新诊断的2型糖尿病参与者和51例对照个体进行了皮肤活检免疫组化评估、外周神经功能和心率变异性评估。
与对照组相比，糖尿病组小腿远端表皮下SOD2面积增加了约60%（0.24±0.02%对0.15±0.02%；p=0.0005），且与糖尿病病程延长（r=0.271；p=0.024）以及作为交感迷走神经平衡指标的低频/高频比值相关（β=0.381；p=0.002）。两组之间表皮下内皮细胞面积（通过CD31染色测量）无差异。
结论/解读：在新诊断的2型糖尿病个体中，皮肤抗氧化防御能力随着糖尿病病程的延长而增强，且与心脏交感迷走神经失衡导致交感神经占优势有关，而无内皮细胞损伤证据。皮肤SOD2水平是否能预测糖尿病神经病变的发生仍有待前瞻性研究确定。
