Lower serum extracellular superoxide dismutase levels are associated with polyneuropathy in recent-onset diabetes

Abstract

Increased oxidative stress is implicated in the pathogenesis of experimental diabetic neuropathy, but translational evidence in recent-onset diabetes is scarce. We aimed to determine whether markers of systemic oxidative stress are associated with diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. In this cross-sectional study, we measured serum concentrations of extracellular superoxide dismutase (SOD3), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) in 107 type 1 and 215 type 2 diabetes patients from the German Diabetes Study baseline cohort and 37 glucose-tolerant individuals (controls). DSPN was defined by electrophysiological and clinical criteria (Toronto Consensus, 2011). SOD3 and GSH concentrations were lower in individuals with type 1 and type 2 diabetes compared with concentrations in controls (P<0.0001). In contrast, the TBARS concentration was higher in participants with type 1 diabetes and type 2 diabetes compared with levels in controls (P<0.0001). In addition, the SOD3 concentration was higher in participants with type 1 diabetes compared to concentrations in those with type 2 diabetes (P<0.0001). A low SOD3 concentration was associated with DSPN in individuals with type 1 diabetes (β=−0.306, P=0.002), type 2 diabetes (β=−0.164, P=0.017), and in both groups combined (β=−0.206, P=0.0003). Lower SOD3 concentrations were associated with decreased motor nerve conduction velocity (NCV) in men and, to a lesser degree, with reduced sensory NCV in women with diabetes. In conclusion, several biomarkers of oxidative stress are altered in recent-onset diabetes, with only a lower SOD3 concentration being linked to the presence of DSPN, suggesting a role for reduced extracellular antioxidative defense against superoxide in the early development of DSPN.

Myeloperoxidase, superoxide dismutase‐3, cardiometabolic risk factors, and distal sensorimotor polyneuropathy: The KORA F4/FF4 study

“…The discrepancy between the first of the aforementioned studies and our study cannot be explained by technical factors, as both studies used the same assay for quantification of SOD3 and also similar preanalytical procedures. However, the other study was based on a much younger study sample and lacked a population‐based design, so that selection bias cannot be excluded.…”

“…Based on 2 previous observations, we had expected associations in the opposite direction. The first study found that SOD3 levels were lower in individuals with recent‐onset type 2 diabetes compared with nondiabetic individuals and in diabetes patients with DSPN compared with DSPN‐free diabetes patients . The second study reported that gene variants that were linked to higher SOD3 levels had a protective effect on the risk for cardiovascular events in patients with diabetes .…”

“…Lower systemic SOD3 levels were observed in people with type 2 diabetes and DSPN, and gene variants associated with lower SOD3 levels were related to higher cardiovascular risk. 21,22 We hypothesized that higher serum MPO and lower serum SOD3 are associated with the development of DSPN independently of cardiometabolic risk factors. Therefore, we aimed to assess whether both biomarkers of oxidative stress are associated with prevalent and incident DSPN in a large population-based cohort.…”

“…Extracellular superoxide dismutase (SOD3) is the major antioxidant enzyme in the circulation catalyzing the dismutation of superoxide radicals (O 2 − ). Lower systemic SOD3 levels were observed in people with type 2 diabetes and DSPN, and gene variants associated with lower SOD3 levels were related to higher cardiovascular risk …”

Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy

“…The exact pathogenesis is complex and oxidative stress has a significant role in the pathogenesis of DN and its progression to ESRD. In recent years, a variety of biomarkers of oxidative stress associated with DN has been found and the most important ones used in clinical studies are presented ( Table 2 ) [ 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ].…”