To develop a new strategy to identify acquired demyelination in diabetic distal symmetric polyneuropathy (DSP).

Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds what is expected from pure axonal loss and can be attributed to additional acquired demyelination.

We prospectively studied CV and urine secretory phospholipase A2 (sPLA2) activity in 90 diabetic DSP patients divided into 2 groups A and B with and without at least one motor nerve with CV slowing in the demyelination range by AAN criteria. sPLA2 activity was tested in 46 healthy controls. In parallel, we studied CV in these diabetic patients using a regression analysis that we developed and validated from data from 114 CIDP patients. 

Mean urine sPLA2 activity was significantly higher in diabetic groups compared to healthy controls, (942.9 ± 977.97 vs. 591.6 ± 390.15, pmol/min/ml p < 0.05), and was significantly higher in group A compared to B, (1328.3 ± 1274.21 vs. 673.8 ± 576.93 pmol/min/ml, p = 0.0014). The number of patients with elevated sPLA2 activity and have more than 2 motor nerves with CV slowing in the AAN or regression analysis ranges was significantly higher in patients of group A compared to group B (35.1% vs. 5.7%, p = 0.0005). Furthermore, 13.5% in diabetic DSP group A and no patient in diabetic DSP group B fulfilled an additional criteria of more than one motor nerve with CV slowing in the demyelinating range with the corresponding F response in the demyelinating range by AAN criteria.

To the best of our knowledge, the present study is the first to use a combination of regression analysis of electrodiagnostic data and a urine biological marker of inflammation to identify a subgroup of diabetic DSP with significant contribution of acquired demyelination and neuroinflammation in diabetic nerve injury.