Deoxysphingoid Lipids in Diabetes and Diabetic Polyneuropathy

Diabetes is the leading cause of neuropathy in the developed world and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes patients (WHO 2009). We recently discovered the accumulation of deoxysphingoid lipids (dSL) in an inherited polyneuropathy (HSN1, hereditary sensory neuropathy type 1) with features very similar to that of diabetic polyneuropathy. In the inherited disorder, the enzyme serine palmitoyl-transferase (SPT) loses affinity for serine and takes up other amino acids, such as alanine. This results in the formation of an atypical class of lipids (dSL) that have been shown to be toxic. Recently we also found these dSL elevated in patients with diabetes (Bertea et al. 2010), thereby elucidating a common pathway in the degeneration of peripheral nerve.