First, sphingomyelin and other metabolites of the sphingolipid pathway have been shown to play a causal role in the development of insulin resistance by inhibition of several intermediates in the insulin signalling pathway, including insulin receptor substrate 1, Akt/PKB and phosphoinositide 3-kinase [31–33], whereby insulin resistance is a well-accepted mechanism promoting both microvascular and macrovascular damage [34, 35]. Here, IRS1 is linked to Insulin resistance.