Therapeutic strategies for diabetes and complications: a role for sphingolipids?

Diabetes is a debilitating chronic disease that has no cure and can only be managed by pharmaceutical or nutritional interventions. Worldwide, the incidence of diabetes and diabetic complications is dramatically increasing. This may reflect the incomplete knowledge base underlying the role of inflammatory or nutritional stresses to exacerbate diabetic complications. Despite the knowledge that hyperlipidemia is a cardinal feature of both Type 1 and 2 diabetes, the actual lipid species that contribute to complications such as diabetic nephropathy, retinopathy, neuropathy and cardiovascular disease have not been well defined, or have not elucidated new treatment strategies. Sphingolipids comprise only a fraction of total lipids but a body of evidence has now identified dysfunctional sphingolipid metabolism and/or generation of specific sphingolipid metabolites as contributors to diabetic complications. This review suggests that pharmacological therapies that target dysfunctional sphingolipid metabolism and/or signaling may prove beneficial in decreasing the chronic pathology of hyperglycemia and hyperlipidemia. Moreover, the review suggests that these treatment options may also prove beneficial to ameliorate or delay pancreatic beta cell failure.