| Abstract: | Insulin resistance is now acknowledged to be a significant predictor of cardiovascular morbidity and mortality as well as the primary defect in Type 2 diabetes. Such pathologies are set to pose an ever greater socio-economic burden in developed and developing nations, especially in the light of evidence that insulin resistance may be acquired through the (Western) diet. Given the recognition of the central role of insulin resistance in the progression of syndrome X and diabetes, improving insulin sensitivity has become a major clinical focus. The traditional ‘first line of defence’ approach to restoring glycaemic control in diabetes involving dietary and exercise regimens, may now be supplemented with insulin-sensitising pharmacotherapy. This therapeutic modality, which was clinically pioneered with the biguanide metformin, is also today provided by the thiazolidinedione (TZD) class of anti-hyperglycaemic agent, exemplified by rosiglitazone and pioglitazone. More TZD derivatives are to be expected, along with novel, non-TZD ligands of their common therapeutic target: the peroxisome proliferator-activated receptor-γ (PPARγ). In addition, the role of PPARα activation in the regulation of insulin sensitivity is gaining attention. There is also the theoretical prospect at least of creating a therapeutic synergy by co-administering retinoid X receptor (RXR) agonists or so-called rexinoids with these PPAR ligands. Furthermore, interest has been registered in a nutraceutical approach to insulin resistance concerning supranutritional levels of chromium and biotin. While TZDs are currently only licensed for use in established Type 2 diabetes, such insulin-sensitising interventions have the potential to delay or prevent both cardiovascular and diabetic disease progression in insulin resistant individuals. |
