Insulin resistance as a proinflammatory state: mechanisms, mediators, and therapeutic interventions

Abstract

Insulin resistance has been recognized as an inflammatory disease based on the scientific evidence collected over the last decade. Inflammatory markers like CRP, PAI-1, IL-6 are present in higher concentrations in insulin resistant people than in normal people. Mechanisms, linking inflammation to insulin resistance are being explored and progress has been made in this direction. TNFalpha has been shown to be responsible for insulin resistance in obese subjects. Macronutrient intake may also induce inflammation whereas fasting has anti-inflammatory effects. Insulin itself has been found to be anti-inflammatory and this action may be useful in many disease states. Thiazolidinediones, such as rosiglitazone that act primarily as insulin sensitisers, have a profound anti-inflammatory and potentially antiatherosclerotic activity. These effects may be of considerable clinical significance if sustained during long-term therapy, given the morbidity and mortality associated with atherosclerosis, the major complication of insulin resistance.