Furthermore, in the Insulin Resistance and Atherosclerosis Study (IRAS), both baseline PAI-1 and its change over time predicted incident T2DM [33, 34], with higher PAI-1 predicting deterioration of insulin clearance over 5 years (a relationship not seen with other biomarkers including CRP, tumor necrosis factor-α, leptin and fibrinogen) [35]. This evidence concerns the gene TNF and atherosclerosis.