HMOX1 and diabetes mellitus: Interestingly, a study that evaluated tumor necrosis factor-alpha (TNF-α), Nrf2, and HO-1 levels in normal glucose tolerance, patients with pre-DM, and T2DM found that TNF-α increased Nrf2 and HO-1 decreased as patients became more diabetic, suggesting that, along with aggravation of oxidative stress and inflammatory response, Nrf2 activation and HO-1 expression were both inhibited [128].