Apart from its action on insulin sensitivity, hyperglycemia also exerts a direct negative effect on beta-cell function. Hyperglycemia-induced OS has been clearly indicated in deterioration of beta-cell function ; controlling OS either by using antioxidants or by overexpressing antioxidant enzymes restores beta-cell function. Biophysically, hyperglycemia generates reactive oxygen species in excess : it can therefore be expected that controlling hyperglycemia would improve an OS state of the cell as well. Thus, if oxidative stress is causally implicated in the development of beta-cell dysfunction and insulin resistance, then it ought to be useful to monitor oxidative stress in diabetic patients. In particular, if pathophysiological differences between individuals in the oxidative stress response to glycemic stress can be expressed quantitatively, that can potentially be useful in determining the extent of progress of the therapy, and adjusting an appropriate glycemic target for a patient. We have previously shown by measuring multiple biomarkers of OS serially across 8 weeks that OS improves concomitantly with lowering glucose in diabetic patients on treatment. Over twelve different biomarkers were studied, each of which improved with glucose control; of these glutathione appears to respond rapidly and in strong association with changes in glucose. Glutathione is an endogenous antioxidant and its thiol – disulphide redox couple is central to maintaining the redox environment of the cell. Glutathione is glucoxidized to glutathione disulfide in a number of reactions ; its essential ROS biochemistry is shown in Figure 1. Changes in GSH concentration influence half-cell reduction potential and therefore the cell with higher GSH concentration is more resistant to oxidative stress. It has been shown that a change in this redox couple is correlated with the biological status of the cell such as proliferation, differentiation and apoptosis. GSH is thus an excellent measure of oxidative stress in vivo. Its levels are depleted with OS in diabetes, and it recovers readily when glucose control is exercised.