NR3C1 and Hyperglycemia: On the other hand, long-term hyperglycaemia may lead to a glucocorticoid-resistant status in the hypothalamus–pituitary–adrenal axis by increasing the ROS and oxidative stress, which may damage the glucocorticoid receptor function that further blunts the axis response and causes reactive hypercortisolism in T2DM [126,127].