Prednisone is a medicine that is chemically similar to the natural hormone "cortisol." Prednisone and cortisol are both steroids. It is very common for prednisone to worsen diabetic control, because there are at least five ways by which it can raise the blood sugar.
The first way that prednisone raises your blood sugar is by triggering your liver to release sugar that has been stored away in your liver cells. Prednisone accomplishes this by causing an enzyme (protein) in the liver to become chemically active. This enzyme then breaks chemical bonds between sugars.
The second way that prednisone raises your blood sugar is by triggering your body to release small molecules that can be made into sugar. This process occurs because prednisone has effects on muscle and fat tissue. Prednisone is not the muscle-building type of steroid that is used by some people to artificially enhance muscle size. Instead, this kind of steroid causes certain muscles to thin or "waste," and it shifts fat distribution in some areas of the body. (Many people on high doses of prednisone develop a round face and a soft cushion of fat at the back of their neck, due to changes in where the body stores fat.) During a time that the body is reorganizing muscle or fat tissue, some of the building blocks for proteins and fats float freely in the bloodstream. These building blocks amino acids, fatty acids, and glycerol are freely available to your liver, which manipulates these raw ingredients chemically and produces glucose as a final product.
In addition to providing building blocks for sugar production (by acting on muscle and fat tissues), prednisone stimulates your liver to increase the chemical reactions that lead to new glucose production.
Prednisone interferes with the movement of glucose into your cells. This makes it harder for the insulin in your body to do its job, delivering glucose to your muscle and other tissues.
Finally, prednisone can increase your appetite. If prednisone causes you to eat more calories, then your diet can make your glucose control more challenging.
It is no wonder that prednisone can require someone with diabetes to use higher doses of treatment medicines!