Medical steroid use could push up diabetes risk

Glucocorticoids (GCs), or steroids, as they are popularly called, are often prescribed for their anti-inflammatory effects in a host of conditions including acute asthmatic attacks, allergies, and arthritis. However, are they doing good or harm?

A new study presented at The Society for Endocrinology Annual Conference shows that just one week of steroid use at doses similar to those routinely prescribed for inflammatory disorders can cause the body to develop metabolic disruptions that increase the risk of diabetes.

These drugs, also called glucocorticosteroids, are among the most highly prescribed drugs in conditions characterized by chronic and damaging inflammation or immune overactivity. They are also used as replacement therapy in adrenal insufficiency. About 2% to 3% of the UK population uses these drugs.

The researchers emphasize that the use of these powerful drugs must be regulated by an accurate knowledge of their potential long-term effects on the body. Otherwise, they say, patients on GCs could end up suffering debilitating long-term consequences.

The study and its findings

The current study was prompted by the need to find out the long-term health effects of short-term therapy with lower doses of GCs. The researchers used healthy men to test the metabolic effects of standard doses such as 10 mg or 15 mg of prednisolone, a GC in common use. After one week of using the GC, the participants were then checked for certain metabolic markers.

The results showed that fasting blood sugar levels remained unchanged, as did their weight and general health. However, there were more subtle signs of metabolic disruption. For instance, some metabolic markers showed the body was unable to regulate blood sugar as efficiently as before, which means they were at an increased risk of developing diabetes.

Where do glucocorticoids come from?

GCs and mineralocorticoids are two classes of hormones produced by the adrenal gland in the human body. They deal with the regulation of blood sugar and salts, respectively. They also have many other roles. In particular, GCs have powerful anti-inflammatory properties, and also suppress the immune system.

In humans, cortisol is the archetypal GC. When it binds to a cytoplasmic receptor, it brings about a series of changes in gene expression which causes the production of a variety of proteins. GCs act on about a third of human genes, which is probably why they have such an immense impact on the body. Almost all cells have GC receptors.

Effects on blood sugar

GCs have several different effects on blood glucose:

• They stimulate the production of glucose in the liver from non-sugar chemicals like amino acids and fats
• They enhance the supply of amino acids from other parts of the body to the liver, to produce more glucose
• They suppress glucose entry into muscle and fat cells
• They encourage fat cells to release free fatty acids which become alternative energy sources in muscle cells, as well as glycerol which can be used to produce more glucose

Effects on inflammation

GCs bind with their receptors to regulate gene expression and thus reduce the secretion of many chemicals that take part in the inflammation cascade. This puts an end to the inflammatory process for the duration of the action of the drug.

Other effects

GCs also affect bone development, brain processes, heart health, reproduction, and fetal development.

Side effects

Due to the diversity of their actions and the vast reach of their activity, GCs are notorious for their metabolic effects on many body systems, including increases in blood sugar and body fat, when they are used at high doses or for long periods. At the same time, nobody quite knew what happened to the body when standard doses were used in the therapy of these inflammatory or autoimmune disorders.

Implications

The researchers say their findings show the need to determine which dosage level is required to balance the known effectiveness of these drugs in inflammation with the need to minimize their negative side-effects on the body. In addition, they emphasize that doctors should become more alert when they prescribe these drugs even in small doses, or for short periods, and should watch their patients for signs that they are causing negative health impacts.

Researcher Riccardo Pofi says, “This is the first study to examine the very short-term metabolic effects of commonly prescribed doses of glucocorticoids on healthy men and indicates that, even at these lower doses, glucose metabolism is impaired suggesting an increased risk of diabetes with continued treatment.” He goes on to suggest, “We need to more accurately assess GC use in patients to prevent and reduce the undesired effects, especially in patients for which steroid treatment is essential for life.”

Studies on larger numbers of people will now be required to confirm the results, as well as to uncover the mechanism through which these changes occur. The researchers now want to look into what happens when patients take GCs in combination with drugs for diabetes so that they can understand whether this helps to prevent the undesirable side-effects of GCs on blood sugar regulation, or at least to reduce their severity.

Journal reference:

Riccardo Pofi, Ilaria Bonaventura, Nanthia Othonos, Thomas Marjot, Ahmed Moolla, Andrea M Isidori, Leanne Hodson & Jeremy W Tomlinson, Glucocorticoid treatment is associated with dose-dependent effects in healthy male volunteers, Endocrine Abstracts (2019) 65 P242 | DOI: 10.1530/endoabs.65.P242, https://www.endocrine-abstracts.org/ea/0065/ea0065p242.htm