What is the main effect of glucocorticoids (GCs) on carbohydrate metabolism?

From the Guidelines

The main effect of glucocorticoids on carbohydrate metabolism is to increase blood glucose levels through multiple mechanisms, including stimulating gluconeogenesis, promoting glycogenolysis, and inducing insulin resistance, as evident in the most recent study from 2025 1.

Mechanisms of Glucocorticoids on Carbohydrate Metabolism

The effects of glucocorticoids on carbohydrate metabolism are multifaceted:

• They stimulate gluconeogenesis in the liver, which is the production of new glucose from non-carbohydrate sources such as amino acids.
• They promote glycogenolysis, the breakdown of glycogen stores to release glucose.
• They decrease glucose uptake and utilization in peripheral tissues like muscle and fat by inducing insulin resistance, which occurs through downregulation of glucose transporters (particularly GLUT4) and interference with insulin signaling pathways.
• They increase protein catabolism in muscle, providing amino acids as substrates for gluconeogenesis.

Clinical Implications

These combined actions serve a physiological purpose during stress, when the body needs to ensure adequate glucose supply to vital organs, particularly the brain. However, in clinical settings, these effects can lead to hyperglycemia, which explains why patients on glucocorticoid therapy (such as prednisone, dexamethasone, or hydrocortisone) often develop steroid-induced diabetes, especially with long-term use or high doses, as highlighted in studies from 2023 1, 2024 1, and 2022 1.

Management Considerations

Given the potential for glucocorticoids to induce hyperglycemia, it is crucial to monitor blood glucose levels closely in patients receiving these medications, and to adjust insulin treatments accordingly, as discussed in the 2025 study 1. The type and duration of action of the glucocorticoid, as well as the patient's preexisting diabetes status, should be considered when determining the appropriate insulin regimen.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

The main effect of glucocorticoids (GCs) on carbohydrate metabolism is not explicitly stated in the provided text. However, it is mentioned that glucocorticoids cause profound and varied metabolic effects.

• The label does mention that glucocorticoids have an impact on metabolism, but it does not specify the exact effect on carbohydrate metabolism 2.

From the Research

Main Effects of Glucocorticoids on Carbohydrate Metabolism

• Glucocorticoids affect glucose metabolism by decreasing glucose utilization and increasing hepatic glucose production 3
• They increase the stocks of carbohydrate and the supra-hepatic flow of glucose, producing a centripetal redistribution of adipose stocks and potentiating adipocyte lipolysis 4
• Glucocorticoids counteract insulin by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis, inducing insulin resistance (IR) 5
• They regulate glucose homeostasis by promoting gluconeogenesis in the liver, decreasing glucose uptake and utilization in skeletal muscle and white adipose tissue, and regulating glycogen metabolism 6

Mechanisms of Glucocorticoid Action

• Glucocorticoids may attenuate the incretin effect and have a direct impact on beta-cell function, although the mechanism is not fully defined 5
• They can impair insulin signaling, resulting in reduced glucose disposal and augmented endogenous glucose production, leading to peripheral insulin resistance (IR) 7
• Glucocorticoids can also promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue, contributing to glucose homeostasis disruption 7

Effects on Pancreatic Function

• Glucocorticoids can modulate the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin 6
• They can induce hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia 7
• The release of other islet hormones, such as somatostatin, amylin, and ghrelin, is also affected by glucocorticoid administration 7