From the Guidelines
The main effect of glucocorticoids on carbohydrate metabolism is to increase blood glucose levels through multiple mechanisms, including promoting gluconeogenesis, reducing glucose uptake and utilization in peripheral tissues, and inducing insulin resistance, as evident in studies such as 1.
Key Mechanisms
The effects of glucocorticoids on carbohydrate metabolism can be broken down into several key mechanisms:
- Promoting gluconeogenesis in the liver, which is the production of new glucose from non-carbohydrate sources like amino acids.
- Reducing glucose uptake and utilization in peripheral tissues, particularly muscle and adipose tissue, by inducing insulin resistance.
- Stimulating glycogen synthesis in the liver while promoting protein catabolism in muscle, which releases amino acids that serve as substrates for gluconeogenesis.
- Enhancing the effects of other glucose-raising hormones like glucagon and epinephrine.
Clinical Implications
These metabolic actions explain why chronic glucocorticoid therapy often leads to hyperglycemia, and why patients with Cushing's syndrome (characterized by excess cortisol) frequently develop diabetes mellitus. For patients receiving glucocorticoid therapy, blood glucose monitoring is essential, particularly in those with pre-existing diabetes or risk factors for diabetes, as highlighted in 2 and 3. The type and duration of action of glucocorticoids must be considered in determining appropriate insulin treatments, with daily-ingested intermediate-acting glucocorticoids such as prednisone requiring careful management to prevent hyperglycemia, as noted in 4.
Management Strategies
Management strategies may include administering intermediate-acting (NPH) insulin concomitantly with intermediate-acting steroids, or using long-acting basal insulin for long-acting glucocorticoids or multidose regimens, as discussed in 1 and 3. Adjustments based on anticipated changes in glucocorticoid dosing and point-of-care glucose test results are critical to prevent hyperglycemia and its associated risks, including infections and cardiovascular events, as emphasized in 2 and 4.
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. 5
From the Research
Main Effect of Glucocorticoids on Carbohydrate Metabolism
The main effect of glucocorticoids (GCs) on carbohydrate metabolism is to induce insulin resistance and hyperglycemia by decreasing glucose utilization and increasing hepatic glucose production 6, 7, 8.
Key Mechanisms
- GCs counteract insulin by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis 7, 8
- GCs may attenuate the incretin effect 7
- GCs can decrease glucose utilization and increase hepatic glucose production 6
- GCs can modulate the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin 8
Effects on Glucose Homeostasis
- GCs promote gluconeogenesis in liver 8
- GCs decrease glucose uptake and utilization in skeletal muscle and white adipose tissue by antagonizing insulin response 8
- GCs regulate glycogen metabolism in liver and skeletal muscle 8
- GCs can lead to hyperglycemia and insulin resistance 6, 7, 8
Clinical Implications
- GCs can exacerbate hyperglycemia in patients with pre-existing diabetes mellitus 6, 9
- GCs can induce insulin resistance and diabetes in previously normal patients, although this is unusual 6
- Metformin may be used to limit the metabolic side effects of GC treatment, including hyperglycemia and insulin resistance 10