From the Guidelines
Glucocorticoids have a profound impact on lipid metabolism, leading to increased levels of total cholesterol, VLDL, and triglycerides, as well as changes in LDL particle size and density, primarily due to their effects on weight gain, insulin resistance, and lipid metabolism. The most recent and highest quality study, 1, published in 2016 in the European Heart Journal, highlights the adverse effects of glucocorticoid therapy on lipid metabolism. According to this study, glucocorticoids cause weight gain and exacerbate insulin resistance, resulting in increased levels of total cholesterol, VLDL, and triglycerides, as well as changes in LDL particle size and density.
Key Effects of Glucocorticoids on Lipid Metabolism
- Increase in total cholesterol, VLDL, and triglycerides
- Changes in LDL particle size and density
- Weight gain and insulin resistance
- Increased activity of hepatic lipase and decreased activity of lipoprotein lipase
The effects of glucocorticoids on lipid metabolism are dose-dependent and typically more pronounced with long-term therapy. As noted in 1, a study published in 2010 in the Annals of the Rheumatic Diseases, the use of low-dose corticosteroids may not significantly contribute to enhanced cardiovascular risk, whereas high-dose corticosteroids may have a more pronounced effect. Therefore, it is essential to monitor lipid profiles regularly in patients on chronic glucocorticoid therapy and consider lipid-lowering medications if significant dyslipidemia develops.
From the Research
Effects of Glucocorticoids on Lipid Metabolism
- Glucocorticoids (GCs) have been shown to increase total cholesterol and low-density lipoprotein cholesterol levels 2
- High-density lipoprotein cholesterol levels are also increased by GC treatment, with levels gradually increasing over time 2
- Triglyceride levels do not appear to change significantly with GC treatment 2
- GCs increase the amount of fatty acids in circulation, which can lead to ectopic fat distribution, including in the liver, muscle, and central adipocytes 3
- Glucocorticoids promote preadipocyte conversion to mature adipocytes, causing hyperplasia of the adipose tissue, and have acute antilipolytic effects on adipocytes 3
Mechanisms of Glucocorticoid-Induced Changes in Lipid Metabolism
- GCs stimulate de novo lipogenesis in hepatocytes, leading to increased lipid production in the liver 3, 4
- GCs increase the release of free fatty acids from adipose stores and stimulate their uptake by the liver, contributing to lipid deposition 4
- GCs also inhibit β-oxidation of fatty acids, further contributing to lipid accumulation in the liver 4
- The effects of GCs on lipid metabolism are complex and may involve multiple mechanisms, including changes in appetite, glucose and insulin homeostasis, and lipid catabolism 3, 4, 5
Clinical Implications of Glucocorticoid-Induced Changes in Lipid Metabolism
- GC treatment can lead to dyslipidemia, characterized by elevations in total plasma cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol 6
- GC-induced dyslipidemia and hypertension may predispose patients to coronary artery disease, particularly with high-dose and prolonged GC treatment 6