Low-dose dexamethasone administration for 3 weeks favorably affects plasma HDL concentration and composition but does not affect very low-density lipoprotein kinetics

Abstract

Objective: Subclinical hypercortisolemia often occurs in subjects with features of the metabolic syndrome, and it has been suggested that it may be, at least in part, responsible for the development of these metabolic abnormalities. However, the metabolic effects of glucocorticoid administration to mimic subclinical glucocorticoid excess have not been evaluated.

Methods: We used stable isotope-labeled tracer methods in conjunction with magnetic resonance techniques to measure the effect of glucocorticoid excess within the physiological range (~0.7 mg dexamethasone/day for 3 weeks) on glucose and free fatty acid (FFA) rates of appearance (Ra) into plasma, intrahepatic triglyceride (TG) content, very low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics and plasma lipoprotein subclass concentrations, and particle sizes in nine overweight and obese individuals.

Results: Dexamethasone treatment led to a very small but significant increase in body weight (from 87.4±7.1 to 88.6±7.2 kg; P=0.003) and increased HDL-cholesterol (from 45.9±2.8 to 55.1±4.6 mg/dl; P=0.037) and HDL particle (from 33.7±2.2 to 41.4±4.2 nmol/l; P=0.023) concentrations in plasma but had no effect on intrahepatic TG content, glucose and FFA Ra in plasma, hepatic VLDL-TG and VLDL-apoB-100 secretion rates and mean residence times in the circulation, plasma TG and LDL-cholesterol concentrations, and plasma lipoprotein particle sizes.

Conclusion: Subclinical hypercortisolemia does not have significant adverse metabolic consequences.

Conflict of interest statement

DECLARATION OF INTEREST

The authors have no conflicts of interest relevant to the content of this article.

Figures

Figure 1

Glucose and free fatty acid (FFA) rates of appearance (Ra) in plasma and hepatic (HISI) and adipose tissue (ATISI) insulin sensitivity index before and after dexamethasone treatment. Data are mean ± SEM (glucose and FFA Ra) or medians with quartiles (HISI and ATISI). There was a trend for a decrease in HISI and ATISI but it did not reach statistical significance at the P ≤ 0.05 level (P = 0.066 and 0.086, respectively).

Figure 2

Very low-density lipoprotein (VLDL) triglyceride (TG) and VLDL apolipoprotein B-100 (apoB-100) secretion rates and mean residence times (MRT) in plasma before and after dexamethasone treatment. Data are mean ± SEM.