eplerenone and Glucose-Intolerance

Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in patients with heart failure (HF). However, spironolactone, a non-selective MRA, has been shown to exert a harmful effect on glucose homeostasis. The objective of this multicenter, randomized, controlled, double-blind trial was to compare the effects of spironolactone to those of the selective MRA eplerenone on glucose homeostasis among 62 HF patients with glucose intolerance or type II diabetes. Trial registration number:NCT01586442.

Topics: Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Eplerenone; Female; Glucose Intolerance; Glycated Hemoglobin; Heart Failure; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prospective Studies; Spironolactone; Stroke Volume

Topics: Adipose Tissue; Animals; Antihypertensive Agents; Diet, High-Fat; Eplerenone; Glucose Intolerance; Male; Mice; Mice, Inbred C57BL; Obesity; Renin-Angiotensin System; Weight Gain

Although some clinical studies have suggested that spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, appears to increase the blood glucose levels, experimental studies have not supported this notion. Here, we investigated the effect of SPL on blood glucose levels in SHR/NDmcr-cp(cp/cp) (ND) rats, an animal model of metabolic syndrome, in comparison with that of eplerenone (EPL), another MR antagonist. At the same dose of 100 mg/kg, SPL and EPL increased the urinary sodium-to-potassium ratio to a comparable extent, indicating that both agents have similar renal MR antagonistic efficacy in ND rats. Interestingly, SPL but not EPL significantly increased the level of blood glucose. The oral glucose tolerance test revealed that treatment with SPL led to glucose intolerance. The levels of serum insulin and adiponectin, regulators of the blood glucose level, were virtually unaffected by treatment with SPL. On the other hand, SPL induced a marked increase in the blood level of aldosterone, known to be a risk factor for insulin resistance. These results demonstrate that in comparison with EPL, SPL characteristically impairs glucose tolerance in an animal model of metabolic syndrome, in association with a higher blood level of aldosterone.

Topics: Animals; Area Under Curve; Blood Glucose; Eplerenone; Glucose; Glucose Intolerance; Metabolic Syndrome; Mineralocorticoid Receptor Antagonists; Potassium; Rats; Sodium; Spironolactone