Metabolic Effects of Short-Term Elevations of Plasma Cortisol Are More Pronounced in the Evening Than in the Morning 1

Abstract

To determine whether elevations of cortisol levels have more pro- nounced effects on glucose levels and insulin secretion in the evening (at the trough of the daily rhythm) or in the morning (at the peak of the rhythm), nine normal men each participated in four studies per- formed in random order. In all studies, endogenous cortisol levels were suppressed by metyrapone administration, and caloric intake was exclusively under the form of a constant glucose infusion. The daily cortisol elevation was restored by administration of hydrocor- tisone (or placebo) either at 0500 h or at 1700 h. In each study, plasma levels of glucose, insulin, C-peptide, and cortisol were measured at 20-min intervals for 32 h. The initial effect of the hydrocortisone-induced cortisol pulse was a short-term inhibition of insulin secretion without concomitant glu- cose changes and was similar in the evening and in the morning. At both times of day, starting 4–6 h after hydrocortisone ingestion, glucose levels increased and remained higher than under placebo for at least 12 h. This delayed hyperglycemic effect was minimal in the morning but much more pronounced in the evening, when it was associated with robust increases in serum insulin and insulin secre- tion and with a 30% decrease in insulin clearance. Thus, elevations of evening cortisol levels could contribute to al- terations in glucose tolerance, insulin sensitivity, and insulin secretion.