Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning

To determine whether elevations of cortisol levels have more pronounced eff ects 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 no rmal men each participated in four studies performed in random order. In al l studies, endogenous cortisol levels were suppressed by metyrapone adminis tration, and caloric intake was exclusively under the form of a constant gl ucose infusion. The daily cortisol elevation was restored by administration of hydrocortisone (or placebo) either at 0500 h or at 1700 h. In each stud y, plasma levels of glucose, insulin, C-peptide, and cortisol were measured at all-min intervals for 32 h. The initial effect of the hydrocortisone-induced cortisol pulse was a short -term inhibition of insulin secretion without concomitant glucose changes a nd was similar in the evening and in the morning. At both times of day, sta rting 4-6 h after hydrocortisone ingestion, glucose levels increased and re mained higher than under placebo for at least 12 h. This delayed hyperglyce mic effect was minimal in the: morning but much more pronounced in the even ing, when it was associated with robust increases in serum insulin and insu lin secretion and with a 30% decrease in insulin clearance. Thus, elevations of evening cortisol levels could contribute to alterations in glucose tolerance, insulin sensitivity, and insulin secretion.