Glucose ingestion selectively amplifies ACTH and cortisol secretory-burst mass and enhances their joint synchrony in healthy men.

CONTEXT

Glucose intake is associated with a variable increase in adrenal glucocorticoid secretion.

HYPOTHESIS

Glucose ingestion elevates cortisol secretion by 1) augmenting pulsatile ACTH release; and/or 2) enhancing ACTH-cortisol synchrony or dose-responsiveness.

SUBJECTS

Fifty-eight healthy men ages 19-78 yr with computed tomography-estimated abdominal visceral fat participated in the study.

LOCATION

The study was conducted at the Clinical Translational-Research Center and Veterans Affairs Medical Center.

METHODS

We conducted frequent sampling of plasma ACTH and cortisol concentrations after glucose vs. water ingestion in the fasting state, as well as deconvolution, approximate entropy, linear-regression, and dose-response analysis.

OUTCOMES

After water ingestion, age was a negative correlate of the mass of ACTH (P = 0.009; R(2) = 0.119) and of cortisol (P < 0.001; R(2) = 0.269) secreted per burst. Glucose ingestion abolished both relationships but amplified pulsatile ACTH (P = 0.009) and cortisol (P = 0.001) secretion. Glucose exposure selectively augmented the mass of ACTH (P < 0.001) and of cortisol (P = 0.004) secreted per burst without altering burst number or basal secretion. The increment in pulsatile ACTH strongly predicted the increment in pulsatile cortisol (P < 10(-4); R(2) = 0.325) secretion. Abdominal visceral fat positively forecast the glucose-induced increment in cortisol secretory-burst mass (P = 0.019). According to approximate entropy analysis, glucose input also enhanced the joint synchrony of ACTH-cortisol secretory patterns (P ≤ 0.001). Caloric intake did not affect analytical dose-response estimates of ACTH potency and efficacy or adrenal sensitivity.

CONCLUSION

Conjoint augmentation of the mass of ACTH and cortisol secreted per burst and enhancement of ACTH-cortisol synchrony underlie glucose-induced glucocorticoid secretion in healthy men. Visceral adiposity is a predictor of the glucose-stimulated increment in burst-like cortisol output, suggesting an additional possible mechanism for increased cardiovascular risk in abdominal obesity.