Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men

Abstract

Context Sleep loss in men increases cortisol and decreases testosterone, and sleep restriction by 3–4 h/night induces insulin resistance. Objective We clamped cortisol and testosterone and determined the effect on insulin resistance. Design and Setting Randomized double-blind, in-laboratory crossover study. Participants 34 healthy young men. Intervention 4 nights of sleep restriction (SR) of 4 hours/night under two treatment conditions in random order: dual hormone clamp (cortisol and testosterone fixed), or matching placebo (cortisol and testosterone not fixed). Main Outcome Measures Fasting blood samples, and an additional 23 samples for a 3-hour oral glucose tolerance test (OGTT), were collected before and after SR under both treatment conditions. Cytokines and hormones were measured from the fasting samples. Overall insulin sensitivity was determined from the OGTT by combining complementary measures: homeostasis model assessment of insulin resistance of the fasting state; Matsuda Index of the absorptive state, and; minimal model of both fasting and absorptive states. Results SR alone induced hyperinsulinemia, hyperglycemia and overall insulin resistance (P<0.001 for each). Clamping cortisol and testosterone alleviated the development of overall insulin resistance (p=0.046) and hyperinsulinemia (p=0.014) by 50%. Interleukin-6, high sensitivity C-reactive protein, peptide YY, and ghrelin did not change, whereas tumor necrosis factor-α and leptin changed in directions that would have mitigated insulin resistance with SR alone. Conclusions Fixing cortisol-testosterone exposure mitigates the development of insulin resistance and hyperinsulinemia, but not hyperglycemia, from sustained SR in men. The interplay between cortisol and testosterone may be important as a mechanism by which SR impairs metabolic health.

Associations of testosterone and cortisol concentrations with sleep quality in Japanese male workers

“…During slow wave sleep, sympathetic nervous activity is decreased and cortisol secretion is inhibited [ 33 ]. Sleep loss prevents the usual fall in cortisol concentrations that occur during the late afternoon and early evening [ 34 ]. HPA axis activation is a primary stress-mediating pathway leading to increased peripheral cortisol concentrations [ 35 ].…”

The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story

“…Cortisol plays a critical role in the wakening response in the early morning and in glucose homeostasis. Circadian disruption disturbs the daily rhythm of cortisol secretion and induces hypercortisolemia, which leads to hepatic and peripheral insulin resistance [ 91 ].…”

Sleep, testosterone and cortisol balance, and ageing men

“…Administration of glucocorticoids to bolster cortisol levels in the late afternoon and early evening also induces insulin resistance [ 69 , 73 , 74 ] through post-receptor mechanisms [ 90 – 92 ]. Nevertheless, direct substantiation of the role of testosterone-cortisol balance in the induction of insulin resistance from sleep restriction has only recently become available in a study that utilized a novel dual hormonal clamp [ 93 ].…”

“…Thirty-four healthy young mostly overweight men completed a randomized two-condition crossover study in a highly controlled in-laboratory environment [ 93 ]. Under both conditions, participants underwent one night of 10 h baseline sleep (2200–0800) followed by 4 consecutive nights where sleep was restricted to a 4 h opportunity (0100–0500).…”

“…In the placebo condition (where matching placebos for ketoconazole, hydrocortisone and testosterone were administered), cortisol and testosterone were not clamped. Fixing testosterone-cortisol balance mitigated the development of insulin resistance and hyperinsulinemia with 4 consecutive nights of sleep restriction by at least 50%, but did not prevent the development of hyperglycemia [ 93 ]. Future studies will be required to determine the relative contribution of testosterone and cortisol in inducing these metabolic changes, by individually clamping each hormone.…”