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

Abstract

CONTEXT\nSleep loss in men increases cortisol and decreases testosterone, and sleep restriction by 3-4 h/night induces insulin resistance.\n\n\nOBJECTIVE\nWe clamped cortisol and testosterone and determined the effect on insulin resistance.\n\n\nDESIGN AND SETTING\nRandomized double-blind, in-laboratory crossover study.\n\n\nPARTICIPANTS\n34 healthy young men.\n\n\nINTERVENTION\n4 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).\n\n\nMAIN OUTCOME MEASURES\nFasting 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.\n\n\nRESULTS\nSR 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.\n\n\nCONCLUSIONS\nFixing 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.