Peter Y Liu1,2, Darian Lawrence-Sidebottom3,4, Katarzyna Piotrowska1, Wenyi Zhang1, Ali Iranmanesh5, Richard J Auchus6,7, Johannes D Veldhuis8, Hans P A Van Dongen3,9. 1. Division of Endocrinology, The Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, USA. 2. David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. 3. Sleep and Performance Research Center, Washington State University, Spokane, WA, USA. 4. Neuroscience Graduate Program, Washington State University, Pullman, WA, USA. 5. Endocrinology Service, VA Medical Center, Salem, VA, USA. 6. Division of Metabolism, Diabetes, and Endocrinology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 7. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA. 8. Endocrine Research Unit, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, MN, USA. 9. Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA.
Abstract
CONTEXT: Sleep loss in men increases cortisol and decreases testosterone, and sleep restriction by 3 to 4 hours/night induces insulin resistance. OBJECTIVE: We clamped cortisol and testosterone and determined the effect on insulin resistance. METHODS: This was a randomized double-blind, in-laboratory crossover study in which 34 healthy young men underwent 4 nights of sleep restriction of 4 hours/night under 2 treatment conditions in random order: dual hormone clamp (cortisol and testosterone fixed), or matching placebo (cortisol and testosterone not fixed). Fasting blood samples, and an additional 23 samples for a 3-hour oral glucose tolerance test (OGTT), were collected before and after sleep restriction 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: Sleep restriction 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 sleep restriction alone. CONCLUSION: Fixing cortisol-testosterone exposure mitigates the development of insulin resistance and hyperinsulinemia, but not hyperglycemia, from sustained sleep restriction in men. The interplay between cortisol and testosterone may be important as a mechanism by which sleep restriction impairs metabolic health.
CONTEXT: Sleep loss in men increases cortisol and decreases testosterone, and sleep restriction by 3 to 4 hours/night induces insulin resistance. OBJECTIVE: We clamped cortisol and testosterone and determined the effect on insulin resistance. METHODS: This was a randomized double-blind, in-laboratory crossover study in which 34 healthy young men underwent 4 nights of sleep restriction of 4 hours/night under 2 treatment conditions in random order: dual hormone clamp (cortisol and testosterone fixed), or matching placebo (cortisol and testosterone not fixed). Fasting blood samples, and an additional 23 samples for a 3-hour oral glucose tolerance test (OGTT), were collected before and after sleep restriction 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: Sleep restriction 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 sleep restriction alone. CONCLUSION: Fixing cortisol-testosterone exposure mitigates the development of insulin resistance and hyperinsulinemia, but not hyperglycemia, from sustained sleep restriction in men. The interplay between cortisol and testosterone may be important as a mechanism by which sleep restriction impairs metabolic health.
Authors: Anita M van den Hoek; Annemieke C Heijboer; Eleonora P M Corssmit; Peter J Voshol; Johannes A Romijn; Louis M Havekes; Hanno Pijl Journal: Diabetes Date: 2004-08 Impact factor: 9.461
Authors: B M K Biller; A B Grossman; P M Stewart; S Melmed; X Bertagna; J Bertherat; M Buchfelder; A Colao; A R Hermus; L J Hofland; A Klibanski; A Lacroix; J R Lindsay; J Newell-Price; L K Nieman; S Petersenn; N Sonino; G K Stalla; B Swearingen; M L Vance; J A H Wass; M Boscaro Journal: J Clin Endocrinol Metab Date: 2008-04-15 Impact factor: 5.958