Sleep duration and regularity → Insulin resistance (HOMA-IR)

Mechanism

Spiegel, Leproult, and Van Cauter restricted sleep in eleven young men. Intravenous glucose tolerance fell toward a pre-diabetic band. That is the identifying trial. Nedeltcheva and colleagues kept eleven adults on 5.5-hour nights for two weeks of sitting and free eating. Two-hour oral glucose rose and insulin sensitivity fell, with the same weight gain as on 8.5-hour weeks. Buxton and colleagues kept twenty men on 5-hour nights for a week. Insulin sensitivity fell about 20 percent on an intravenous glucose test and about 11 percent on a clamp. Modafinil, which they randomized, did not prevent the drop. Broussard and colleagues biopsied fat cells after four 4.5-hour nights in seven adults. Insulin had a harder time turning on Akt, and whole-body insulin sensitivity fell. Rao and colleagues used a clamp after five 4-hour nights in fourteen people. Peripheral insulin sensitivity fell about 29 percent. Liver glucose production did not. Zuraikat and colleagues cut sleep by about 90 minutes for six weeks in thirty-eight women. Fasting insulin and HOMA-IR rose, not through fat mass. The rise was larger after menopause. Singh and colleagues ran four short nights in postmenopausal women, then a clamp. Nine of fourteen were analyzed. The glucose infusion rate fell. Diet changes the picture. On a reducing diet, Nedeltcheva 2012 saw no loss of oral glucose control in ten overweight adults; 24-hour insulin went down. Cros and colleagues overfed ten people for six days. The overfeed raised liver fat and endogenous glucose production. Adding 4-hour nights did not move those numbers further. Buxton 2012 mixed three weeks of 5.6-hour sleep with 28-hour days in twenty-one adults. After a meal, glucose ran higher because the pancreas put out too little insulin. Nine recovery days put both back. Ness and colleagues found two 10-hour nights after five short nights in fifteen men restored the fat-release pattern, not the insulin-sensitivity drop.

Caveats

The early trials are small and inpatient. Spiegel is eleven men. Broussard is seven. Singh analyzed nine. Zuraikat is the largest randomized sample here, thirty-eight women, and it is still six weeks of restriction, not a decade of short sleep. A calorie deficit can hide the glucose hit. Nedeltcheva 2012 saw no loss of glucose control when the same restriction sat on a reducing diet. Cros 2019 saw no extra glucose hit when restriction sat on a six-day overfeed. Those are context, not a failed replication of restriction alone. Two weekend nights did not restore insulin sensitivity in Ness 2020. Nine days of recovery plus a stable clock did in Buxton 2012, but that protocol also shifted the day length. Shift work is a mixed exposure. Ness and Buxton 2012 used sequential laboratory schedules, not a coin-flip between sleep lengths. The stamp stays robust causal because Spiegel's design already set it. Eleven papers do not make the stamp more certain.

Effect

qualitative. Spiegel 1999 (N=11): sleep debt impaired IVGTT glucose tolerance. Later RCTs: clamp, HOMA-IR, adipocyte signaling. Restriction on a reducing diet did not worsen glucose (Nedeltcheva 2012).

Nodes

Named confounders

• Alcohol intake
• Ultra-processed food intake

Papers

• Impact of sleep debt on metabolic and endocrine function

  K. Spiegel, R. Leproult, E. Van Cauter · 1999 · The Lancet

• Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance.

  AV Nedeltcheva, L Kessler, J Imperial, PD Penev · 2009 · The Journal of clinical endocrinology and metabolism

• Sleep restriction for 1 week reduces insulin sensitivity in healthy men.

  OM Buxton, M Pavlova, EW Reid, W Wang, DC Simonson, GK Adler · 2010 · Diabetes

• Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss.

  AV Nedeltcheva, JG Imperial, PD Penev · 2012 · Obesity (Silver Spring, Md.)

• Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.

  JL Broussard, DA Ehrmann, E Van Cauter, E Tasali, MJ Brady · 2013 · Annals of internal medicine

• Subchronic sleep restriction causes tissue-specific insulin resistance.

  MN Rao, TC Neylan, C Grunfeld, K Mulligan, M Schambelan, JM Schwarz · 2015 · The Journal of clinical endocrinology and metabolism

• Impact of sleep restriction on metabolic outcomes induced by overfeeding: a randomized controlled trial in healthy individuals.

  J Cros, E Pianezzi, R Rosset, L Egli, P Schneiter, F Cornette, B Pouymayou, R Heinzer · 2019 · The American journal of clinical nutrition

• Effect of sleep restriction on insulin sensitivity and energy metabolism in postmenopausal women: A randomized crossover trial.

  P Singh, RA Beyl, JM Stephens, RC Noland, AJ Richard, A Boudreau, RC Hebert, E Ravussin · 2023 · Obesity (Silver Spring, Md.)

• Chronic Insufficient Sleep in Women Impairs Insulin Sensitivity Independent of Adiposity Changes: Results of a Randomized Trial.

  FM Zuraikat, B Laferrère, B Cheng, SE Scaccia, Z Cui, B Aggarwal, S Jelic, MP St-Onge · 2023 · Diabetes care

• Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption.

  OM Buxton, SW Cain, SP O'Connor, JH Porter, JF Duffy, W Wang, CA Czeisler, SA Shea · 2012 · Science translational medicine

• Two nights of recovery sleep restores the dynamic lipemic response, but not the reduction of insulin sensitivity, induced by five nights of sleep restriction.

  KM Ness, SM Strayer, NG Nahmod, AM Chang, OM Buxton, GC Shearer · 2020 · American journal of physiology. Regulatory, integrative and comparative physiology