Table 4.

Studies examining sleep restriction and leptin, ghrelin, hunger and cortisol

Study	No. and sex of subjects	Age, mean ± sd (yr)	BMI, mean ± sd (kg/m2)	Design	Comparator condition	Intervention	In-lab conditions	Caloric intake	Blood sampling regime	Effect of intervention on
										Leptin	Ghrelin	Hunger	Cortisol
Intensive sampling ≥24-h duration
Mullington, 2003 (90)	10 M	27.2 (22–37)	26.1 (20–34.5)	Fixed order	3 × 8-h TIB BL	88-h TSD, then 3 × 7-h or 14-h TIB REC	Yes	Standardized meals to maintain body weight, but optional to complete them	90 min over 120 h from 2100 h BL 3 to REC 1	↓ Diurnal amplitude, then ↑ in REC cf BL
Guilleminault, 2003 (92)	8 M	19.6 (18–25)	22.9 ± 2.0	Fixed order for sleep variablesa	2 × 8.5-h TIB REC	7 × 4-h TIB SRa	Partial- day release	Standardized meals at 0800, 1200, 1800 h, glucide rich on blood testing days	5 samples over 24 h on SR 7 and REC 2 (0800, 1200, 1800, 2200, 0215 h)	↓ Peak and rhythm amplitude
Spiegel, 2004 (87)	11 M	22 ± 3.3	23.4 ± 1.7	Fixed order	7 × 12-h TIB REC	6 × 4-h TIB SR	Yes, bed rest for last 60 h of condition	Identical between conditions. Day 1 of testing = ivGTT in morning, then identical CBH-rich meals (30 kcal/kg) at 1400, 1900 h, then on d 2 at 0900, 1400, 1900 h	10–30 min over 24 h during last 24 h of SR and REC	↓ Mean 19%, ↓ rhythm amplitude 20%, ↓ acrophase 26% and earlier (2 h)			⇆ Mean, curve shape changed
Nedeltcheva, 2009 (88 and 74)	5 F, 6 M	39 ± 5	26.5 ± 1.5	Randomized, 2 period, crossover	14 × 8.5-h TIB	14 × 5.5-h TIB SR	Partial, <30 min/d outside. Bed rest 48 h pre/post condition	Ad libitum, but intake identical during bed rest periods	30 min over 24 h before BL and 24 h before INT	⇆	⇆	↑ Calories (snacks)	⇆ AUC, curve shape changed
Pejovic, 2010 (95)	11 F, 10 M	23.5 ± 3.3 (nap), 24.6 ± 2.9 (no nap)	23.2 ± 2.8 (nap), 25.0 ± 2.1 (no nap)	Fixed order ± randomized nap	4 × 8-h TIB	1 × TSD ± 2-h nap in pm after TSD, then 2 × REC nights	Yes	Ad libitum, consistent portion sizes, but free choice from menu	30 min over 24 h on BL 4 and after TSD	↑ Mean. Flattening of diurnal rhythm after TSD. No effect of nap.		⇆ Hunger	⇆
Nedeltcheva, 2010 (107)	3 F, 7 M	41 ± 5	27.4 ± 2	Randomized, 2 period, crossover	14 × 8.5-h TIB	14 × 5.5-h TIB	Yes, bed rest 48 h pre/post condition	Individualized, weight loss diet; 90% of RMR. Same in both conditions	30 min over 24 h before BL and 24 h before INT	⇆	↑	↑ Hunger	⇆
Sampling <24-h duration
Spiegel, 2004 (84)	12 M	22 ± 2.0	23.6 ± 2.0	Randomized, 2 period, crossover	2 × 10-h TIB	2 × 4-h TIB SR	Partial- day release	Standard meals at 1900 and 0800 h, ad libitum at home during d 1. Continuous iv gluc infusion 5 g/kg on d 2	20 min from 0800–2100 h after second night of condition	↓ Mean 18%	↑ 28%	↑ Hunger 24%
Schmid, 2008 (104)	9 M	24.2 ± 3	23.8 ± 1.8	Randomized, 3 period, crossover	1 × 7-h TIB	1 × 4.5-h TIB SR/1 × TSD	Yes	Fasted	Fasting morning sample (0700 and 0730 h, results averaged)	⇆	↑ in TSD	↑ Hunger in TSD
Schmid, 2009 (106)	15 M	27.1 ± 5.0	22.9 ± 1.2	Randomized, 2 period, crossover	2 × 8.25-h TIB	2 × 4.25-h TIB SR	Partial-day release day 1	Standard breakfast, then ad libitum	Hourly from 0800 to 2300 h on d 2 of condition	⇆	⇆	⇆ Hunger, ↓ activity, ⇆ intake
Schmid, 2011 (111) and 2009 (81)	10 M	25.3 ± 4.4	23.8 ± 1.6	Randomized, 2 period, crossover	1 × 7-h TIB	1 × 4.5-h TIB SR	Yes	Fasted on morning of hypoglycemic clamp	30 min during 4 h hypoglycemic clamp			⇆ Basal	↓ Basal, ⇆ peak
Magee, 2009 (103)	10 M	20.4 ± 1.6	Not stated	Fixed order	1 × 8-h TIB BL	2 × 5-h TIB SR, then 1 × 8–10-h TIB REC	Partial-day release, REC night at home	Standardized breakfast and evening meal	Fasting daily morning samples, except SR 1	⇆	⇆	↓ Satiety
van Leeuwen, 2010 (79)	23 M	23.1 ± 2.5	23.2 ± 2.6	Randomized, controlled, parallel group	10 × 8-h TIB (CON n = 8)	2 × 8-h TIB BL, 5 × 4-h TIB SR, 3 × 8-h TIB REC (INT, n = 15)	Yes	Identical daily calories, except 50 kcal/d more in SR	Morning sample (0730 h) on BL 2, SR 5, REC 2	↑		⇆	∼ Peak delayed by 16 min
Simpson, 2010 (89)	67 F, 69 M	30.4	24.7	Randomized, controlled, parallel groupb	2 × 10-h TIB BL	5 × 4-h TIB SR, subset randomized to further 2 × SR (0, 2, 4-h TIB, n = 27) or 2 × REC (6, 8, 10-h TIB, n = 37)	Yes	3 meals plus ad libitum snacks	Fasting morning sample (between 1030 and 1200 h) on BL 2, SR 5, and FSR 2 or REC 2	↑, more in F. With FSR, further ↑ in F and M, and ↓ with REC
Donga, 2010 (78)	5 M, 4 F	44.6 ± 14.7	23.8 ± 2.4	Randomized, 2 period, crossover	1 × 8.5-h TIB	1 × 4-h TIB SR	Yes	Fasted from 2200 h	3-h hyperinsulinemic euglycemic clamp				⇆
Omisade, 2010 (105)	15 F	21.6 ± 2.2	24.5 ± 8.1	Fixed order	1 × 10-h TIB	1 × 3-h TIB SR	Partial, 1 h/d outside	Same intake for each condition	Salivary samples at 0830 and 2000 h	↑ in am, not in pm		⇆	↓ am, ↑ pmc
Bosy-Westphal, 2008 (80)	14 F	27.5 ± 5.3	25.8 ± 5.8	Fixed order	2 × >8-h TIB BL	1 × 7-h, 2 × 6-h, 1 × 4-h TIB SR, then 2 × >8-h TIB REC	No	Ad libitum	With OGTT on BL 2, SR 4 (0, 15, 30, 45, 90 min). Basal levels on REC 2.	↑ Basal level, 45, 90 min; ↑ L/fat mass 29%	⇆	⇆ Hunger, ↑ intake	⇆

M, Male; F, female; BL, baseline; SR, sleep restriction; REC, recovery; FSR, further sleep restriction; CON, control group; INT, intervention; CBH, carbohydrate; AUC, area under curve; ivGTT, iv glucose tolerance test; gluc, glucose; RMR, resting metabolic rate; ⇆, no change; ↑, increased; ↓, decreased.

^aRandomized to early (from 2230 h) or late (from 0215 h) SR.

^bControl group of n = 9 with 10-h TIB throughout. No changes in leptin levels.

^cSeven cortisol samples between 0830 and 2100 h, approximately 10 salivary cortisol samples during the day.