Table 2.
Human misalignment studies measuring fasting glucose, insulin, and lipid profiles
| References | Study Design | Gender | Age | BMI, kg/m2 | Misalignment Protocol | Plasma Glucose | Plasma Insulin | Lipid Profile |
|---|---|---|---|---|---|---|---|---|
| Simulated night shift work/Circadian misalignment | ||||||||
| Grant et al. (46) | Control parallel study | 11 (M) | 18–45 | 22–23 | Simulated night work; 1600–1000 Randomly assigned into eating at night (NE) vs. not eating at night (NEN) NE; n = 4 meals; 0700, 1900, 0130 NEN; n = 7 meals; 0700, 0930, 1610, 1900 |
↔ Fasting glucose (NEN vs. NE) Postprandial glucose impaired |
↔ Fasting insulin (NEN vs. NE) Postprandial insulin impaired |
Not measured |
| Morris et al. 2016. (10) | Crossover design | M (3) F (6) |
24–48 | R: 19.3–29.3 | 3 days day 1- sleep/wake cycle inverted by 12 h, followed by staying awake for 16 h Next sleep opportunity- 11:00 AM until 7:00 PM. Sleep/wake protocol maintained until day 3 |
↔ Fasting glucose (aligned vs. misaligned) Postprandial glucose impaired |
↔ Fasting insulin (aligned vs. misaligned) Late phase postprandial insulin 10% higher in circadian misalignment group |
Not measured |
| Morris et al. (47) | Within-participant crossover design | M (8) F (6) |
20–49 | R: 21–29.5 25.4 ± 2.6 |
8-day long protocol: Circadian alignment—participants sleep opportunity occurred between 11:00 PM and 7:00 AM. Circadian misalignment—day 1–3 = 11:00 PM–7:00 AM. day 4—behavioral cycles shifted by 12 h until end of protocol. |
↔ Fasting glucose (aligned vs. misaligned) Postprandial glucose impaired |
↔ Fasting insulin (aligned vs. misaligned) ↔ Fasting ISR (aligned vs. misaligned) ↔ Fasting ISR (AUC) (aligned vs. misaligned) Postprandial insulin impaired |
↑ Fasting FFA levels (misaligned vs. aligned) ↔ FFA (AUC) (misaligned vs. aligned) ↔ TG (AUC) (misaligned vs. aligned) |
| Wefers et al. (48) | Randomized crossover design | M (14) | 22.4 ± 2.8 | 22.3 ± 2.1 | 3-day control protocol and 3.5 day misalignment protocol (12-h rapid shift of cycle). Misalignment participants had matched study procedures to control (e.g., meal time) but 12 h shifted. |
↑ Fasting glucose (misalignment vs. aligned) | ↑ Fasting insulin (misalignment vs. aligned) ↔ Hepatic insulin sensitivity (misalignment vs. aligned) |
↑ Fasting FFA levels (misalignment vs. aligned) ↓ TG (misaligned vs. aligned) ↓ TG (misalignment vs. aligned) |
| Dim light vs. bright light at night | ||||||||
| Albreiki et al. (49) | Randomized two-way crossover study—healthy subjects | M (9) F (8) |
22.3 ± 3.6–22.6 ± 2.2 | 22.9 ± 2.5–22.7 ± 2.2 | Dim light (<5 lux) (DL) vs. bright light (BL) (>500 lux)—between 1800 and 0600 the next day | ↔ Fasting glucose (DL vs. BL) ↑ Postprandial glucose in bright light group |
↔ Fasting insulin (TAUC) (DL vs. BL) | ↑ NEFA in dim light (TAUC) ↔ TAGs (DL vs. BL) |
| Phase advanced/delay misalignment | ||||||||
| Gonnissen et al. (50) | Randomized, single-blinded, crossover design | M (7) F (6) |
24.3 ± 2.5 | 23.6 ± 1.7 | Phase delay: three light-entrained circadian cycles (3 × 21 h—phase advance or 3 × 27 h—phase delay) | Not measured | ↑ Fasting insulin levels (phase delay effect) ↑ HOMA-IR index (phase delay effect) |
Not measured |
| Gonnissen et al. (51) | Randomized single-blinded crossover study | (NS) | 24.3 ± 2.5 | 23.6 ± 1.7 | Three conditions—21, 24, and 27 h cycles. Patients participated in the 24-h control cycle and then 21 and 27 cycle conditions were followed in random order. 24 h—subjects slept for 8 h and awoke for 16 h 21 and 27—subjects stayed time blinded in a respiration chamber during 3 light entrained circadian cycles. |
↔ Fasting glucose (phase advanced) ↑ Fasting glucose (phase delayed) |
↑ Fasting Insulin (phase advanced) ↔ Fasting Insulin (phase delay) |
Not measured |
| Wehrens et al. (44) | NS | 25–45 | 21.5–35.7 | Phase delay for 4 days: Awake for 30.5 h followed by a 4-h recovery nap and a recovery sleep |
↔ Fasting glucose (baseline vs. sleep deprivation) | ↔ Fasting Insulin (baseline vs. sleep deprivation) | ↑ Fasting FFA levels (baseline vs. sleep deprivation) ↓ TG (baseline vs. sleep deprivation) |
|
| Sleep fragmentation | ||||||||
| Stamatakis et al. (52) | M (9) F (2) |
18–29 | 24.3 ± 0.9 | Sleep was experimentally fragmented for 2 nights using auditory and mechanical stimuli | ↓ Glucose effectiveness (post-fragmentation vs. pre-fragmentation) | ↓ Insulin sensitivity (IVGTT) (post-fragmentation vs. pre-fragmentation) | Not measured | |
| Sleep restriction | ||||||||
| Eckel et al. (53) | Crossover counterbalanced design. | F (8) M (8) |
22.4 ± 4.8 | 22.9 ± 2.4 | Restricted sleep schedule: Simulated 5-day work week of 5 h per night sleep |
Not measured | ↓ Insulin sensitivity(OGTT and IVGTT) | Not measured |
| Sleep restriction with different light exposures | ||||||||
| Gil-Lozano et al. (54) | Randomized study design. | M (8) | 21.1 ± 0.9 | 23.9 ± 1 | T1—normal light-dark cycle with regular sleep T2—sleep deprivation in the dark T3—sleep deprivation with nocturnal light exposure T4—sleep deprivation with nocturnal filtered light exposure |
Not measured | ↓ Fasting insulin (5 h postmeal) (regular sleep vs. sleep deprived 6:00 AM) | Not measured |
| Sleep restriction plus phase delay | ||||||||
| Buxton et al Shea. (55) | F (10) M (11) |
23 ± 2 = young 60 ± 5 = older |
(NS) | Spent >5 wk in controlled laboratory conditions. Initial baseline segment of optimal sleep and 3 wk of sleep restriction (5.6 h per 24 h) combined with circadian disruption (recurring 28 h days). | ↔ Fasting glucose (baseline vs. sleep deprivation) ↑ Fasting glucose AUC (baseline vs. sleep deprivation) |
↓ Fasting insulin ↓ Fasting insulin AUC (baseline vs. sleep deprivation) |
Not measured | |
| Sleep restriction plus circadian misalignment vs. sleep restriction | ||||||||
| Leproult et al. (56) | Parallel group design | F (7) M (19) |
Mean—22.5 | Alignment group—23.1 ± 2.4 Misalignment—22.2 ± 2.5 |
Circadian alignment: 3 inpatient days with 10 h bedtimes followed by 8 inpatient days of sleep restriction to 5 h with fixed nocturnal bedtimes Circadian misalignment: sleep delayed by 8.5 h with sleep restriction to 5 h |
↓ Glucose (circadian alignment vs. misalignment) | ↑ Insulin (circadian alignment vs. misalignment) | Not measured |
Values in parentheses in Gender column represent number of subjects. AUC, area under the curve; FFA, free fatty acid; HOMA-IR, homeostatic model assessment for insulin resistance; ISR, insulin secretion rate; IVGTT, intravenous glucose tolerance test; NEFA, nonesterified fatty acids; OGTT, oral glucose tolerance test; TAG, triacylglycerol; TAUC, time area under curve; TG, triglycerides.