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Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans
Open accessAbstract
Leptin and adiponectin play important physiological roles in regulating appetite, food intake, and energy balance and have pathophysiological roles in obesity and anorexia nervosa. To assess the relative contributions of day/night patterns in behaviors (sleep/wake cycle and food intake) and of the endogenous circadian pacemaker on observed day/night patterns of adipokines, in six healthy subjects we measured circulating leptin, soluble leptin receptor, adiponectin, glucose, and insulin levels throughout a constant routine protocol (38 h of wakefulness with constant posture, temperature, and dim light, as well as identical snacks every 2 h) and throughout sleep and fasting periods before and after the constant routine. There were significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening. Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin. Thus, the day/night pattern in leptin is likely caused by combined effects from the endogenous circadian pacemaker and day/night patterns in behaviors. Our data imply that alterations in the sleep/wake schedule would lead to an increased daily range in circulating leptin, with lowest leptin upon awakening, which, by influencing food intake and energy balance, could be implicated in the increased prevalence of obesity in the shift work population.
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TL;DR
In six healthy subjects, a 38-h constant routine separated endogenous circadian effects from sleep/wake and fasting/feeding effects on adipokines and glucose. Leptin, glucose, and insulin had significant endogenous circadian rhythms peaking near usual awakening, while sleep/fasting and wakefulness/meals produced independent changes in leptin, glucose, and insulin.
Key findings
- Significant group mean circadian rhythms were found for leptin (peak-to-trough 16% of mesor; individual amplitudes averaged 1.4 ng/ml, 21% around a leptin mesor of 6.5 ng/ml; 4/6 subjects significant), insulin (22%, P = 0.02), and glucose (10%, P = 0.001), with peaks around the usual time of awakening. No group mean circadian rhythm was detected for soluble leptin receptor (sOB-R) or adiponectin.
- Independent of circadian effects, all six subjects had a significant linear increase in leptin during prolonged wakefulness/meals: average +3.33 ng/ml over 16 h, a 51% fluctuation around the leptin mesor of 6.5 ng/ml. sOB-R decreased by 3.2 ng/ml per 16 h (19% around mesor 16.3 ng/ml), and adiponectin showed a small significant group decline of 0.18 g/ml over 16 h (4% around mesor 4.05 g/ml), though only one subject had a significant individual decline.
- Independent of circadian effects, each subject had a significant decrease in leptin across sleep/fasting: mean −0.6 ng/ml per hour (range −0.34 to −1.10), equivalent to −4.8 ng/ml over 8 h, a 74% fluctuation around the leptin mesor of 6.5 ng/ml. Sleep/fasting also decreased insulin by −0.45 IU/ml per hour (−3.6 IU/ml over 8 h; 36% around mesor 10.1 IU/ml) and glucose by −0.65 mg/dl per hour (−5.2 mg/dl over 8 h; 5% around mesor 103.4 mg/dl), with no independent sleep-related changes in sOB-R or adiponectin.
- The authors conclude that the day/night leptin pattern reflects combined endogenous circadian and behavioral effects, and that altered sleep/wake schedules could increase the daily range in circulating leptin, with lowest leptin upon awakening, potentially relevant to shift-work-related obesity.
Methods
- Six healthy subjects were studied with a 38-h constant routine protocol: continuous wakefulness, constant semirecumbent posture, constant temperature (~23 ± 2 C), dim light (<8 lux), and identical snacks every 2 h. Sleep and fasting periods were also measured before and after the constant routine, each with 10-h sleep opportunities.
- Hourly blood samples were assayed for leptin, sOB-R, adiponectin, glucose, and insulin; core body temperature was recorded rectally as a circadian phase marker, and sleep was scored from EEG, EOG, and submental EMG.
- Circadian phase and amplitude were estimated by cosinor analysis relative to the core body temperature minimum (CBTmin); group circadian effects were assessed after subtracting individual linear trends, and behavioral effects were assessed after subtracting individual circadian rhythms, using linear regression aligned to the sleep/wake schedule. The average circadian period was 24.6 h (SEM = 0.2 h).
Limitations
- The paper states that separating circadian and behavioral effects relies on the assumption that these effects are additive; this needs direct testing, such as a forced desynchrony study.
- The paper states that it could not independently assess meals from wakefulness, or fasting from sleep, though it argues fasting and meals likely have greater effects than sleep and wakefulness.
- The paper notes that its findings differ from sleep-restriction studies, raising the possibility that incremental sleep restriction differs from acute sleep deprivation, and calls for longer experiments. Evident from the text: the sample was small (six subjects), and the analysis of sleep periods before and after the constant routine relied on extrapolating the circadian component from constant-routine data.
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35 Own result · 20 Not checked yet · 17 Own interpretation · 8 Own method · 2 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were significant mean group circadian variations in both glucose and insulin (Fig. 2, lower left).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There were no independent sleep-related changes in sOB-R or adiponectin, but there were independent sleeprelated decreases in both glucose and insulin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As leptin was increasing, prolonged wakefulness was associated with a significant group mean decrease in sOB-R equivalent to 3.2 ng/ml per 16 h of continuous wakefulness (i.e.19% variability around the sOB-R mesor of 16.3 ng/ml).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“Results in our overweight, but nonobese, subjects in the current study (average BMI, 25 kg/m 2 ) indicated a lack of a significant circadian rhythm of adiponectin.”
- Also stated in: § Discussion · plain
“In contrast, there was no detectable circadian rhythm in either circulating sOB-R or adiponectin levels (right panels).”
- Also stated in: § Discussion · plain
“but no circadian rhythms in sOB-R or adiponectin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
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- Also stated in: § Discussion · plain
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In the paper
“Four of the six subjects had a significant circadian rhythm in circulating leptin (P Ͻ 0.05).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plaincorrelationaln = 4 ·- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no independent sleep-related changes in sOB-R or adiponectin, but there were independent sleeprelated decreases in both glucose and insulin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The average increase was equivalent to 3.33 ng/ml over the usual period of 16 h of continuous wakefulness.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening.”
- Also stated in: § Discussion · plain
“We found significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening, but no circadian rhythms in sOB-R or adiponectin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to the increased circulating leptin during wakefulness, each subject had a significant decrease in leptin across each sleep period (when subjects were also fasting), both before the constant routine and during recovery sleep.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The average circadian period for the subjects in this study was 24.6 h (sem ϭ 0.2 h).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Analysis of circadian rhythmicity and behavioral influences on glucose and hormones
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin.”
- Also stated in: § Effect of wakefulness/meals (independent from circadian effects) · plain
“Independent of any circadian rhythm influences, all six subjects had a significant linear increase in leptin throughout the constant routine (i.e. during prolonged wakefulness with regular food intake).”
- Also stated in: § Discussion · plain
“Importantly, we found that, after subtracting the circadian effect, sleep/fasting was associated with a monotonic decline in leptin, and wakefulness/eating was associated with a monotonic increase in leptin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Effect of wakefulness/meals (independent from circadian effects) · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin.”
- Also stated in: § Effect of sleep/fasting (independent from circadian effects) · plain
“There were no independent sleep-related changes in sOB-R or adiponectin, but there were independent sleeprelated decreases in both glucose and insulin.”
- Also stated in: § Discussion · plain
“In addition, we detected systematic decreases in leptin, glucose, and insulin attributable to the effects of sleep/fasting, and a systematic increase in leptin attributable to wakefulness/food intake.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Effect of sleep/fasting (independent from circadian effects) · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Independent of any circadian rhythm influences, all six subjects had a significant linear increase in leptin throughout the constant routine (i.e. during prolonged wakefulness with regular food intake).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, there were no statistically significant changes in group mean glucose or insulin attributable to prolonged wakefulness/meals.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plainn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“The peak-to-trough amplitudes of the fundamental circadian rhythms averaged 1.4 ng/ml, equivalent to a daily fluctuation of 21% around the leptin mesor of 6.5 ng/ml.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plainn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“There was a very small, but significant, decline in group mean adiponectin during wakefulness equivalent to 0.18 g/ml over the usual period of 16 h of continuous wakefulness (i.e.4% decrease around the adiponectin mesor of 4.05 g/ml).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaindirectn = 6 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“This represents an independent behaviorrelated daytime fluctuation of 51% around the leptin mesor of 6.5 ng/ml (Fig. 3).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, the rate of fall during sleep/fasting was much greater than the rate of increase during wakefulness/eating (mean, ϩ0.21 mg/ml per hour, see above).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean decrease was Ϫ0.6 ng/ml per hour of sleep/ fasting (range, Ϫ0.34 to Ϫ1.10 ng/ml per hour).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, there was no detectable circadian rhythm in either circulating sOB-R or adiponectin levels (right panels).”
- Also stated in: § Discussion · plain
“but no circadian rhythms in sOB-R or adiponectin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, we found significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening, but no circadian rhythms in sOB-R or adiponectin.”
- Also stated in: § Discussion · plain
“There were significant circadian rhythms in circulating leptin, glucose, and insulin (left panels).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, we detected systematic decreases in leptin, glucose, and insulin attributable to the effects of sleep/fasting, and a systematic increase in leptin attributable to wakefulness/food intake.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, we detected systematic decreases in leptin, glucose, and insulin attributable to the effects of sleep/fasting, and a systematic increase in leptin attributable to wakefulness/food intake.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the independent circadian profile is considerably different (i.e.ϳ8 h phase delayed) from the regular day/night leptin profiles when behaviors and meals are uncontrolled (see Discussion).”
- Also stated in: § Discussion · plain
“the endogenous circadian profile of circulating leptin is considerably different (i.e.approximately 8 h phase delayed) from that seen in the previously published, not fully controlled studies.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
In the paper
“Use of continuous enteral administration and shifting of the sleep schedule by 8 h reveals possible independent circadian rhythm and sleep effects on circulating leptin (36).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [36]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, there appears to be a circadian correlation between insulin and leptin (at least for the times of peak insulin and leptin) (Fig. 2), consistent with the previously detected correlation in longer studies of chronic diurnal fasting (40).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [40]
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which, by influencing food intake and energy balance, could be implicated in the increased prevalence of obesity in the shift work population.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
hedgedconditionaln = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“Shifting the time of both sleep and meals by 12 h also shifted the pattern of circulating leptin by the same period (35), but circadian rhythms may have also been changing during the protocol independent from food intake because there was no control of behaviors or light exposure during the wakefulness episodes.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [35]
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fluctuation in sOB-R was opposite to the fluctuation in total leptin, implying that the biologically active free leptin had an even larger increase attributable to the prolonged wakefulness/eating period.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the day/night pattern in leptin is likely caused by combined effects from the endogenous circadian pacemaker and day/night patterns in behaviors.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
hedgedconditionaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The similar rate of decline despite altered sleep suggests that fasting rather than sleep per se causes the linear decrease in circulating leptin.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Almost all previous studies quantifying the day/night pattern in adipokine, glucose, or insulin concentrations allowed sleep/fasting to occur at night and wakefulness/food intake during the day, making it impossible to determine whether the changes seen across the day and night could be due to the pattern of food intake over the 24-h period or the endogenous circadian system.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, a similar study in obese subjects (average BMI, 57.5 kg/m 2 ) failed to demonstrate a similar day/night variation, suggesting that important differences exist between lean vs. obese subjects (41).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [41]
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that important differences exist between lean vs. obese subjects (41).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [41]
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This profile is similar to published 24-h leptin profiles in protocols that permit sleep at night.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Our findings are quite different from other recent research showing that experimentally restricted sleep (4 h per night for 6 nights) lowered both glucose tolerance (51) and the 24-h profile of leptin (52), raising the possibility that incremental sleep restriction may have different effects from acute sleep deprivation.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [51]
- Not checked yetcites [52]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Our data imply that alterations in the sleep/wake schedule can lead to an increased peak-to-trough daily swing in the physiologically active circulating free leptin, which may influence food intake and energy balance and could thus be implicated in the increased obesity and cardiovascular disease in the shift work population (15).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [15]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
None of the sources cited for this claim have been checked yet.
In the paper
“We have recently shown that either shortterm induced hypoleptinemia due to fasting, or long-term hypoleptinemia in conditions in which caloric expenditure exceeds caloric intake, is associated with dysregulation of the central mechanisms regulating neuroendocrine function and energy homeostasis (4, 43).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [4]
- Not checked yetcites [43]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“We recently reported that circulating adiponectin concentrations in healthy lean men (average BMI, 22.8 kg/m 2 ) exhibited a day/night variation, with a significant decline at night, reaching a minimum in the early morning (13).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [13]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This would result in a fluctuation in circulating leptin of more than double the normal 24-h fluctuation.”
- Also stated in: § Discussion · plain
“When sleep occurs at an unusual phase of the body clock (right panel), the circadian and behavioral fluctuations are in phase, and the resultant circulating leptin has a larger 24-h fluctuation.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
- Also stated in: § Discussion · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We were also unable to assess independent effects of meals from wakefulness, or independent effects of fasting from sleep, but overwhelming evidence from this study and other studies suggests that fasting and meals have greater effects when compared with sleep and wakefulness effects.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further studies are needed to assess whether the 24-h leptin profile in response to three meals/d would be different; but, because the circadian peak in leptin coincides with the usual time of awakening in the absence of shift work (left panel of Fig. 4), altering the sleep schedule in either direction and by any amount is expected to always cause a lower trough level of leptin and hypoleptinemia”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the daily leptin profile is likely to change quite considerably when altering the sleep/wake schedule relative to the circadian timing.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“More specifically, summing the three factors that influence circulating leptin tested in the current study (i.e. the circadian system, wakefulness/meals, and sleep/fasting), we have estimated how the usual day/night pattern of circulating leptin is likely to be altered by adjustments in the sleep/wake schedule (Fig. 4).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
- It may state two separate claims as one. 24
- Probably not a substantial claim. 17
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that sleep/fasting causes significant systematic reductions in both glucose and insulin, which is consistent with data from the second half of the sleep periods in these earlier studies.”
- Also stated in: § Discussion · plain
“In addition, we detected systematic decreases in leptin, glucose, and insulin attributable to the effects of sleep/fasting, and a systematic increase in leptin attributable to wakefulness/food intake.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean reduction in circulating glucose was Ϫ0.65 mg/dl per hour, equivalent to Ϫ5.2 mg/dl over the usual sleep period of 8 h (reduction in glucose of 5% around the mesor of 103.4 mg/dl).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both the insulin and glucose levels were highest in the morning, with a substantial peak in the circadian component of insulin around the time of usual awakening (although all of these measurements were made during continued wakefulness and with regular small snacks).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is equivalent to 4.8 ng/ml over the usual period of 8 h of sleep, representing an independent sleep/fasting-related fluctuation of 74% around the leptin mesor of 6.5 ng/ml (Fig. 3).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the subjects had a significant circadian rhythm in sOB-R, and there was no group mean circadian rhythm although a very small amplitude, approximately 12 h harmonic, was detected (P ϭ 0.04), presumably representing a small ultradian rhythm in sOB-R as shown in Fig. 2 (top right).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although all of these measurements were made during continued wakefulness, it can be seen that the endogenous circadian system caused a steady increase in leptin across the time that corresponds to the habitual sleep period in this group of subjects (with a peak just after the usual time of awakening, and a trough in the afternoon).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The peak-totrough amplitude of the circadian rhythms was approximately 22% for insulin (P ϭ 0.02) and 10% for glucose (P ϭ 0.001).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of fall of circulating leptin during sleep/fasting was almost identical in the baseline period and during recovery sleep (Fig. 3), despite improvements in average sleep efficiency (5.5% absolute increase; P Ͻ 0.01, paired t test), decreased sleep onset latency (13 min; not significant), and an average increase in nonrapid-eye-movement sleep stages III and IV (6.1% absolute increase; P Ͻ 0”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show that healthy humans do have an endogenous circadian rhythm of glucose and insulin, with a peak at the usual time of awakening, at a time similar to that of the circadian-related peak in leptin (Fig. 2).”
- Also stated in: § Discussion · plain
“There were significant circadian rhythms in circulating leptin, glucose, and insulin (left panels).”
- Also stated in: § Discussion · plain
“The circadian system caused a steady increase in leptin across the usual sleep period and increases in both insulin and glucose around the time of habitual awakening.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adiponectin concentrations were relatively stable, with only one subject showing an endogenous circadian rhythm, and there was no group mean circadian rhythm in adiponectin (Fig. 2, lower right).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the group, the circadian variation in circulating leptin was highly significant (P Ͻ 0.0001), with a peak-totrough value, over the 24 h, of 16% of the mesor.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the subjects had a significant circadian rhythm in sOB-R, and there was no group mean circadian rhythm although a very small amplitude, approximately 12 h harmonic, was detected (P ϭ 0.04), presumably representing a small ultradian rhythm in sOB-R as shown in Fig. 2 (top right).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“With sleep occurring at the usual phase of the circadian rhythm (left panel of Fig. 4), circadian and behavioral fluctuations are almost out of phase and cancel each other to a large extent: leptin reaches a peak during the usual sleep period, declines throughout the rest of the night, begins to increase throughout the morning, reaches a plateau for approximately 8 h during the daytime, and then”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma leptin levels were measured using a RIA (DSL) with a sensitivity of 0.5 ng/ml and intraassay CV of 8.3%.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma insulin was assayed using a commercially available paramagnetic-particle chemiluminescent immunoassay (Beckman Access B; Diamond Diagnostics, Holliston, MA) with a sensitivity of 0.03 IU/ml and an average intraassay CV of 3.1-5.6%.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Because adipokines play important physiological and pathophysiological roles in obesity and the metabolic syndrome (31), these findings may provide potentially important implications in situations when physiological behaviors and the circadian system become misaligned, such as with jet lag, shift work, or clinical conditions such as the nocturnal eating syndrome (32)(33)(34).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [31]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Core body temperature was recorded throughout using a rectal temperature sensor (Yellow Springs Instrument Co., Inc., Yellow Springs, OH) to provide a marker of the endogenous circadian pacemaker.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“There are day/night patterns in plasma leptin and adiponectin concentrations, with leptin rising (8 -12) and adiponectin falling during the night (13).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > L EPTIN AND ADIPONECTIN are adipocyte secreted
What the sources say
- Not checked yetcites [8]
- Not checked yetcites [9]
- Not checked yetcites [10]
- Not checked yetcites [11]
- Not checked yetcites [12]
- Not checked yetcites [13]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, this is presumably of little physiological consequence because only one of the six subjects had a significant linear decline in adiponectin across the constant routine.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
hedgedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma glucose was assayed using a commercially available assay (ACE glucose reagent; Alfa Wassermann, West Caldwell, NJ) with a sensitivity of 1 mg/dl and an average intraassay CV less than 2%.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This schedule was verified by time-logged telephone calls of bedtimes and waketimes for 2 wk as well as activity monitoring for 3-7 d (wrist-worn Actigraph; Ambulatory Monitoring, Ardsley, NY).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Protocol
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma adiponectin levels were measured using a RIA from Diagnostics Systems Laboratory (DSL, Webster, TX) with a sensitivity of 2 ng/ml and intraassay coefficient of variation (CV) of 6.6%.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because the circadian fluctuation in sOB-R was less than the fluctuation in total leptin, this implies that the biologically active free leptin had a circadian variation.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, these data suggest that the previously documented day/night pattern in leptin is caused by the combined effects of the endogenous circadian pacemaker and the day/night patterns in behaviors, with the latter having the greater effect across the 24-h cycle.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because adipokines play important physiological and pathophysiological roles in obesity and the metabolic syndrome (31), these findings may provide potentially important implications in situations when physiological behaviors and the circadian system become misaligned, such as with jet lag, shift work, or clinical conditions such as the nocturnal eating syndrome (32)(33)(34).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Leptin levels have a robust 24-h rhythm (8 -12), with leptin increasing monotonically from the morning through the afternoon and evening and peaking in the early part of the nocturnal sleep period.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [8]
- Not checked yetcites [9]
- Not checked yetcites [10]
- Not checked yetcites [11]
- Not checked yetcites [12]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All temperature, hormonal and glucose data collected in the first 5 h of the constant routine were excluded from analysis to avoid the effects of altered posture and sleep-wake transition.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Analysis of circadian rhythmicity and behavioral influences on glucose and hormones
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data imply that alterations in the sleep/wake schedule would lead to an increased daily range in circulating leptin, with lowest leptin upon awakening”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Abstract
hedgeddirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The constant routine protocol is designed to unmask underlying circadian rhythms as it reduces or eliminates other physiological influences from the environment, varied behaviors, large meals, and sleep.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Protocol
What the sources say
- Not checked yetcites [25]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma sOB-R levels were measured using a commercially available ELISA (DSL) with a sensitivity of 0.8 ng/ml and intraassay CV between 5.5 and 6.6%.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the subjects had a significant circadian rhythm in sOB-R, and there was no group mean circadian rhythm although a very small amplitude, approximately 12 h harmonic, was detected (P ϭ 0.04), presumably representing a small ultradian rhythm in sOB-R as shown in Fig. 2 (top right).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Circadian effects (independent from behavioral effects)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, leptin administration is also effective in regulating insulin resistance in hypoleptinemic states, including both congenital leptin deficiency and acquired states of leptin deficiency (1,31,49).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [1]
- Not checked yetcites [31]
- Not checked yetcites [49]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Our data imply that alterations in the sleep/wake schedule can lead to an increased peak-to-trough daily swing in the physiologically active circulating free leptin, which may influence food intake and energy balance and could thus be implicated in the increased obesity and cardiovascular disease in the shift work population (15).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [15]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
None of the sources cited for this claim have been checked yet.
In the paper
“Although common obesity is associated with hyperleptinemia in humans (44 -46), subjects with leptin receptor mutation(s), as well as hypoleptinemic subjects with either congenital or acquired leptin deficiency, are also obese (47-48).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [44]
- Not checked yetcites [45]
- Not checked yetcites [46]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, in this model, the person would awaken with a very low level of leptin, which would be expected to increase appetite and alter neuroendocrine function at this time (4, 43).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [4]
- Not checked yetcites [43]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The circadian and behavioral effects on the measured variables are additive.
None of the sources cited for this claim have been checked yet.
In the paper
“Although common obesity is associated with hyperleptinemia in humans (44 -46), subjects with leptin receptor mutation(s), as well as hypoleptinemic subjects with either congenital or acquired leptin deficiency, are also obese (47-48).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [47]
- Not checked yetcites [48]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“suggesting that their nocturnal eating could be a result of the absence of a nocturnal anorexic signal provided by leptin (14).”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [14]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These differences among studies suggest that the day/night pattern in adiponectin (13) in lean individuals is mainly attributable to day/night patterns in behaviors (sleep/fasting and wakefulness/meals) rather than the endogenous circadian cycle and that this effect can be observed in obese individuals.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
What the sources say
- Not checked yetcites [13]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The authors state this as an assumption.
The circadian component could be extrapolated from the constant routine data to the sleep periods on either side of the constant routine.
“Because circadian rhythmicity was calculated during the constant routine, this last analysis relied upon our assumption that the circadian component could be extrapolated from the constant routine data to the sleep periods on either side of the constant routine.”
The paper relies on this without support.
To the authors' knowledge, this study is the first to directly assess the independent influences of the endogenous circadian pacemaker and various physiological behaviors on adipocyte and glucose physiology using a validated circadian protocol.
“to our knowledge, this study is the first to directly assess the independent influences of the endogenous circadian pacemaker and various physiological behaviors on adipocyte and glucose physiology using a validated circadian protocol.”
The authors state this as an assumption.
The circadian and behavioral effects on the measured variables are additive.
“Limitations of the study include the fact that our separation of circadian and behavioral effects relies upon the assumption that these effects are additive, as suggested by the statistical analyses.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, glucose, insulin, cortisol, epinephrine, norepinephrine, and leptin display endogenous circadian variation (Morgan et al., 1998; Scheer et al., 2009, 2010; Shea et al., 2005; Van Cauter et al., 1994; Wehr et al., 2001).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Shea et al., 2005
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of wakefulness/meals (independent from circadian effects)
“The average increase was equivalent to 3.33 ng/ml over the usual period of 16 h of continuous wakefulness.”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Effect of sleep/fasting (independent from circadian effects)
“mean, ϩ0.21 mg/ml per hour, see above”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
“a similar study in obese subjects (average BMI, 57.5 kg/m 2 ) failed to demonstrate a similar day/night variation”
§ Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans > Discussion
“and that this effect can be observed in obese individuals.”
Citations
Cites
Impact of sleep debt on metabolic and endocrine function
Spiegel, K., Leproult, R., & Van Cauter, E. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01376-8 · Cited by 3,668
Diet-induced insulin resistance in mice lacking adiponectin/ACRP30
Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., et al. (2002) · Nature Medicine · doi:10.1038/nm724 · Cited by 2,114
Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency
Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M. A., & O'Rahilly, S. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909163411204 · Cited by 1,998
Methods for cosinor-rhythmometry.
Nelson, W. E., Tong, Y. L., Lee, J. K., & Franz Halberg, A. (1979) · PubMed · Cited by 1,701
Leptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · cited 1×
“In addition, leptin administration is also effective in regulating insulin resistance in hypoleptinemic states, including both congenital leptin deficiency and acquired states of leptin deficiency (1,31,49).”
BackgroundKarlsson, B., Knutsson, A., & Lindahl, B. (2001) · Occupational and Environmental Medicine · doi:10.1136/oem.58.11.747 · Cited by 924
Recombinant human leptin in women with hypothalamic amenorrhea
Welt, C. K., Chan, J. L., Bullen, J., Murphy, R., Smith, P., DePaoli, A. M., Karalis, A., & Mantzoros, C. S. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040388 · Cited by 908
Self-citationNocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects.
Sinha, M. K., Ohannesian, J. P., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Magosin, S., Marco, C. C., & Caro, J. F. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118551 · Cited by 780
Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle
Czeisler, C. A., Allan, J. S., Strogatz, S. H., Ronda, J. M., Sánchez, R., Ríos, C. D., Freitag, W. O., Richardson, G. S., & Kronauer, R. E. (1986) · Science · doi:10.1126/science.3726555 · Cited by 770 · cited 2×
“To overcome many of the limitations of previous studies, we made measurements throughout a protocol that permitted separation of endogenous circadian effects from systematic influences related to sleep or fasting and wakefulness or food intake by studying subjects: first, during sleep and fasting; second, throughout m…”
MethodChan, J. L., Heist, K., DePaoli, A. M., Veldhuis, J. D., & Mantzoros, C. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17490 · Cited by 697
Self-citation
Cited by
Sorted by citations
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351
Self-citationSleep curtailment is accompanied by increased intake of calories from snacks
Nedeltcheva, A. V., Kilkus, J. M., Imperial, J., Kasza, K., Schoeller, D. A., & Penev, P. D. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26574 · Cited by 717
Circadian regulation of glucose, lipid, and energy metabolism in humans
Poggiogalle, E., Jamshed, H., & Peterson, C. M. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.017 · Cited by 743
The role of insufficient sleep and circadian misalignment in obesity
Chaput, J., McHill, A. W., Cox, R. C., Broussard, J. L., Dutil, C., da Costa, B. G. G., Sampasa‐Kanyinga, H., & Wright, K. P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00747-7 · Cited by 733
Meal timing regulates the human circadian system
Wehrens, S. M. T., Christou, S., Isherwood, C., Middleton, B., Gibbs, M. A., Archer, S. N., Skene, D. J., & Johnston, J. D. (2017) · Current Biology · doi:10.1016/j.cub.2017.04.059 · Cited by 596
Metadata
- Authors
- Shea, S. A., Hilton, M. F., Orlova, C., Ayers, R. T., & Mantzoros, C. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Shea, Steven A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-05
- Volume
- 90
- Issue
- 5
- Pages
- 2537-2544
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2885832
- OpenAlex
- W2077495163
- Semantic Scholar
- 78d3fa1949c6630e0a7605ffdbbbdaf3318ad438
- Cited by
- 240
- References
- 58
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 14 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 14 · 2016: 18 · 2015: 14 · 2014: 12 · 2013: 11 · 2012: 17
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Brigham and Women's Hospital
- U.S. Public Health Service (R01 57875)
- National Heart, Lung, and Blood Institute (K24-HL76446, K24HL076446, R01HL076409, R01HL064815, R01 HL64815)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Research Resources (M01 RR 02635, M01RR002635)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- circadian rhythm, leptin, adiponectin, soluble leptin receptor, glucose, insulin, sleep-wake cycle, dietary intake, energy balance, obesity, shift work, constant routine, fasting
- MeSH terms
- Adult, Blood Glucose, Circadian Rhythm, Humans, Insulin, Male, Middle Aged, Obesity, Sleep, Wakefulness, Work Schedule Tolerance, Leptin, Intercellular Signaling Peptides and Proteins, Adiponectin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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