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Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans.
Open accessAbstract
Glucocorticoid concentrations vary throughout the day. To determine whether an increase in cortisol similar to that present during sleep is of physiologic significance in humans, we studied the disposition of a mixed meal when the nocturnal rise in cortisol was mimicked or prevented using metyrapone plus either a variable or constant hydrocortisone infusion. When glucose concentrations were matched with a glucose infusion, hepatic glucose release (2.6 +/- 0.2 vs. 1.5 +/- 0.4 nmol/kg per 6 h) was higher (P < 0.05) while glucose disappearance (5.9 +/- 0.3 vs. 7.3 +/- 0.9 mmol/kg per 6 h) and forearm arteriovenous glucose difference (64 +/- 24 vs. 231 +/- 62 mmol/dl per 6 h) were lower (P < 0.05) during the variable than basal infusion. The greater hepatic response during the variable cortisol infusion was mediated (at least in part) by inhibition of insulin and stimulation of glucagon secretion as reflected by lower (P < 0.05) C-peptide (0.29 +/- 0.01 vs. 0.38 +/- 0.04 mmol/liter per 6 h) and higher (P < 0.05) glucagon (42.7 +/- 2.0 vs. 39.3 +/- 1.8 ng/ml per 6 h) concentrations. In contrast, the decreased rates of glucose uptake appeared to result from a state of "physiologic" insulin resistance. The variable cortisol infusion also increased (P < 0.05) postprandial palmitate appearance as well as palmitate, beta-hydroxybutyrate, and alanine concentrations, suggesting stimulation of lipolysis, ketogenesis, and proteolysis. We conclude that the circadian variation in cortisol concentration is of physiologic significance in normal humans.
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TL;DR
In healthy humans, mimicking the nocturnal rise in cortisol with a variable hydrocortisone infusion raised fasting and postprandial glucose and altered postprandial carbohydrate, fat, and protein metabolism compared with a basal infusion. The effects were largely offset by compensatory hyperglycemia, except for increased palmitate appearance, suggesting the circadian cortisol rise is physiologically significant.
Key findings
- The variable cortisol infusion increased fasting glucose (95±2 vs. 88±2 mg/dl, P < 0.005) and postprandial glucose response (8.2±1.0 vs. 5.1±0.9 g/dl per 6 h), peak glucose (182±5 vs. 158±7 mg/dl), and nadir (90±2 vs. 77±4 mg/dl) versus basal cortisol (P < 0.01).
- When postprandial glucose concentrations were matched, hepatic glucose release was higher (2.6±0.2 vs. 1.5±0.4 nmol/kg per 6 h) while glucose disappearance (5.9±0.3 vs. 7.3±0.9 mmol/kg per 6 h) and forearm arteriovenous glucose difference (64±24 vs. 231±62 mmol/dl per 6 h) were lower during variable versus basal-plus-glucose infusion (P < 0.05).
- Matched-glucose studies showed lower C-peptide (0.29±0.01 vs. 0.38±0.04 mmol/liter per 6 h) and higher glucagon (42.7±2.0 vs. 39.3±1.8 ng/ml per 6 h) during variable cortisol, suggesting inhibited insulin and stimulated glucagon secretion.
- Variable cortisol also increased postprandial palmitate appearance and palmitate, β-hydroxybutyrate, and alanine concentrations, consistent with stimulated lipolysis, ketogenesis, and proteolysis.
Methods
- Ten healthy volunteers (5 males, 5 females; mean age 34±4 yr; mean BMI 22.7±0.8 kg/m²) were studied in random order on two occasions separated by at least 2 wk; endogenous cortisol secretion was blocked with metyrapone, and hydrocortisone was infused either at a constant basal rate or variably to mimic the nocturnal cortisol rise.
- A mixed meal (472 kcal; 45% carbohydrate, 40% fat, 15% protein) was given at 1000 with [2-³H]glucose and D-xylose; glucose turnover was measured with [6-³H]glucose and NaH¹⁴CO₃, and palmitate kinetics were measured in 5 volunteers.
- Six volunteers underwent a third study with basal hydrocortisone plus intravenous glucose to match postprandial glucose to the variable-cortisol study; postprandial responses were calculated as area above zero by trapezoidal rule, and paired t tests were used with P < 0.05 considered significant.
Limitations
- Stated: ¹⁴CO₂ incorporation into glucose provides only an index of gluconeogenesis because intramitochondrial specific activity is unknown, and precursor dilution may underestimate gluconeogenesis.
- Stated: alanine concentration changes could reflect altered de novo synthesis, utilization, or proteolytic release; palmitate appearance may only qualitatively estimate lipolysis and may miss fatty acids oxidized before systemic mixing.
- Stated and evident: the variable infusion peak cortisol (~20 µg/dl) was slightly higher than reported nocturnal values (~15–18 µg/dl), while the basal infusion rose to ~9 µg/dl, potentially over- and underestimating effects respectively; complete matched-glucose forearm and isotopic data were available in only five volunteers, and the study was acute and in normal humans only.
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49 Own result · 34 Own interpretation · 27 Not checked yet · 6 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
“Pre- meal palmitate concentrations (134±23 vs. 114±23 ,umol/ liter) and palmitate appearance (2.3±0.4 vs. 2.2±0.5 gmol/kg per min) did not differ (P = 0.4-0.8)during the variable and basal cortisol infusions (Fig. 6).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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In the paper
“The C-peptide response to meal ingestion was similar (0.30±0.02 vs. 0.28±0.02mmol/liter per 6 h) during the variable and basal cortisol infusions when glucose concen- trations were allowed to vary.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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In the paper
“Although premeal insulin concentrations did not differ amongst studies, the postprandial insulin response was slightly greater (P < 0.05) during the variable than during the basal cortisol infusion (Fig. 2).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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“Upon meal ingestion, total postprandial response (8.2±1.0 vs. 5.1±0.9g/dl per 6 h), peak glucose concentrations (182±5 vs. 158±7 mg/dl), and postprandial glucose nadir (90±2 vs. 77±4 mg/dl) also were higher (P < 0.01 ) during the variable than during the basal cortisol infusion.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
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“However when glucose concentrations were matched, both plasma alanine (126±9 vs. 101±6 mol/liter per 6 h) and fl-OHB (30±4 vs. 6±1 mmol/liter per 6 h) concentrations were higher (P < 0.05) during the variable than during the basal cortisol plus glucose study (Fig. 5).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However when the individual components of glucose appearance were compared, there was no detectable difference in the appearance ofingested glucose, hepatic glucose release or carbon dioxide incorporation into glucose during the variable and basal cortisol infusions (Fig. 3).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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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
“Pre- meal palmitate concentrations (134±23 vs. 114±23 ,umol/ liter) and palmitate appearance (2.3±0.4 vs. 2.2±0.5 gmol/kg per min) did not differ (P = 0.4-0.8)during the variable and basal cortisol infusions (Fig. 6).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The postprandial glucagon concentrations were similar during the variable and basal cortisol infusions (41.1±1.9 vs. 41.8±2.5 ng/ml per 6 h) when glucose concentrations were allowed to vary.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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In the paper
“However when the individual components of glucose appearance were compared, there was no detectable difference in the appearance ofingested glucose, hepatic glucose release or carbon dioxide incorporation into glucose during the variable and basal cortisol infusions (Fig. 3).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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“As shown in Fig. 1, fasting glucose concentrations were higher (P < 0.005) during the variable than during the basal cortisol infusion (95±2 vs. 88±2 mg/dl).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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“There also was no detectable difference in either glucose disappearance, or the arteriovenous difference of glucose across the forearm between studies (Fig. 4).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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“There also was no detectable difference in either glucose disappearance, or the arteriovenous difference of glucose across the forearm between studies (Fig. 4).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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“Overnight and postprandial growth hormone con- centrations did not differ between studies (data not shown).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plain- Asserted: passes — The authors put it forward as true.
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“Plasma D-xylose concentration, a marker of carbohydrate absorption, did not differ amongst studies (data not shown).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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“Lactate and alanine concentration increased and 13-OHB concentrations decreased after meal ingestion.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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“While the systemic rate of appearance of ingested glucose tended to be higher (and therefore initial splanchnic extraction lower) during the variable than during the basal cortisol plus glucose infusion, this difference did not reach statistical signifi- cance.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedged- Asserted: passes — The authors put it forward as true.
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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
“While the systemic rate of appearance of ingested glucose tended to be higher (and therefore initial splanchnic extraction lower) during the variable than during the basal cortisol plus glucose infusion, this difference did not reach statistical signifi- cance.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Our data showing increased palmitate flux and increased alanine concentrations are consistent with these pos- sibilities.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Taken together these data indicate an inhibitory effect of the variable cortisol infusion on insulin secretion and a stimula- tory effect on glucagon secretion.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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In the paper
“The present studies extend these observations by demonstrating that cortisol, in concentrations that mimic those normally present in healthy humans during sleep, increased both fasting and postprandial glucose concentrations.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
boosteddirectn = 5 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“Glucocorticoids are potent regulators of carbohydrate, fat, and protein metabolism ( 1, 2).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Introduction
What the sources say
- Not checked yetcites [1]
- Not checked yetcites [2]
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“The concomitant increase in plasma alanine and fl-OHB concentrations suggests enhanced proteolysis and ketogenesis whereas the increase in palmitate concentration and appearance indicates enhanced adipose tis- sue lipolysis.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedgedconditionaln = 5 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“The most marked increase in cortisol in healthy subjects generally occurs from the middle ofthe night to breakfast time with similar but less consistent increases also being observed after food ingestion ( 11).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Introduction
What the sources say
- Not checked yetcites [11]
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Cortisol increased glucose concentra- tion by stimulating hepatic glucose output and by inhibiting muscle glucose uptake.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
plaindirectn = 5 ·- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“This is not particularly surprising, since the portal to peripheral glucose gradient appears to have a greater effect on hepatic glucose uptake than does the portal insulin concentration (52,53).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [52]
- Not checked yetcites [53]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“enhanced responses to intravenous arginine (50).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [50]
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The observation that glucose tolerance is worse when a meal is eaten later in the day than when the same meal is eaten in the morning is well established (60, 61).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [60]
- Not checked yetcites [61]
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“If degradation to mono-or diglycerides is followed by reesterification this will result in release of free fatty acids into the circulation in the absence of net lipolysis (27).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [27]
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition to reducing its own endogenous production of glucose, the liver also contributes to postprandial carbohydrate tolerance by extracting a portion of the ingested glucose as it travels from the gut to the systemic circulation ( 5 1 ).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [51]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Presumably during long-term gluco-- corticoid excess this inhibitory effect is offset by chronic hyper- glycemia (41 ).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [41]
hedgeddirect- Asserted: passes — The authors put it forward as true.
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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
“In theory, pal- mitate appearance may only provide a qualitative estimate of lipolysis.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedged- Asserted: passes — The authors put it forward as true.
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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
“Cortisol could have increased hepatic glucose produc- tion by at least three mechanisms.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“However, since it is likely that lipolysis and proteolysis ifanything were greater during the variable than basal cortisol infusion, this would result in a con- servative error since we observed higher rates ofgluconeogene- sis with the variable cortisol study.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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. It may state two separate claims as one.
In the paper
“With regard to our measures of proteolysis and lipolysis, a change in alanine concentration could be due to a change in de novo alanine synthesis from pyruvate, a decrease in alanine utilization and/or release dur- ing proteolysis (56).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [56]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“With regard to our measures of proteolysis and lipolysis, a change in alanine concentration could be due to a change in de novo alanine synthesis from pyruvate, a decrease in alanine utilization and/or release dur- ing proteolysis (56).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [56]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“First, cortisol could increase the concentration as well as the activity of enzymes in the glu- coneogenic and glycogenolytic pathways ( 1, 2).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [1]
- Not checked yetcites [2]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Glucocorti- coid excess can increase glycogen synthesis in the fasting state ( 1,2).”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
What the sources say
- Not checked yetcites [1]
- Not checked yetcites [2]
plainconditional- 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
“One would therefore anticipate that a hormone whose primary role is to antagonize insulin action would not impact on this process.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
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.
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 corti- sol-induced increase in palmitate, d-OH butyrate and alanine concentrations are consistent with additional effects on lipolysis, ketogenesis, and perhaps proteolysis.”
§ Metabolic Effects of the Nocturnal Rise in Cortisol on Carbohydrate Metabolism in Normal Humans > Results
hedgedconditional- 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.
The paper relies on this without support.
It is unknown whether the normal variations in cortisol are of physiologic significance in normal humans.
“It is currently unknown whether these variations in cortisol are of physiologic significance in normal humans.”
The paper relies on this without support.
The basal hydrocortisone infusion (0.3 μg/kg/min) is an adequate control for the absence of the nocturnal rise in cortisol.
“On the other hand, the basal infusion was accompanied by a slight but consistent increase in cortisol to -9 jug/dl.”
The paper relies on this without support.
Matching postprandial glucose concentrations with a glucose infusion isolates the direct effects of cortisol from those due to compensatory increases in glucose concentration.
“These latter studies permitted us to differentiate the direct effects of cortisol from those due to compensa- tory increases in glucose concentration.”
The paper relies on this without support.
The forearm arteriovenous glucose difference reflects muscle glucose uptake.
“The decrease in extraction ofglucose across the forearm implies that skeletal muscle participates in this response.”
The paper relies on this without support.
D-xylose concentration is a valid marker of carbohydrate absorption.
“Plasma D-xylose concentration, a marker of carbohydrate absorption, did not differ amongst studies (data not shown).”
The authors state this as an assumption.
C-peptide and glucagon clearance remained constant on the two study days.
“Assuming that C- peptide and glucagon clearance remained constant on the two study days”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Glucocorticoids are critical regulators of energy balance; however, their complex effects on fuel metabolism are highly context‐dependent, are not linear in their dose response and are influenced by factors such as the diurnal rhythm.1”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [1]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Two studies have examined the effect of physiological cortisol concentrations on in vivo lipolysis and had conflicting results in the fasted state;1, 10”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“however, neither study used a pancreatic clamp to control counter‐regulatory hormones.”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [1]
In the citing paper
“Cortisol impairs insulin sensitivity with a latency of four to six hours.56,58,59”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [59]
Citations
Cites
Coated Charcoal Immunoassay of Insulin
Herbert, V. D., Lau, K., Gottlieb, C. W., & Bleicher, S. J. (1965) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-25-10-1375 · Cited by 2,969
Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects
WEITZMAN, E. D., FUKUSHIMA, D., NOGEIRE, C., ROFFWARG, H., GALLAGHER, T. F., & HELLMAN, L. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-1-14 · Cited by 1,258
Hormone-fuel interrelationships during fasting.
Cahill, G. F., Herrera, M. G., Morgan, A. P., Soeldner, J. S., Steinke, J., Levy, P. L., Reichard, G. A., & Kipnis, D. M. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105481 · Cited by 1,036
Measurement of Size and Turnover Rate of Body Glucose Pool by the Isotope Dilution Method
Steele, R., Wall, J. S., de Bodo, R. C., & Altszuler, N. (1956) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1956.187.1.15 · Cited by 816
RIZZA, R. A., MANDARINO, L. J., & GERICH, J. E. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-1-131 · Cited by 696 · cited 5×
“Enhanced hepatic glucose release during the nocturnal rise in cortisol is consistent with what would be predicted from previous experiments using supraphysiologic concentrations of cortisol (5-8).”
BackgroundResultInfluentialSelf-citationON THE HORMONAL REGULATION OF CARBOHYDRATE METABOLISM; STUDIES WITH C14 GLUCOSE.
DeBodo, R. C., Steele, R., ALTSZULER, N., Dunn, A., & Bishop, J. (1963) · PubMed · Cited by 532
Regulation of Splanchnic and Peripheral Glucose Uptake by Insulin and Hyperglycemia in Man
DeFronzo, R. A., Ferrannini, E., Hendler, R., Felig, P., & Wahren, J. (1983) · Diabetes · doi:10.2337/diab.32.1.35 · Cited by 509
Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep
Van Cauter, E., Blackman, J. D., Roland, D., Spire, J. P., Refetoff, S., & Polonsky, K. S. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115396 · Cited by 448
Role of Glucagon, Catecholamines, and Growth Hormone in Human Glucose Counterregulation
Rizza, R. A., Cryer, P. E., & Gerich, J. E. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109464 · Cited by 421
Self-citationEffects of glucocorticoids on carbohydrate metabolism
Mcmahon, M., Gerich, J., & Rizza, R. (1988) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610040105 · Cited by 390
Self-citation
Research works printed but not linked: 1
- Faloona, G., and R. Unger. 1974. Glucagon. In Methods of Hormone Radioimmunoassay. B. Jaffe and H. Behrman, editors. Academic Press, Inc., New York. 317-330.
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
“4 Lower Right panel) could contribute to insulin resistance and hyperglycemia (13, 14).”
BackgroundThe dark side of light at night: physiological, epidemiological, and ecological consequences
Navara, K. J., & Nelson, R. J. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00473.x · Cited by 795
“In many species, including some birds, rodents, fish, and humans, for example, circulating concentrations of sex steroids [9–11] and glucocorticoids [12] vary with the light/dark cycle throughout the day, causing corresponding changes in reproductive activities [13] and metabolic functions [14].”
BackgroundRegulation of glucose homeostasis by glucocorticoids
Kuo, T., McQueen, A., Chen, T.-C., & Wang, J.-C. (2015) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-2895-8_5 · Cited by 723
Glucocorticoids and insulin resistance: old hormones, new targets
ANDREWS, R. C., & WALKER, B. R. (1999) · Clinical Science · doi:10.1042/cs0960513 · Cited by 731
Roles of Circadian Rhythmicity and Sleep in Human Glucose Regulation
Cauter, E. V., Polonsky, K. S., & Scheen, A. J. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.5.0317 · Cited by 632
“Indeed, the immediate effect of an increase in plasma cortisol level, even of very small amplitude, was an abrupt inhibition of insulin secretion without change in glucose concentration, consistent with previous in vitro (59–63) and in vivo (57, 64, 65) studies that have shown that glucocorticoids may have a direct im…”
BackgroundResult
Metadata
- Authors
- Dinneen, S., Alzaid, A., Miles, J., & Rizza, R.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Dinneen, S
- Venue
- Journal of Clinical Investigation
- Published
- 1993-11-01
- Volume
- 92
- Issue
- 5
- Pages
- 2283-2290
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288409
- OpenAlex
- W1969547717
- Cited by
- 175
- References
- 71
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 12 · 2013: 4 · 2012: 9
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institutes of Health (7r01dk038092-09, RR-00585)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK38092, DK 29953)
- National Center for Research Resources (RR-00585, M01RR000585)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- diurnal cortisol rhythm, glucocorticoids, carbohydrate metabolism, hepatic glucose production, glucose disposal, insulin resistance, insulin inhibition, glucagon secretion, C-peptide, mixed meal, metyrapone, lipolysis, ketogenesis, proteolysis, postprandial lipemia
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Female, Glucagon, Humans, Hydrocortisone, Infusions, Intravenous, Insulin, Male, Metyrapone, Palmitates, Periodicity, Sleep, Carbohydrate Metabolism
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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