Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans.

Dinneen, Seán F.; Alzaid, Aus; Miles, John M.; Rizza, R.

doi:10.1172/jci116832

Cited by 153 publications

(125 citation statements)

References 62 publications

(68 reference statements)

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“…The abnormally high cortisol at the end of the wake episode and beginning of the sleep episode when misaligned (Fig. 4 Lower Right panel) could contribute to insulin resistance and hyperglycemia (13,14). Also, decreased leptin stimulates appetite and decreases energy expenditure, which-if maintained chronically-could contribute to the development of obesity.…”

Section: Discussionmentioning

confidence: 99%

Adverse metabolic and cardiovascular consequences of circadian misalignment

Scheer

Hilton

Mantzoros

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,843

1,489

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There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/ feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h ''day.'' Subjects ate 4 isocaloric meals each 28-h ''day.'' For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling Ϸ1,000 assays/ subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept Ϸ12 h out of phase from their habitual times, systematically decreased leptin (؊17%, P < 0.001), increased glucose (؉6%, P < 0.001) despite increased insulin (؉22%, P ‫؍‬ 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (؉3%, P ‫؍‬ 0.001), and reduced sleep efficiency (؊20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work. autonomic nervous system ͉ diabetes ͉ glucose metabolism ͉ leptin ͉ obesity A pproximately 8.6 million Americans perform shift work (1), which is associated with increased risk of obesity, diabetes, and cardiovascular disease (2-6). The endogenous circadian timing system, including the suprachiasmatic nucleus (SCN) in the hypothalamus and peripheral oscillators in vital organs, optimally regulates much of our physiology and behavior across the 24-h day when it is properly aligned with the sleep/wake cycle. However, shift work is generally associated with chronic misalignment between the endogenous circadian timing system and the behavioral cycles, including sleep/wake and fasting/ feeding cycles (7,8). Shift workers often experience symptoms akin to jet lag, with gastrointestinal complaints, fatigue, and sleepiness during the scheduled wake periods, and poor sleep during the daytime sleep attempts (9). Moreover, chronic circadian misalignment has been proposed to be the underlying cause for the adverse metabolic and cardiovascular health effects of shift work (10, 11). The SCN regulates circadian rhythms in leptin, plasma glucose, glucose tolerance, corticosteroids, and ...

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Section: Discussionmentioning

confidence: 99%

Adverse metabolic and cardiovascular consequences of circadian misalignment

Scheer

Hilton

Mantzoros

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,843

1,489

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“…The circadian rhythm in cortisol is also unlikely to explain the lower glucose tolerance in the biological evening because cortisol, which decreases glucose tolerance (41,42), actually peaks in the biological morning and is low in the biological evening (10,15). Raised FFA levels can impair glucose tolerance and decrease insulin sensitivity and glucose oxidation (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the higher fasting and postprandial FFA levels before and after dinner could help explain why glucose tolerance and our estimate of insulin sensitivity were lower at dinner time. Cortisol can decrease glucose uptake and decrease insulin sensitivity (41,42). There is a behavioral cycle influence on cortisol (although the effect is much smaller than the endogenous circadian system's influence), with levels being lower before dinner than breakfast (10,15).…”

Section: Discussionmentioning

confidence: 99%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

351

336

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Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/ feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show-by using two 8-d laboratory protocols-in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower earlyphase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.circadian disruption | shift work | night work | glucose metabolism | diabetes I n healthy humans, there is a strong time-of-day variation in glucose tolerance, with a peak in the morning and a trough in the evening and night (1-6). Understanding the underlying mechanisms of the day/night variation in glucose tolerance is important for diurnally active individuals as well as shift workers, who are at increased risk for developing type 2 diabetes (7-9). The endogenous circadian system and circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles) have been shown to affect glucose metabolism (4,(10)(11)(12)(13)(14). However, the relative and separate importance of the endogenous circadian system and circadian misalignment-after accounting for behavioral cycle effects (including the sleep/wake, fasting/feeding, and physical inactivity/activity cycles, etc.)-on 24-h variation in glucose tolerance is not well understood.Most species have evolved an endogenous circadian timing system that optimally times physiological variations and behaviors relative to the 24-h environmental cycle (15-17). The mammalian circadian system is comp...

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“…Cortisol impairs insulin-induced suppression of endogenous glucose production (49). However, cortisol (50) enhances rather than suppresses hepatic glycogen synthesis (51,52).…”

Section: Discussionmentioning

confidence: 99%

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

Vella¹,

Shah²,

Basu³

et al. 2001

Diabetes

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In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at ϳ5.5 mmol/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3 H]glucose) was infused via an intraduodenal tube at a rate of 20 mol ⅐ kg ؊1 ⅐ min ؊1 . Insulin concentrations were increased to ϳ500 pmol/l while glucose was clamped at ϳ8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2 H 2 ]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P ‫؍‬ 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 ؎ 1.5 vs. 4.8 ؎ 0.8 mol ⅐ kg ؊1 ⅐ min ؊1 ). On the other hand, flux through the hepatic uridine-diphosphate-glucose pool did not differ between study days (14.2 ؎ 5.5 vs. 13.0 ؎ 4.2 mol ⅐ kg ؊1 ⅐ min ؊1 ), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 ؎ 2.9 vs. 1.3 ؎ 1.4 mol ⅐ kg ؊1 ⅐ min ؊1 ), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 ؎ 10.0 vs. 69.3 ؎ 6.3 mol ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes. Diabetes 50: 565-572, 2001 G lucagon-like peptide-1(7-36)-amide (GLP-1) and its analogues are being actively evaluated as a potential therapy for humans with type 1 diabetes (1-5). GLP-1 enhances insulin secretion, decreases glucagon secretion, and delays gastric emptying (6,7). In vitro studies also suggest that GLP-1 may have extrapancreatic effects (8,9). GLP-1 receptors are present in muscle (10,11), fat (8,12), and liver (13). In vitro studies have shown that GLP-1 can increase glucose uptake in each of these tissues and that its effects are additive to those of insulin (14,15). In contrast, results from in vivo studies have been less consistent. GLP-1 has been reported to increase glucose uptake during hyperglycemia and hyperinsulinemia in diabetic rats (16) and pancreatectomized dogs (17) and during euglycemia and hyperinsulinemia in humans with type 1 diabetes (18). On the other hand, GLP-1 has been reported to have no effect on insulin action during euglycemia and hyperinsulinemia in nondiabetic humans (19) and dogs (20) or during "prandial" insulin and glucose infusions in humans with type 2 diabetes (21).All of these studies evaluated insulin action during intravenous glucose infusion. This approach contrasts with the situation that occurs und...

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Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans.

Cited by 153 publications

References 62 publications

Adverse metabolic and cardiovascular consequences of circadian misalignment

Adverse metabolic and cardiovascular consequences of circadian misalignment

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

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