Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury

Wolahan, Stephanie M.; Prins, Mayumi L.; McArthur, David L.; Real, Courtney; Hovda, David A.; Martin, Neil A.; Vespa, Paul; Glenn, Thomas C.

doi:10.1007/s12028-016-0313-3

Cited by 9 publications

(6 citation statements)

References 40 publications

(46 reference statements)

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“…The data contrast with a previous pilot crossover RCT performed in critically ill adults, which found increased ketone concentrations by tight glucose control [ 15 ]. However, in this crossover RCT, patients received significantly less nutritional intake while receiving tight glucose control, which may have confounded the results.…”

Section: Discussioncontrasting

confidence: 99%

“…Moreover, elevated glucose concentrations may suppress lipolysis and subsequent ketogenesis, whereas lowering blood glucose concentrations could reduce suppression of ketogenesis [ 6 , 11 ]. In this regard, a pilot crossover RCT in critically ill adults found activated ketogenesis by lowering blood glucose with insulin therapy [ 15 ]. However, in this crossover study, patients received significantly less feeding in periods on tight glucose control, which may have confounded the results.…”

Section: Introductionmentioning

confidence: 99%

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Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

et al. 2021

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Background Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis. Methods This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test. Results In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1–3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1–3 and significantly lower than the ICU admission values for both groups (P < 0.0001). Conclusion Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

et al. 2021

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“…Additional factors that might trigger brain KB at the acute phase of TBI First, we found a significant inverse correlation between acute fasted brain KB and blood glucose -but not brain glucose -supporting the fact that limited glucose availability is an important systemic driver of ketone production at the acute phase of TBI. 39 We also identified a significant positive correlation between acute fasted cerebral KB levels and patient age. Our data are in line with previous observations in healthy subjects, showing increased cerebral ketone metabolism secondary to reduced glucose metabolism with advancing age, 40 whereby increased brain KB compensate for glucose shortage by the aging brain.…”

Section: Modulation Of Brain Kb By Nutritional Ketosismentioning

confidence: 59%

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Bernini

Masoodi

Solari

et al. 2018

J Cereb Blood Flow Metab

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Adaptive metabolic response to injury includes the utilization of alternative energy substrates -such as ketone bodies (KB) -to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n ¼ 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and b-hydroxybutyrate). Nutrition -from fasting vs. stable nutrition state -was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] mmol/L vs. 13.1 [6.5-64.3] mmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] mmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p ¼ 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.

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“…al. (Gowda et al, 2010) and had been published previously (Wolahan et al, 2016). Following solvent removal, plasma samples were reconstituted in 650 μL of 0.1 M phosphate buffered solution in deuterium oxide at pH 7.4, prepared with 0.1 mM 13 C-labeled sodium formate (isotopic enrichment 99%, Cambridge Isotope Laboratories, Andover, MA) as an NMR internal standard.…”

Section: Methodsmentioning

confidence: 98%

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

Wolahan

Mao

Real

et al. 2017

J of Neuroscience Research

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Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant Sodium L-Lactate infusion in eleven moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of Sodium L-Lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from 0.92 to 1.84 mM) results in an increase in AVDlac from −0.078 mM to 0.090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury.

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Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury

Cited by 9 publications

References 40 publications

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

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