Liam McKeever1, Sarah J Peterson2, Omar Lateef2, Sally Freels3, Alan M Diamond4, Carol A Braunschweig5. 1. Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 2. Department of Clinical Nutrition, Rush University Medical Center, Chicago, Illinois, USA. 3. Department of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois, USA. 4. Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, USA. 5. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.
Abstract
BACKGROUND: Converting nutrition support to energy results in mitochondrial free radical production, possibly increasing oxidative stress. Highly prevalent single nucleotide variants (SNV) exist for the genes encoding antioxidant enzymes responsible for the detoxification of reactive oxygen species. Our objective was to explore the interaction between nutrition support and genetic SNV's for two anti-oxidant proteins (rs4880 SNV for manganese superoxide dismutase and rs1050450 SNV for glutathione peroxidase 1) on oxidative stress and secondarily on intensive care unit (ICU) mortality. METHODS: We performed a post-hoc analysis on 34 mechanically ventilated sepsis patients from a randomized control feeding trial. Participants were dichotomized into those who carried both the rs4880 and the rs1050450 at-risk alleles (Risk Group) versus all others (Nonrisk Group). We explored the interaction between genotype and percent time spent in the upper median of energy exposure on oxidative stress and ICU mortality. RESULTS: Adjusting for confounders, the slope of log F2-isoprostane levels across percentage of days spent in the upper median of daily kilocalories per kilogram (kcal/kg) was 0.01 higher in the Risk Group compared to the Non-Risk Group (p=0.01). Every 1 percent increase in days spent in the upper median of daily kcal/kg was associated with an adjusted 10.3 percent increased odds of ICU mortality amongst participants in the Risk Group (odds ratio [OR]=1.103, p=0.06) but was highly insignificant in the Nonrisk group (OR=0.991, P=0.79). CONCLUSION: Nutrition support may lead to increased oxidative stress and worse clinical outcomes in a large percent of ICU patients with an at-risk genotype.
BACKGROUND: Converting nutrition support to energy results in mitochondrial free radical production, possibly increasing oxidative stress. Highly prevalent single nucleotide variants (SNV) exist for the genes encoding antioxidant enzymes responsible for the detoxification of reactive oxygen species. Our objective was to explore the interaction between nutrition support and genetic SNV's for two anti-oxidant proteins (rs4880 SNV for manganese superoxide dismutase and rs1050450 SNV for glutathione peroxidase 1) on oxidative stress and secondarily on intensive care unit (ICU) mortality. METHODS: We performed a post-hoc analysis on 34 mechanically ventilated sepsis patients from a randomized control feeding trial. Participants were dichotomized into those who carried both the rs4880 and the rs1050450 at-risk alleles (Risk Group) versus all others (Nonrisk Group). We explored the interaction between genotype and percent time spent in the upper median of energy exposure on oxidative stress and ICU mortality. RESULTS: Adjusting for confounders, the slope of log F2-isoprostane levels across percentage of days spent in the upper median of daily kilocalories per kilogram (kcal/kg) was 0.01 higher in the Risk Group compared to the Non-Risk Group (p=0.01). Every 1 percent increase in days spent in the upper median of daily kcal/kg was associated with an adjusted 10.3 percent increased odds of ICU mortality amongst participants in the Risk Group (odds ratio [OR]=1.103, p=0.06) but was highly insignificant in the Nonrisk group (OR=0.991, P=0.79). CONCLUSION: Nutrition support may lead to increased oxidative stress and worse clinical outcomes in a large percent of ICU patients with an at-risk genotype.
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