Glucose and lactate kinetics in children with severe malaria.

Children with severe malaria often present with lactic acidosis and hypoglycemia. Although both complications independently predict mortality, mechanisms underlying their development are poorly understood. To study these metabolic derangements we sequentially allocated 21 children with falciparum ma...

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Main Authors: Agbenyega, T, Angus, B, Bedu-Addo, G, Baffoe-Bonnie, B, Guyton, T, Stacpoole, P, Krishna, S
Format: Journal article
Language:English
Published: 2000
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author Agbenyega, T
Angus, B
Bedu-Addo, G
Baffoe-Bonnie, B
Guyton, T
Stacpoole, P
Krishna, S
author_facet Agbenyega, T
Angus, B
Bedu-Addo, G
Baffoe-Bonnie, B
Guyton, T
Stacpoole, P
Krishna, S
author_sort Agbenyega, T
collection OXFORD
description Children with severe malaria often present with lactic acidosis and hypoglycemia. Although both complications independently predict mortality, mechanisms underlying their development are poorly understood. To study these metabolic derangements we sequentially allocated 21 children with falciparum malaria and capillary lactate concentrations of 5 mmol/L or more to receive either quinine or artesunate as antimalarial therapy, and dichloroacetate or saline placebo for lactic acidosis. We then administered a primed infusion (90 min) of L-[3-13C1]sodium lactate and D-[6,6-D2]glucose to determine the kinetics of these substrates. The mean (SD) glucose disposal rate in all patients was 56 (16) micromol/kg x min, and the geometric mean (range) lactate disposal rate was 100 (66-177) micromol/kg x min. Glucose and lactate disposal rates were positively correlated (r = 0.62; P = 0.005). Artesunate was associated with faster parasite clearance, lower insulin/glucose ratios, and higher glucose disposal rates than quinine. Lactate disposal was positively correlated with plasma lactate concentrations (r = 0.66; P = 0.002) and time to recovery from coma (r = 0.82; P < 0.001; n = 15). Basal lactate disposal rates increased with dichloroacetate treatment. Elevated glucose turnover in severe malaria mainly results from enhanced anaerobic glycolysis. Quinine differs from artesunate in its effects on glucose kinetics. Increased lactate production is the most important determinant of lactic acidosis.
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spelling oxford-uuid:cc411466-b5b0-46fe-b81f-59c917e1ecc62022-03-27T07:20:33ZGlucose and lactate kinetics in children with severe malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cc411466-b5b0-46fe-b81f-59c917e1ecc6EnglishSymplectic Elements at Oxford2000Agbenyega, TAngus, BBedu-Addo, GBaffoe-Bonnie, BGuyton, TStacpoole, PKrishna, SChildren with severe malaria often present with lactic acidosis and hypoglycemia. Although both complications independently predict mortality, mechanisms underlying their development are poorly understood. To study these metabolic derangements we sequentially allocated 21 children with falciparum malaria and capillary lactate concentrations of 5 mmol/L or more to receive either quinine or artesunate as antimalarial therapy, and dichloroacetate or saline placebo for lactic acidosis. We then administered a primed infusion (90 min) of L-[3-13C1]sodium lactate and D-[6,6-D2]glucose to determine the kinetics of these substrates. The mean (SD) glucose disposal rate in all patients was 56 (16) micromol/kg x min, and the geometric mean (range) lactate disposal rate was 100 (66-177) micromol/kg x min. Glucose and lactate disposal rates were positively correlated (r = 0.62; P = 0.005). Artesunate was associated with faster parasite clearance, lower insulin/glucose ratios, and higher glucose disposal rates than quinine. Lactate disposal was positively correlated with plasma lactate concentrations (r = 0.66; P = 0.002) and time to recovery from coma (r = 0.82; P < 0.001; n = 15). Basal lactate disposal rates increased with dichloroacetate treatment. Elevated glucose turnover in severe malaria mainly results from enhanced anaerobic glycolysis. Quinine differs from artesunate in its effects on glucose kinetics. Increased lactate production is the most important determinant of lactic acidosis.
spellingShingle Agbenyega, T
Angus, B
Bedu-Addo, G
Baffoe-Bonnie, B
Guyton, T
Stacpoole, P
Krishna, S
Glucose and lactate kinetics in children with severe malaria.
title Glucose and lactate kinetics in children with severe malaria.
title_full Glucose and lactate kinetics in children with severe malaria.
title_fullStr Glucose and lactate kinetics in children with severe malaria.
title_full_unstemmed Glucose and lactate kinetics in children with severe malaria.
title_short Glucose and lactate kinetics in children with severe malaria.
title_sort glucose and lactate kinetics in children with severe malaria
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