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Glucose and lactate kinetics in children with severe malaria
T Agbenyega1, B J Angus, G Bedu-Addo
1Department of Physiology, University of Science and Technology, School of Medical Sciences, Kumasi, Ghana.
Insights
Severe malaria in children causes lactic acidosis and hypoglycemia. This study found increased lactate production is the main cause of lactic acidosis, with glucose and lactate disposal rates correlating with recovery.
Area of Science:
- Biochemistry
- Infectious Diseases
- Pediatrics
Background:
- Severe malaria in children frequently involves lactic acidosis and hypoglycemia.
- These metabolic derangements are significant predictors of mortality but their mechanisms remain unclear.
Purpose of the Study:
- To investigate the metabolic derangements, specifically lactic acidosis and hypoglycemia, in children with severe malaria.
- To compare the effects of artesunate versus quinine and dichloroacetate versus placebo on glucose and lactate kinetics.
Main Methods:
- Sequential allocation of 21 children with severe malaria to receive either quinine or artesunate and dichloroacetate or saline placebo.
- Administration of stable isotope tracers (L-[3-13C1]sodium lactate and D-[6,6-D2]glucose) to determine substrate kinetics.
- Measurement of glucose and lactate disposal rates, parasite clearance, and clinical recovery parameters.
Main Results:
- Glucose and lactate disposal rates were positively correlated (r = 0.62; P = 0.005).
- Artesunate treatment was associated with faster parasite clearance, lower insulin/glucose ratios, and higher glucose disposal rates compared to quinine.
- Lactate disposal rates correlated positively with plasma lactate concentrations (r = 0.66; P = 0.002) and time to coma recovery (r = 0.82; P < 0.001).
Conclusions:
- Elevated glucose turnover in severe malaria is primarily driven by enhanced anaerobic glycolysis.
- Antimalarial drug choice (artesunate vs. quinine) impacts glucose kinetics.
- Increased lactate production is the principal determinant of lactic acidosis in severe malaria.
Abstract:
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.