This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agbenyega, T. Articles by Krishna, S. Search for Related Content PubMed PubMed Citation Articles by Agbenyega, T. Articles by Krishna, S.

Glucose and Lactate Kinetics in Children with Severe Malaria¹

Department of Physiology, University of Science and Technology, School of Medical Sciences (T.A.), and Departments of Child Health and Medicine, Komfo-Anokye Teaching Hospital (T.A., G.B-A., B.B.-B., S.K.), Kumasi, Ghana; Department of Infectious Diseases, St. George’s Hospital Medical School (B.J.A., S.K.), SW17 ORE London, United Kingdom; Wellcome-Mahidol Oxford Tropical Medicine Research Program, Mahidol University (B.J.A.), Bangkok 10400, Thailand; and Departments of Anesthesiology (T.G.) and Medicine, Biochemistry, and Molecular Biology (P.W.S.), University of Florida College of Medicine, Gainesville, Florida 32610-0226

Address all correspondence and requests for reprints to: Dr. Sanjeev Krishna, Department of Infectious Diseases, St. George’s Hospital Medical School, Cranmer Terrace, SW17 ORE London, United Kingdom. E-mail: s.krishna{at}sghms.ac.uk

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) µmol/kg·min, and the geometric mean (range) lactate disposal rate was 100 (66–177) µmol/kg·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.

This article has been cited by other articles:

				W. Zijlmans, A. van Kempen, M. Ackermans, J. de Metz, P. Kager, and H. Sauerwein Glucose Kinetics during Fasting in Young Children with Severe and Non-severe Malaria in Suriname Am J Trop Med Hyg, October 1, 2008; 79(4): 605 - 612. [Abstract] [Full Text] [PDF]

				M. D. Rozier, V. J. Zata, and M. L. Ellsworth Lactate interferes with ATP release from red blood cells Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3038 - H3042. [Abstract] [Full Text] [PDF]

				M. Jia, B. Coats, M. Chadha, B. Frentzen, J. Perez-Rodriguez, P. A. Chadik, R. A. Yost, G. N. Henderson, and P. W. Stacpoole Human Kinetics of Orally and Intravenously Administered Low-Dose 1,2-13C-Dichloroacetate. J. Clin. Pharmacol., December 1, 2006; 46(12): 1449 - 1459. [Abstract] [Full Text] [PDF]

				C J Woodrow, R K Haynes, and S Krishna Artemisinins Postgrad. Med. J., February 1, 2005; 81(952): 71 - 78. [Abstract] [Full Text] [PDF]

				P. W. Stacpoole, N. V. Nagaraja, and A. D. Hutson Efficacy of Dichloroacetate as a Lactate-Lowering Drug J. Clin. Pharmacol., July 1, 2003; 43(7): 683 - 691. [Abstract] [Full Text] [PDF]

				T. Agbenyega, T. Planche, G. Bedu-Addo, D. Ansong, A. Owusu-Ofori, V. A. Bhattaram, N. V. Nagaraja, A. L. Shroads, G. N. Henderson, A. D. Hutson, et al. Population Kinetics, Efficacy, and Safety of Dichloroacetate for Lactic Acidosis Due to Severe Malaria in Children J. Clin. Pharmacol., April 1, 2003; 43(4): 386 - 396. [Abstract] [Full Text] [PDF]

				C. Nealon, A. Dzeing, U. Muller-Romer, T. Planche, V. Sinou, M. Kombila, P. G. Kremsner, D. Parzy, and S. Krishna Intramuscular Bioavailability and Clinical Efficacy of Artesunate in Gabonese Children with Severe Malaria Antimicrob. Agents Chemother., December 1, 2002; 46(12): 3933 - 3939. [Abstract] [Full Text] [PDF]

				J. T. Daugirdas Peritoneal Dialysis in Acute Renal Failure -- Why the Bad Outcome? N. Engl. J. Med., September 19, 2002; 347(12): 933 - 935. [Full Text] [PDF]

				H. van Thien, M.T. Ackermans, E. Dekker, V.O. T. Chien, T. Le, E. Endert, P.A. Kager, J.A. Romijn, and H.P. Sauerwein Glucose production and gluconeogenesis in adults with cerebral malaria QJM, December 1, 2001; 94(12): 709 - 715. [Abstract] [Full Text] [PDF]

				S. Krishna, N. V. Nagaraja, T. Planche, T. Agbenyega, G. Bedo-Addo, D. Ansong, A. Owusu-Ofori, A. L. Shroads, G. Henderson, A. Hutson, et al. Population Pharmacokinetics of Intramuscular Quinine in Children with Severe Malaria Antimicrob. Agents Chemother., June 1, 2001; 45(6): 1803 - 1809. [Abstract] [Full Text] [PDF]

				S. Krishna, T. Planche, T. Agbenyega, C. Woodrow, D. Agranoff, G. Bedu-Addo, A. K. Owusu-Ofori, J. A. Appiah, S. Ramanathan, S. M. Mansor, et al. Bioavailability and Preliminary Clinical Efficacy of Intrarectal Artesunate in Ghanaian Children with Moderate Malaria Antimicrob. Agents Chemother., February 1, 2001; 45(2): 509 - 516. [Abstract] [Full Text] [PDF]