title: Glucose homeostasis in children with falciparum malaria: precursor supply limits gluconeogenesis and glucose production.
abstract: To evaluate glucose kinetics in children with falciparum malaria, basal glucose production and gluconeogenesis and an estimate of the flux of the gluconeogenic precursors were measured in Kenyan children with uncomplicated falciparum malaria before (n = 11) and during infusion of alanine (1.5 mg/kg.min; n = 6). Glucose production was measured by [6,6-2H2]glucose, gluconeogenesis by mass isotopomer distribution analysis of glucose labeled by [2-13C]glycerol. Basal plasma glucose concentration ranged from 2.1-5.5 mmol/L, and basal glucose production ranged from 3.3-7.3 mg/kg.min. Glucose production was largely derived from gluconeogenesis (73 +/- 4%; range, 52-93%). During alanine infusion, plasma glucose increased by 0.4 mmol/L (P = 0.03), glucose production increased by 0.8 mg/kg.min (P = 0.02), and gluconeogenesis increased by 0.8 mg/kg.min (P = 0.04). We conclude that glucose production in children with uncomplicated falciparum malaria is largely dependent on gluconeogenesis. However, gluconeogenesis is potentially limited by insufficient precursor supply. These data indicate that in children with falciparum malaria, gluconeogenesis fails to compensate in the presence of decreased glycogen flux to glucose, increasing the risk of hypoglycemia.
authors.affiliation: Department of Internal Medicine, University of Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Dekker
authors.forename: M K
authors.initials: MK
authors.lastname: Hellerstein
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: R A
authors.initials: RA
authors.lastname: Neese
authors.forename: N
authors.initials: N
authors.lastname: Peshu
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: K
authors.initials: K
authors.lastname: Marsh
authors.forename: H P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D003903:Deuterium; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis*; D005990:Glycerol / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007630:Kenya; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood*; D008297:Male
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D019344:Lactic Acid; D003903:Deuterium; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone