title: Mechanisms behind decreased endogenous glucose production in malnourished children.
abstract: Severe malnutrition is a major health problem in developing countries and can present itself as kwashiorkor or marasmus. Although marasmus is characterized by clinical wasting, kwashiorkor is associated with peripheral edema, oxidative stress, hypoalbuminemia, and hypoglycemia. The etiology of the hypoglycemia is poorly understood. We determined endogenous glucose production (EGP) in children with severe malnutrition. Children with kwashiorkor, marasmus, and controls received a primed constant infusion of [6,6H2]glucose for 2 h. An i.v. bolus of 13C-ketoisocaproic acid (KIC) was given, and breath samples were obtained during 2 h. Isotope dilution was used to calculate EGP, and 13CO2/12CO2 production was determined. Mean EGP ± SEM was 5.5 ± 0.3 mg/kg/min in the kwashiorkor group and 6.9 ± 0.4 mg/kg/min and 7.6 ± 0.7 mg/kg/min in the marasmic and control group, respectively, (p < 0.05 kwashiorkor versus marasmus and controls). EGP correlated with serum albumin concentration (r = 0.67; p < 0.001) and urinary 8-hydroxydeoxyguanosine as a marker of oxidative stress (r = -0.62; p < 0.005). 13CO2 secretion as a marker of hepatic mitochondrial function was significantly higher in the marasmic group compared with kwashiorkor and controls. We conclude that decreased EGP in severely malnourished children is related to the degree of hypoalbuminemia and oxidative stress but is not associated with a clear defect in hepatic mitochondrial function.
authors.affiliation: Department of Biochemistry, University of Malawi, Blantyre 360, Malawi. robert.bandsma@sickkids.ca
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Bandsma
authors.forename: Marijke
authors.initials: M
authors.lastname: Mendel
authors.forename: Martijn N
authors.initials: MN
authors.lastname: Spoelstra
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Reijngoud
authors.forename: Theo
authors.initials: T
authors.lastname: Boer
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.forename: Bernard
authors.initials: B
authors.lastname: Brabin
authors.forename: Reijnout
authors.initials: R
authors.lastname: Schellekens
authors.forename: Edward
authors.initials: E
authors.lastname: Senga
authors.forename: Geert Tom
authors.initials: GT
authors.lastname: Heikens
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D015362:Child Nutrition Disorders / Q000378:metabolism*; D003906:Developing Countries; D005934:Glucagon / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D034141:Hypoalbuminemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007732:Kwashiorkor / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D018384:Oxidative Stress; D011502:Protein-Energy Malnutrition / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012709:Serum Albumin; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone