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Glucose homeostasis in children with falciparum malaria: precursor supply limits gluconeogenesis and glucose
E Dekker1, M K Hellerstein, J A Romijn
1Department of Internal Medicine, University of Amsterdam, The Netherlands.
Insights
In children with falciparum malaria, glucose production heavily relies on gluconeogenesis. Insufficient precursor supply may limit this process, increasing hypoglycemia risk.
Area of Science:
- Pediatrics
- Infectious Diseases
- Metabolic Research
Background:
- Falciparum malaria is a significant cause of childhood illness.
- Hypoglycemia is a serious complication of malaria in children.
- Glucose metabolism alterations are implicated in malaria-associated hypoglycemia.
Purpose of the Study:
- To investigate glucose kinetics in children with uncomplicated falciparum malaria.
- To determine the contribution of gluconeogenesis to glucose production.
- To assess the impact of precursor availability on gluconeogenesis.
Main Methods:
- Utilized stable isotope tracers ([6,6-2H2]glucose and [2-13C]glycerol) for measuring glucose production and gluconeogenesis.
- Employed mass isotopomer distribution analysis to quantify gluconeogenesis.
- Administered alanine infusion to assess precursor supply effects.
Main Results:
- Basal glucose production was primarily gluconeogenic (73% +/- 4%).
- Alanine infusion increased plasma glucose, glucose production, and gluconeogenesis.
- Gluconeogenesis showed potential limitations due to insufficient precursor supply.
Conclusions:
- Glucose production in children with falciparum malaria is predominantly gluconeogenic.
- Gluconeogenesis may be limited by precursor availability, failing to compensate for decreased glycogenolysis.
- This metabolic dysfunction increases the risk of hypoglycemia in children with falciparum malaria.
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.