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 [6,6H 2 ]glucose for 2 h. An i.v. bolus of 13 Cketoisocaproic acid (KIC) was given, and breath samples were obtained during 2 h. Isotope dilution was used to calculate EGP, and 13 CO 2 / 12 CO 2 production was determined. Mean EGP Ϯ SEM was 5.5 Ϯ 0.3 mg/kg/min in the kwashiorkor group and 6.9 Ϯ 0.4 mg/kg/min and 7.6 Ϯ 0.7 mg/kg/min in the marasmic and control group, respectively, (p Ͻ 0.05 kwashiorkor versus marasmus and controls). EGP correlated with serum albumin concentration (r ϭ 0.67; p Ͻ 0.001) and urinary 8-hydroxydeoxyguanosine as a marker of oxidative stress (r ϭ Ϫ0.62; p Ͻ 0.005).13 CO 2 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. (Pediatr Res 68: 423-428, 2010)

Hypoglycemia and Risk Factors for Death in 13 Years of Pediatric Admissions in Mozambique

“…11,13,41 In malnourished patients, glucose homeostasis 41 can be compromised in several ways, including a lack of exogenous nutritional intake, decreased absorption of disaccharides because of intestinal villous atrophy, increased oxidative stress, or glucose uptake compromised by intestinal bacteria. In our series, 62% of all hypoglycemic children were malnourished, with 19.4% being severely malnourished.…”

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

“…increased oxidative stress and hepatic steatosis [12,13]. Furthermore, we recently provided some evidence for a relative decrease in hepatic mitochondrial function in severely malnourished children with signs of metabolic maladaptation [14].…”

“…5C). The strongest decrease was observed with pyruvate plus malate (PM), followed by palmitoyl-CoA plus L-carnitine plus malate (PCM) and succinate 14 plus pyruvate plus malate (SPM). This indicates impaired oxidative phosphorylation (OXPHOS) complex I activity, since dependence of oxygen flux on complex I activity is decreasing in the order PM>PCM>SPM.…”

Malaria-associated hypoglycaemia in children

“…It has been estimated that malnutrition contributes to at least one third of deaths in children <5 years and the presence of hypoglycaemia is potentially a major factor contributing to such a poor prognosis [24]. In these patients, various factors such as lack of exogenous nutritional intake, decreased absorption of disaccharides because of intestinal villous atrophy, increased oxidative stress, or glucose uptake by intestinal bacteria compromise glucose homeostasis [25]. The prognosis in severe malnutrition improves when rigorously applying the WHO management of malnutrition guidelines, which take into special consideration the prevention and early treatment of sepsis and hypoglycaemia [26].…”