Glycerol metabolism in severe falciparum malaria

Gluconeogenesis and liver blood flow (LBF) in severe falciparum malaria were assessed from the clearance and metabolic response to intravenously administered glycerol (0.3 g/kg) and Indocyanine Green ([ICG] 0.4 mg/kg), respectively. Fasting baseline blood glycerol concentrations (mean ± SD) were significantly higher in acute malaria (133 ± 65 μmol/L, n = 14), than in convalescence (65 ± 31 μmol/L, n = 9, P = .01), but basal triacylglycerol concentrations were similar. Estimated glycerol turnover was also more than twice as high in acute malaria compared with convalescence (1.36 ± 0.87 v 0.54 ± 0.15 μmol · min−1 · kg−1, P = .015). The increment in plasma glucose (AUC0–55 min) following glycerol infusion was greater during acute malaria compared with convalescence (median [range], +31.6 [−0.9 to + 107.6] v + 14.5 [−103 to +27.1] mmol · min · L−1, P < .05), but the insulin increments were similar (P = .9), indicating reduced tissue insulin sensitivity. The increment in venous lactate (AUC0–55 min) was higher in severely ill patients (17.2 [−7.8 to +53.4] mmol · min · L−1, n = 10) compared with patients with moderately severe malaria (−3.1 [−8.7 to 3.2] mmol · min · L−1, n = 4, P = .01). LBF estimated from ICG clearance was lower during acute illness than in convalescence (mean ± SD, 15.5 ± 2.3 v 18.6 ± 2.9 mL · min−1 · kg−1, P = .007) and correlated inversely with the basal venous lactate concentration (r s = .53, P < .05). LBFs less than 15 mL · min−1 · kg−1 were associated with hyperlactatemia, and all four fatal cases had LBFs of less than 12 mL · min−1 · kg−1. Thus, despite the propensity to hypoglycemia in severe falciparum malaria, the clearance and metabolic responses to glycerol were relatively unaffected. These data also provide evidence of increased glycolysis and an association between reduced LBF and lactic acidosis in severe malaria.