Glucose metabolism in severe malaria: Minimal model analysis of the intravenous glucose tolerance test incorporating a stable glucose label

Basal plasma glucose is usually increased in uncomplicated malaria, implying insulin resistance. If the infection progress, the risk of hypoglycemia will increase as host glucose production becomes insufficient for host/parasite demand. To assess the relative contribution of insulin- mediated and non-insulin-mediated glucose disposal to plasma glucose levels in severe malaria, we studied six healthy controls (two males and four females; mean age, 38 years) and eight patients with complicated falciparum malaria (five males and three females; mean age, 31 years) who had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in which 10% of the dextrose bolus was 6,6-D2-glucose. The minimal model was applied to native and labeled plasma glucose and serum insulin profiles over 4 hours postinjection. Basal plasma glucose concentrations in the patients were significantly greater than in the controls (median [range], 6.1 [2.1 to 8.5] v 4.3 [3.9 to 4.7] mmol/L, P = .03). Malaria-associated insulin resistance was confirmed by a lower insulin sensitivity index (SI) in patients (5.6 [2.4 to 17.4] v 16.0 [2.5 to 22.3] x 10-4 · min-1 per μU/mL in controls, P = .026). Glucose effectiveness ([SG] the ability of glucose to reduce its own plasma concentration) was higher in the patients (0.015 [0.006 to 0.024] v 0.008 [0.007 to 0.010] min-1 in controls, P = .019). Glucose disappearance at basal concentration was increased by a median of 42% in severe malaria patients, with the insulin-independent component comprising 81%, versus 67% in controls. Indices of β-cell function were normal in malaria patients. These data demonstrate that basal plasma glucose utilization is increased approximately 50% in severe malaria, consistent with previously published isotope-turnover studies. Altered SG plays a major role. Prevention and treatment of early hypoglycemia should be based on adequate glucose replacement. Strategies that reduce insulin secretion or effects appear to be of minor importance.