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, im plying insulin resistance. If the infection progresses, the risk of hy poglycemia will increase as host glucose production becomes insufficie nt for host/parasite demand. To assess the relative contribution of in sulin-mediated and non-insulin-mediated glucose disposal to plasma glu cose levels in severe malaria, we studied six healthy controls (two ma les and four females; mean age, 38 years) and eight patients with comp licated falciparum malaria (five males and three females; mean age, 31 years) who had a frequently sampled intravenous glucose tolerance tes t (FSIVGTT) in which 10% of the dextrose bolus was 6,6-D-2-glucose. Th e minimal model was applied to native and labeled plasma glucose and s erum 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 lo wer 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 mu U/mL in controls, P = .026). Glucose effectiveness ([SG] the ability of glucose to reduce its own p lasma 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 dis appearance at basal concentration was increased by a median of 42% in severe malaria patients, with the insulin-independent component compri sing 81%, versus 67% in controls. Indices of beta-cell function were n ormal in malaria patients. These data demonstrate that basal plasma gl ucose utilization is increased approximately 50% in severe malaria, co nsistent with previously published isotope-turnover studies. Altered S G plays a major role. Prevention and treatment of early hypoglycemia s hould be based on adequate glucose replacement. Strategies that reduce insulin secretion or effects appear to be of minor importance. Copyri ght (C) 1997 by W.B. Saunders Company.