Influence of prolonged starvation on glucose kinetics in pregnant patients infected with Plasmodium falciparum

Hypoglycaemia is a recognised complication of malaria in pregnancy, but its pathophysiology is not well understood. We studied the influence of fasting on glucose production and gluconeogenesis by infusion of [6,6-2H2]glucose and ingestion of 2H2O in 20 female subjects, eight pregnant patients with uncomplicated falciparum malaria, six pregnant controls matched for age and trimester and six non-pregnant controls matched for age. Infection with Plasmodium falciparum induced a significant increase in glucose production (16.7±0.3 vs. 12.4±0.8 μmol/kg/min; P=0.002) and gluconeogenesis (12.5±0.6 vs. 8.2±0.7 μmol/kg/min; P=0.001) without a change in the glucoregulatory hormone milieu, compared to the healthy pregnant controls. Extension of the fast from 20.30 to 24.30 h resulted in a rate of decline of glucose production that was similar in patients with malaria and healthy pregnant subjects, a decline that was steeper compared to the non-pregnant subjects (−0.283 and −0.426 vs. −0.065 μmol/kg/min/h; P=0.037). The plasma glucose concentration measured at 20.30 h of fasting in the malaria patients was intermediate between the value found in the pregnant and the non-pregnant controls (4.01±0.2 mmol/l) while it was significantly lower in the non-infected pregnant women compared to non-pregnant controls (3.59±0.14 vs. 4.70±0.29 mmol/l; P=0.009). Plasma glucose concentration declined at a similar rate in patients with malaria and pregnant controls but faster compared to the non-pregnant controls (−0.078 and −0.093 vs. −0.044 mmol/l/h; P < 0.05). We conclude that fasting is a major risk factor for hypoglycaemia in pregnancy. Non-severe Plasmodium falciparum infection in pregnant women results in higher glucose production and higher glucose levels, thereby, compared to healthy pregnant patients, delaying of the occurrence of hypoglycaemia due to fasting. The exact mechanism of hypoglycaemia in fasting pregnant women remains to be elucidated.