glycogen and Malaria--Falciparum

In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased. To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated falciparum malaria, we investigated the effect of inhibition of lipolysis by acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were given acipimox, and six served as controls. Also as controls, six matched healthy subjects were studied on two occasions with and without acipimox. After 16 h of fasting, glucose production and GNG were significantly higher in the malaria patients compared with the healthy controls (P = 0.003 and < 0.0001, respectively), whereas GLY was significantly lower (P < 0.001), together with elevated plasma concentrations of cortisol and glucagon. During the study, glucose production in patients declined over time (P < 0.0001), without a statistically significant difference between the acipimox-treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared with nontreated controls (P = 0.005). GNG was unchanged over time in patients as well as in healthy controls, and no influence of acipimox was found. In patients, GLY declined over time (P < 0.001), without a difference between acipimox-treated and untreated patients. In contrast, in controls treated with acipimox, no change over time was found, which was statistically different from the decline in untreated controls (P = 0.002). In conclusion, in falciparum malaria, FFAs are not involved in regulation of glucose production, nor of GNG or GLY.

Topics: Adult; Alanine; Fatty Acids, Nonesterified; Female; Gluconeogenesis; Glucose; Glycogen; Humans; Hypolipidemic Agents; Insulin; Interleukin-10; Lactic Acid; Malaria, Falciparum; Male; Pyrazines; Tumor Necrosis Factor-alpha

During short-term starvation (< 24 h), glucose production decreases 10-20% due to a decrease in glycogenolysis. In the fed state glycogen regulates its rate of breakdown, in order to limit glycogen accumulation. Whether in the fasted state a similar mechanism exists to preserve glycogen content is not known. In malaria, the rate of glycogen breakdown after an overnight fast is considerably lower than in healthy subjects. If glycogen content regulates its rate of breakdown during fasting, we postulate that the rate of glycogenolysis should decrease faster in patients with malaria than in healthy subjects.. In six non-severe falciparum malaria patients and 6 healthy controls glucose production with [6,6-2H2]-glucose, and glycogenolysis was calculated after measuring gluconeogenesis with the 2H2O-method between 16 and 22 h of fasting.. Glucose production after 16 h of fasting was 15% higher in the malaria patients than in controls. Glycogenolysis in the malaria patients was 2.3 +/- 0.37 and 8.4 +/- 0.93 micromol/kg/min in the controls. The absolute decrease in glycogenolysis was slower in malaria patients than in controls (P = 0.001), whereas the relative decrease in glycogenolysis from baseline was not different.. During fasting the relative decrease in glycogenolysis is independent of the absolute rate of glycogenolysis. The regulation of glycogenolysis during fasting seems not preferentially dictated by glycogen content but, at least in subjects with a low (presumed) glycogen content, driven by the necessity to guarantee glucose output and maintain euglycemia.

Topics: Adult; Blood Glucose; Deuterium; Fasting; Female; Gluconeogenesis; Glycogen; Humans; Malaria, Falciparum; Male; Time Factors

Although glucose production is increased in severe malaria, the influence of uncomplicated malaria on glucose production is unknown. Therefore, we measured in eight adult Vietnamese patients with uncomplicated falciparum malaria and eight healthy Vietnamese controls glucose production (by infusion of [6,6-2H2]glucose) and the fractional contribution of gluconeogenesis (by oral ingestion of 2H2O); glycogenolysis was calculated as the difference between the two. After 20 h of fasting, plasma glucose was 4.7 +/- 0.2 mmol/l in the patients and 4.3 +/- 0.2 mmol/l in the controls (not significant). Glucose production was approximately 25% higher in the patients (16.9 +/- 1.3 vs. 13.4 +/- 0.3 mumol.kg-1.min-1, P = 0.01). Fractional and absolute gluconeogenesis were increased in the patients (approximately 87 vs. approximately 59%, P < 0.001; and 14.6 +/- 1.3 vs. 7.9 +/- 0.2 mumol.kg-1.min-1, P < 0.001, respectively). The contribution of glycogenolysis to total glucose production was decreased in the patients: 2.3 +/- 0.5 vs. 5.5 +/- 0.4 mumol.kg-1.min-1 (P < 0.002). In conclusion, in adult patients with uncomplicated falciparum malaria, glucose production is increased by approximately 25% due to an increased rate of gluconeogenesis, whereas glycogenolysis is decreased. The mechanism by which these changes occur is uncertain. However, counterregulatory hormone and cytokine concentrations were increased in the patients.

Topics: Adult; Alanine; Deuterium; Epinephrine; Glucagon; Gluconeogenesis; Glucose; Glycerol; Glycogen; Humans; Hydrocortisone; Insulin; Lactates; Malaria, Falciparum; Male; Norepinephrine; Radioisotope Dilution Technique; Reference Values; Vietnam