Glycogenolysis during short-term fasting in malaria and healthy subjects—the potential regulatory role of glycogen content on glycogen breakdown: a hypothesis

Abstract

Background & aims: 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. Methods: In six non-severe falciparum malaria patients and 6 healthy controls glucose production with [6,6- 2H 2]-glucose, and glycogenolysis was calculated after measuring gluconeogenesis with the 2H 2O-method between 16 and 22 h of fasting. Results: 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 μmol/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. Conclusion: 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.