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Hypoglycaemia on and after admission in Kenyan children with severe malaria
Insights
Hypoglycaemia in severe childhood malaria is not caused by a lack of gluconeogenic substrates like glycerol. Impaired gluconeogenesis, not substrate limitation, is the likely cause, and glucose monitors may be inaccurate.
Area of Science:
- Pediatrics
- Infectious Diseases
- Biochemistry
Background:
- Severe malaria in African children frequently causes hypoglycaemia (low blood glucose).
- The role of gluconeogenesis (glucose production) and its substrates in this condition is not fully understood.
- Glycerol is a potential substrate for gluconeogenesis, but its contribution to preventing hypoglycaemia in severe malaria is unclear.
Purpose of the Study:
- To investigate the pathophysiology of hypoglycaemia in severe childhood malaria.
- To determine the importance of glycerol as a gluconeogenic substrate.
- To assess whether substrate limitation contributes to hypoglycaemia in severe malaria.
Main Methods:
- Studied 171 African children with moderate or severe malaria.
- Measured blood levels of gluconeogenic precursors (alanine, lactate, glycerol).
- Assessed acid-base status and renal function in hypoglycaemic and non-hypoglycaemic children.
Main Results:
- 16% of children were hypoglycaemic on admission; 9% experienced hypoglycaemia after treatment.
- Blood levels of gluconeogenic precursors were not lower in hypoglycaemic children.
- Hypoglycaemic children showed greater acidosis and renal impairment compared to non-hypoglycaemic children.
- Common blood glucose monitoring devices may overestimate hypoglycaemia frequency.
Conclusions:
- Reduced gluconeogenic substrate supply does not appear to cause hypoglycaemia in severe childhood malaria.
- Impaired gluconeogenesis is a more likely factor in the development of hypoglycaemia.
- Blood glucose monitoring devices may require careful interpretation in this population.
Abstract:
We investigated the pathophysiology of hypoglycaemia in severe malaria in African children, especially the potential importance of glycerol as a substrate for gluconeogenesis, and whether substrate limitation contributes to hypoglycaemia in severe disease. Of 171 children with moderate or severe malaria, 16% were hypoglycaemic on admission, while at least 9% of children with severe malaria treated with quinine and a concurrent 4% dextrose infusion had a definite episode of hypoglycaemia after admission. Blood levels of gluconeogenic precursors are as high (alanine and lactate) or higher (glycerol) in those with either hypoglycaemia on or after admission as they are in children never having an episode of hypoglycaemia. Among children with severe malaria, however, those having a definite episode of hypoglycaemia at some stage are more acidotic and have greater evidence of renal impairment than those who are never hypoglycaemic (mean base excess -14.4 vs. -7.2, p < 0.001, mean creatinine 97 vs. 64, p < 0.001 and mean urea 8.1 vs. 5.8, p = 0.03, respectively). These data do not support a role for reduced gluconeogenic substrate supply in the pathogenesis of hypoglycaemia in severe childhood malaria, but do support the hypothesis that gluconeogenesis is impaired. Commonly-used bedside blood glucose monitoring devices may overestimate blood glucose measurements in the normal range, and paradoxically may also seriously overestimate the frequency of hypoglycaemia.