c-peptide and Malaria

Glycaemic status on hospital admission was compared in 97 children with severe falciparum malaria (36 with cerebral malaria) and 89 children with other serious illnesses (32 in coma; 57 with acute pneumonia, not in coma). The frequency of hypoglycaemia (blood glucose below 2.2 mmol/l) did not differ significantly between malarial and control patients (5.2% vs 11.2%) nor between the comatose (11.1% vs 18.8%) and conscious (1.6% vs 7.0%) malarial and control subgroups. Compared with normoglycaemic patients, hypoglycaemic patients had appropriately low serum insulin (3.0 vs 8.2 mU/l) and C-peptide (0.13 vs 0.42 mmol/l) and high plasma non-esterified fatty acids (1.42 vs 0.83 mmol/l). Hypoglycaemia, the level of consciousness, and death were all significantly associated with the time since the last meal. Hypoglycaemia is not a specific complication of malaria but is found in severely ill fasted children, resulting from glycogen depletion and perhaps impaired hepatic gluconeogenesis. It should be sought in all severely sick children. A single bolus dose of glucose may not be enough to correct it.

Topics: Alanine; Blood Glucose; Brain Diseases; C-Peptide; Child; Child, Preschool; Coma; Discriminant Analysis; Eating; Evaluation Studies as Topic; Fatty Acids, Nonesterified; Glasgow Coma Scale; Humans; Hypoglycemia; Infant; Infant, Newborn; Insulin; Malaria; Prognosis; Time Factors

To investigate host and drug effects on glucose metabolism in acute falciparum malaria, 10 previously untreated, fasting Thai males with uncomplicated infections were given a 2-h intravenous glucose infusion (5 mg/kg ideal body weight min) with an infusion of quinine dihydrochloride (10 mg/kg body weight) during the second hour. Eight patients were restudied in convalescence. Fasting plasma glucose (mean +/- SD) and insulin (geometric mean (-SD to + SD] were higher during acute illness (5.5 +/- 1.0 mmol/l and 6.2 (5.0-7.7) mU/l) than in convalescence (4.2 +/- 0.25 mmol/l and 3.7 (2.1-6.7) mU/l; P less than 0.001 and P = 0.058 respectively). After 1 h, both plasma glucose (9.3 +/- 1.4 vs 7.5 +/- 0.8 mmol/l, P less than 0.001) and insulin (21.2 (13.8-32.5) vs 15.2 (11.2-20.8) mU/l, P = 0.089) remained higher during acute illness; mathematical model (CIGMA) assessment of these values indicated lower tissue insulin sensitivity on admission (97% (71-134] than in convalescence (139% (109-178), P less than 0.025) but normal beta-cell function on both occasions. Two-hour plasma glucose (9.5 +/- 2.0 mmol/l) and insulin (81.8 (51.5-129.9) mU/l) concentrations during acute illness were also significantly higher than in convalescence (7.2 +/- 1.2 mmol/l and 40.1 (23.5-68.4) mU/l, P less than or equal to 0.025) despite similar end-infusion free plasma quinine concentrations (P greater than 0.5). Basal plasma free fatty acid concentrations were increased in acute illness (0.68 +/- 0.24 vs 0.21 +/- 0.12 mmol/l, P less than 0.001) but fell to low levels at 2 h in both studies. These data suggest tissue insulin resistance and augmented quinine-stimulated insulin secretion in acute falciparum malaria, factors which are likely to influence the clinical situation in which malaria-associated hypoglycaemia occurs.

Topics: Acute Disease; Adolescent; Adult; Animals; Blood Glucose; C-Peptide; Fasting; Fatty Acids, Nonesterified; Glucose Clamp Technique; Homeostasis; Humans; Insulin; Insulin Resistance; Malaria; Male; Middle Aged; Plasmodium falciparum; Quinine

We studied the occurrence, clinical manifestations, and mechanism of hypoglycemia in patients with falciparum malaria in eastern Thailand. Hypoglycemia, which was often severe and recurrent, occurred in 17 patients, including 12 in a series of 151 patients with cerebral malaria. Thirty episodes were investigated. Plasma concentrations of insulin and C peptide were inappropriately high, and lactate and alanine concentrations were significantly higher than in patients with falciparum malaria who were normoglycemic (P less than 0.05). Sixteen patients had received quinine; plasma quinine and insulin concentrations were correlated at the time of hypoglycemia (P = 0.007). In seven healthy fasting volunteers intravenous quinine increased the mean plasma insulin concentration (+/- S.D.) from 8.9 +/- 3.1 to 17.1 +/- 8.4 mU per liter (P = 0.02) and reduced the mean plasma glucose concentration from 88 +/- 20 to 68 +/- 23 mg per deciliter (P = 0.002). Our observations indicate that in falciparum malaria quinine-induced insulin secretion may precipitate hypoglycemia, but other factors, including the large glucose requirements of the malaria parasites may also contribute. This important complication, associated with pregnancy and severe disease, must be excluded in all patients with falciparum malaria who have impaired or deteriorating consciousness.

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Alanine; Blood Glucose; Brain Diseases; C-Peptide; Child; Female; Humans; Hydroxybutyrates; Hypoglycemia; Insulin; Lactates; Lactic Acid; Malaria; Male; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Infectious; Quinine