Glucose loading test

Investigation of the redox status in plasma on the basis of the molar L/P and B/A ratios in vivo can help to discriminate between several causes of congenital lactic acidosis. An intravenous glucose loading test (GTT 2 g/kg b.w.) might be advantageous to get more information about the redox status. An increased L/P ratio and a normal or decreased B/A ratio would be suggestive for a defect in the citric acid cycle. 

Urine for amino acid and organic acid analysis should be collected in the fed state. If no lactate increase is found in body fluids, an oral glucose loading test should be performed (see Sect. 27.7). 

A standardized oral glucose loading test, with 2 g glucose/kg body weight, and blood sampling at 0, 30, 60, 90, 120 and 180 min after intake, provides insight into the capacity for in vivo pyruvate oxidation. Pyruvate oxidation may be impaired if the peak increase in blood lactate surpasses 1 mmol/1 or double the value of the basal concentration. It is unclear whether the liver mitochondria are more involved in this test than the muscle mitochondria. Even normal test results do not totally exclude mitochondrial dysfunctioning. 

The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. 

For special purposes the effect of blood glucose lowering agents is studied in glucose loaded animals. Rabbits of either sex weighing 3.0-4.5 kg are treated either once (0.5 h after test compound) or twice (0.5 and 2.5 hours after test compound) orally with 2 g glucose/kg body weight in 50 % solution. 

Fig. 3. Representative oral glucose tolerance test shown for a candidate compound, which impairs glucose tolerance. Candidate compound and vehicle are administered 2 hours before the oral glucose load. Values are mean +/- SEM, n = 8 rats...

After the in vitro characterization, the system was tested in vivo in rabbits and in humans the first unexpected, and not previously noted, problem was a sharp decrease in the sensitivity after about 1 h following both an intravenous (in the rabbit) and an oral (in the human) glucose load. 

Interpretation Serum GH concentrations in normal individuals fall to <2 ng/mL subjects with acromegaly fail to show this suppression and sometimes show a paradoxical increase in GH concentration. Patients with liver disease, uremia, or heroin addiction may have false-positive results with this test (failure to suppress serum GH concentrations after oral glucose load). 

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