Metabolism
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A hypoglycaemic adolescent with an enlarged liver and gout
AP is a 16 year old boy. As an infant he was liable to convulsions if he was not fed at regular intervals. He has a greatly enlarged liver, which is readily palpable. For the last year he has suffered increasingly from gout, with deposition of crystals of uric acid in joints.
The following results were obtained on blood samples taken after an overnight fast:
glucose (mmol /L) |
insulin (mU /mL) |
non-esterified fatty acids (mmol /L) |
|
| AP | 2.2 |
2.0 |
2.08 |
| 10 age-matched control subjects | 4.0 ± 0.16 |
9 ± 0.7 |
0.71 ± 0.08 |
What conclusions can you draw from these results?
He has very low plasma glucose in the fasting state. Indeed, this is close to the level at which we might expect to see disturbance of consciousness or convulsions.
His plasma insulin is very low, presumably as a result of the low circulating concentration of glucose. It is unlikely that his problem is failure to secrete insulin (i.e. diabetes mellitus), since in this case we would expect to see a high plasma concentration of glucose with low insulin.
His plasma free fatty acids are very high in the fasting state. This would be expected from the low plasma glucose, since fatty acids will be mobilised from adipose tissue to provide an alternative fuel. We are not given any data, but we would expect his plasma ketone bodies (acetoacetate and hydroxybutyrate) to be high as well.
Although neither the enlarged liver nor the hypoglycaemia with low plasma insulin is typical of diabetes mellitus, in order to be sure he was given an oral dose of 1 g of glucose /kg body weight, and his plasma glucose was measured over 4 hours afterwards - a standard oral glucose tolerance test.
What conclusions can you draw from the results of the glucose tolerance test?
The response to a 50g test dose of glucose clearly eliminates the possibility of diabetes mellitus; in diabetes we would expect to see a very much greater than normal rise in plasma glucose, to considerably above 10 mmol/L, remaining high for much longer. Certainly we would not expect to see the sharp fall in plasma glucose 3½ - 4 h after the test dose. The patient is able to maintain plasma glucose near the normal range after the test dose, so there is no impairment of his ability to take up glucose into tissues, either for oxidation as a metabolic fuel or for glycogen synthesis.
50g of glucose yields 800 kJ; the average energy expenditure of a 16y old boy is 9 - 9.5 MJ/day; allowing for his initially high plasma free fatty acids, it is to be expected that by 3½ - 4 hours after 50g of glucose he would again be in a fasting state.
What is abnormal is that his plasma glucose again falls to a very low level. You would normally expect plasma glucose to be maintained within the normal range by utilisation of the liver glycogen that has been synthesised in response to the glucose load.
A liver biopsy was taken from AP after an overnight fast, and from a control subject of the same age who was being investigated for an unrelated condition. The dark granules in the electron micrographs below are glycogen granules.
