Carbohydrate metabolism in phenylketonuria

Carbohydrate metabolism was studied in 6 adult patients with phenylketonuria both on a low phenylalanine and an unrestricted institutional diet. Tolerance tests included PO glucose, PO phenylalanine, and combined glucose and phenylalanine loading. Glucose, insulin, pyruvate, lactate, and phenylalanine were sampled at 0, ½, 1, 2, 3, and 4 hr. Fasting glucose levels were normal as were mean glucose values after challenge. Basal insulin secretion, as well as insulin response, to glucose challenge and to combined phenylalanine and glucose loading appeared normal. Insulin response to phenylalanine alone, however, was lower than expected in the phenylketonuria patients. Both off and on low phenylalanine diet, blood pyruvate and lactate values were also normal. Thus, our data from blood did not show evidence of the abnormalities in glucose and pyruvate metabolism which have been proposed to occur in phenylketonuric patients but did suggest that the potency of phenylalanine as an insulin secretagogue is diminished by chronic hyperphenylalaninemia. Speculation: Carbohydrate metabolism following a glucose load and measured in whole blood appears normal in phenylketonuria. In contrast, the insulin response to a phenylalanine load appears decreased. Chronic hyperphenylalaninemia may produce a state of subsensitivity of the pancreas for the insulin response to an acute phenylalanine load.