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Glucose production rates were measured in six patients with glycogen storage disease type 1 (five type 1A, one type 1B) using a primed continuous infusion of either [3-3H]glucose or [6,6-2H2]glucose. In four patients exogenous glucose was needed to maintain normoglycaemia. At blood glucose concentrations of 2.3-4.7 mmol/L, the endogenous glucose production rates were between 34 and 100% of that predicted for healthy subjects. No relationship was found between the blood glucose concentration and glucose production rates but there was a positive correlation between that of blood lactate and glucose production rate. The initial steady state was perturbed either by reducing the exogenous glucose infusion rate or by giving intravenous glucagon (20 micrograms/kg) or alanine (0.1-0.2 g/kg). Reducing the exogenous glucose infusion rate had little short term effect on glucose production rate. Intravenous glucagon increased the glucose production rate as well as blood glucose and lactate concentrations. A bolus of alanine (0.2 g/kg) given intravenously increased the glucose production rate and blood glucose concentrations but blood lactate concentrations fell. In four of the patients the studies were repeated under similar conditions and the glucose production rate was higher in all patients. We conclude that the glucose production rate is not fixed but varies with the prevailing metabolic status, a finding that has implications for the treatment of type 1 glycogen storage disease.

ABSTRACT. Liver metabolism of two patients (aged 15 and 23 yr) was studied by P-31 magnetic resonance spectroscopy at 1.9 tesla. The P-31 spectra of liver showed the resonances of phosphomonoesters (including sugar phosphates), inorganic phosphate (Pi), phosphodiesters (e.g. glycerophosphorylcholine, glycerophosporylethanolamine), and ATP. These resonances were quantified by expressing their peak areas in mM (assuming that ATP concentrations in normal liver is 2.5 mM) or as a ratio relative to the area of the phosphodiester resonance. After an overnight fast liver phosphomonoesters in patients were 2.6 and 1.6 AU, respectively (controls 1.1 rt 0.5, mean f 2 SD, n = 17). At the same time liver Pi was decreased in patients to 1.3 and 1.0, respectively (controls 1.8 f 0.8). Based on chemical shift measurements the increase in phosphomnnoesters could be attributed to accumulation of sugar phosphates (mainly glycolytic intermediates). After 1 g/kg oral glucose, hepatic sugar phosphates decreased in patients by 64 and 40%, respectively, and reached normal levels (on the absolute intensity scale); whereas liver Pi increased by 130 and 40%, respectively. Liver Pi levels remained elevated in both patients 30 min after ingestion of glucose. Liver sugar phosphates and Pi did not change in control subjects (n = 4) after glucose. In contrast to some previous reports, we have found accumulation of glycolytic intermediates in the liver of glucose-6-phosphatase-deficient patients during fasting. In these patients high levels may enhance the activity of residual glucose-6-phosphatase thus increasing hepatic glucose production and reducing the degree of hypoglycemia during fasting. Hyperuricemia is another serious complication of glucose-6-phosphatase deficiency and was present in both patients. Levels of Pi are known to regulate synthesis and breakdown purines. The changes in liver Pi during fasting and refeeding in these patients may stimulate production of uric acid and contribute to the hyperuricemia. (Pediatr Res 23: 375-380,1988) Glucose-6-phosphatase is necessary for the release of free glucose from glucose-6-P derived from glycogenolysis or gluconeogenesis. The link between glucose-6-phosphatase deficiency and its metabolic manifestations is not clear (1). Fasting hypoglycemia, a typical feature of glucose-6-phosphatase deficiency, can be accounted for by the block in glucose release. However, the striking ability of glucose-6-phosphatase-deficient patients to maintain from 30-100% of the normal glucose output during fasting has been difficult to explain in view of the reduction in hepatic glucose-6-phosphatase activity by more than 95% (2, 3) (Collins JE, Leonard JV, unpublished observations). A second clinical problem in glucose-6-phosphatase-deficient patients is hyperuricemia and gout (4-9). It has been suggested that the block in hepatic glucose release leads to accumulation of glucose-6-P during fasting. Glucose-6-P would overflow into the pentose phosphate shunt, increasing the formation of ribose-5-P and ultima...

Glucose production was measured using stable isotopic techniques in two patients with phosphorylase b kinase deficiency before and after oral ethanol (0.75 g/kg). Glucose production was normal before the ethanol. In one patient, who did not take the full dose of ethanol, glucose production rose initially and then fell. In the other, glucose production fell steadily and in both patients blood lactate concentrations rose. Blood glucose concentrations decreased. Patients with this enzyme deficiency are dependent on the gluconeogenic pathway when fasting and, therefore, ethanol may be potentially hazardous.

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