Extended metabolic evaluation of suspected symptomatic hypoglycemia: the prolonged fast and beyond

The diagnostic evaluation of spontaneous hypoglycemia in adults is mainly directed at detecting an insulinoma. Its interpretation is troublesome in those patients who develop low venous plasma glucose levels with appropriate hypoinsulinemia during a prolonged supervised fast. In this study, we investigated in this group of patients whether abnormalities in intermediary metabolism (fatty acid oxidation and amino/organic acids) could be detected that might explain the hypoinsulinemic hypoglycemia. Ten patients with otherwise unexplained low venous plasma glucose levels (<3 mmol/L) during prolonged fasting were included in the study. The patients participated in an extended metabolic protocol based on stable isotope techniques after an overnight fast to explore abnormalities in endogenous glucose production and intermediary metabolism. Endogenous glucose production, glucoregulatory hormones, plasma acylcarnitines, gluconeogenic amino acids, and rates of fatty acid and carbohydrate oxidation after 16 and 22 hours of fasting were measured. Although during the prolonged fast all patients had low venous plasma glucose level, there were no hypoglycemic events during the extended metabolic protocol. No abnormalities in endogenous glucose production (compared with reference values obtained in young healthy volunteers), fatty acid oxidation, or amino acid/organic acids were found in this patient group. In a group of patients exhibiting low venous plasma glucose levels during prolonged fasting in whom insulinoma was excluded, we found no signs of metabolic disorders. Therefore, the observation of low plasma glucose values in this subgroup of patients probably does not warrant extensive metabolic evaluation.