Efficacy of insulin and C-peptide suppression test using a rapid-acting insulin analog to induce hypoglycemia in the diagnosis of insulinoma: A comparison to the supervised prolonged fast test

Abstract

BackgroundThe efficacy of insulin and C-peptide suppression (ICPS) test using a rapid-acting insulin analog to induce hypoglycemia in the diagnosis of insulinoma has never been studied. ObjectiveTo compare the efficacy of using plasma C-peptide (PCP) and plasma insulin (PI) responses to the ICPS test using insulin aspart and the supervised prolonged fast (SPF) test in the diagnosis of insulinoma. MethodsThe ICPS test was performed in 15 patients with insulinoma (IN) and 6 patients with non-insulinoma causes of hypoglycemia (non-IN) by intravenous infusion of insulin aspart to induce hypoglycemia. Plasma glucose (PG), C-peptide (PCP), and insulin (PI) levels were measured before and at the end of the test (end-ICPS) when the patients had hypoglycemia, defined by the presence of either PG ≤50 mg/dL with hypoglycemic symptoms or PG ≤40 mg/dL regardless of hypoglycemic symptoms. PCP and PI were measured by an immunoassay system that does not cross-react to insulin aspart (Cobas Modular Analytics e801). The SPF test was also performed in IN. ResultsIN had a higher median end-ICPS PI (34.77 versus 0.58 μIU/mL, p < 0.001), lower magnitude of PI suppression (−24.28 % ± 35.5 % versus −93.67 % ± 2.7 %, p < 0.001), higher mean end-ICPS PCP (4.62 ± 3.02 versus 0.49 ± 0.21 ng/mL, p < 0.001), and lower magnitude of PCP suppression (−25.51 % ± 22.2 % versus −70.28 % ± 19.4 %, p < 0.001) than non-IN. In IN, end-ICPS PI was significantly correlated to end-ICPS PCP (r = 0.724, p = 0.002). There were high correlations between end-ICPS PCP and end-SPF PCP (r = 0.882, p < 0.001) and between end-ICPS PI and end-SPF PI (r = 0.794, p < 0.001). The ICPS had a sensitivity and specificity of 93 % and 83 %, respectively, when using an end-ICPS PCP cut-off level of 0.6 ng/mL and 93 % and 100 %, respectively, when using an end-ICPS PI cut-off level of 3 μIU/mL. The ICPS test was terminated in a shorter time than the SPF test (1.01 ± 0.58 versus 7.80 ± 4.10 h, p < 0.001). ConclusionIn the diagnosis of insulinoma, the ICPS test using insulin aspart is practical, safe, less time-consuming, and as effective as the SPF test. The responses of PI to hypoglycemia are more obvious and consistent, without overlap, than the responses of PCP in IN and non-IN. The use of end-ICPS PI is better than end-ICPS PCP in the evaluation of the ICPS test. The ICPS test using a rapid-acting insulin analogue such as insulin aspart can be used instead of the conventional CPS test using recombinant human insulin and should be considered an alternative first-line test to the SPF test.