Failure to suppress C-peptide secretion by euglycaemic hyperinsulinaemia: a new diagnostic test for insulinoma?

In order to study the suppression of C-peptide secretion in 5 patients with insulin-producing tumours or beta cell hyperplasia, we raised and maintained plasma insulin at a high physiological level and kept plasma glucose unchanged for 2 h with combined infusions of glucose and insulin (insulin clamp technique). No suppression of C-peptide secretion was seen in any of the patients, in contrast with a 35-65% decline seen in each of 17 healthy control subjects. In 3 patients surgical removal of beta cell adenoma normalized the response, whereas it remained unchanged in a patient with beta cell hyperplasia after partial pancreatectomy and in another with inoperable carcinoma. These results indicate that insulin secretion by insulinomas is characterized by lack of suppression by insulin. Measurement of the insulin-insulin feedback loop by the clamp technique may provide a rapid test to reveal autonomous insulin secretion without the risk of hypoglycaemia.