A severe but reversible reduction in insulin sensitivity is observed in patients with insulinoma

Hypoglycemic manifestations are highly variable in patients with an insulinoma and largely independent of tumour size and severity of insulin hypersecretion.

We investigated the clinical, biological and tumoral characteristics of insulinomas in a large monocentric series of patients and we evaluated their insulin sensitivity before and after successful pancreatic surgery.

This was a retrospective analysis of 40 patients treated for an insulinoma between 1982 and 2012 in our academic hospital. Insulin sensitivity and beta cell function were evaluated by a HOMA test outside hypoglycaemic episodes in a large subset of these patients.

The mean age at onset of symptoms was 48.8±20.1 years and the mean age at diagnosis was 50.7±19.9 years. Neuroglycopenic symptoms were observed in 90% of patients. The most effective preoperative imaging technique to localize the tumour was endoscopic ultrasound. Insulin sensitivity was greatly reduced in patients with insulinoma (38.9%±22.3%), while beta cells function was increased (359.0±171.5%), but to a variable extent (range: 110.6-678.6%). After complete resection of the tumour and remission of hypoglycemic episodes, insulin sensitivity increased in all evaluated subjects (72.8±36.7%) and normalized in the majority.

Although neuroglycopenic symptoms are present in most patients, diagnosis of insulinoma is often delayed. Endoscopic ultrasound remains the most sensitive preoperative technique to localize the tumour. We also show that in response to chronic hyperinsulinemia, patients with insulinoma develop protective mechanisms responsible for a marked insulin resistance, which is reversible after complete resection of the tumour.