Increased blood proinsulin and decreased C-peptide levels in patients with pancreatic cancer.

Background/aims: Abnormal glucose tolerance during oral glucose tolerance test (OGTT) is frequently observed in patients with pancreatic cancer. The abnormality shown in previous studies, however, was characterized mainly by analyses based on immunoreactive insulin or C-peptide response during OGTT, despite their cross-reactivity with proinsulin. The mechanisms responsible for glucose intolerance in patients with pancreatic cancer remain controversial.

Methodology: Both proinsulin and C-peptide responses during 75 g of OGTT were determined without influence of immunologic cross-reactivity in 32 patients with pancreatic cancer and 32 control subjects of similar age, sex, fasting blood glucose levels, and OGTT pattern.

Results: The pancreatic cancer patients had higher proinsulin and lower C-peptide levels than the control subjects both in the non-diabetic and diabetic groups. The ratio of the sum of five proinsulin values observed at 0, 30, 60, 120, and 180 min to that of the five C-peptide values (sigma proinsulin/sigma C-peptide ratio) was 6.1 +/- 3.2% in patients with pancreatic cancer and 2.5 +/- 1.0% in control subjects (p < 0.05), while it was not associated with the diabetic pattern in OGTT. The sigma proinsulin/sigma C-peptide ratio was not associated with tumor size, location or resectability but was associated with the number of islets left within or close to cancer stroma. The increased sigma proinsulin/sigma C-peptide ratio decreased after tumor removal.

Conclusions: Patients with pancreatic cancer are characterized by increased proinsulin secretion and decreased C-peptide production during OGTT probably due to impaired proinsulin conversion. Although further studies are required in a large scale of patients, measurement of proinsulin and C-peptide levels during OGTT should serve as an early marker to identify high risk groups of the disease.