Suppression of -Cell Secretion by Somatostatin Does Not Fully Reverse the Disproportionate Proinsulinemia of Type 2 Diabetes

Disproportionate hyperproinsulinemia is a feature of -cell dysfunction in type 2 diabetes. It has been hypothesized that this abnormality represents an intrinsic abnormality of the -cell and/or may result from an increase in -cell secretory demand. To address this, six patients with type 2 diabetes and six ageand BMImatched normal subjects received a combined 3-h insulin and somatostatin clamp to decrease -cell secretory demand. An arginine stimulation test was performed before and at the end of the clamp to measure -cell peptide release. In keeping with the reduction in secretory demand, C-peptide levels were suppressed by 60– 80% during the clamp, as were proinsulin (PI) levels. The arginine-stimulated PI/C-peptide ratio decreased in the diabetic subjects from 4.4 1.5% before to 1.8 0.5% after the clamp (P < 0.01). This latter ratio was similar to that observed in the normal subjects before the somatostatin infusion (1.5 0.3%). In the normal subjects, after the clamp the PI/C-peptide ratio had decreased to 0.8 0.3% (P < 0.01). Thus, the postclamp PI/C-peptide ratio in the subjects with type 2 diabetes was elevated compared with that in the normal subjects (P < 0.05). Based on these observations, while relief of secretory demand on -cells by somatostatin decreases the disproportionate elevation in PI levels in patients with type 2 diabetes, the failure to normalize this measure suggests that an intrinsic abnormality of -cell function exists in subjects with type 2 diabetes that may be aggravated by increased secretory demand. Diabetes 53 (Suppl. 3):S22–S25, 2004