Impaired insulin secretion in response to mixed meal ingestion is associated with hypersomatostatinemia in individuals with cystic fibrosis.

Cystic fibrosis (CF) is a monogenic disease characterized by exocrine pancreas insufficiency, glucose intolerance, and a high prevalence of diabetes. Diminished insulin secretion is a key contributor to glucose intolerance and diabetes in people with CF, yet the pathophysiology of this deficiency is not fully understood. Somatostatin is a hormone secreted by several tissues in the body, including the delta cells of the pancreas, and is known to inhibit insulin secretion; however, its role in postprandial hypoinsulinemia in people with CF remains unclear. This cross-sectional study included 16 people with CF (CF group) and 8 healthy control subjects (HC), each of whom underwent a mixed meal tolerance test, during which their glucoregulatory responses were assessed. We hypothesized that impaired insulin secretion in CF would be associated with hypersomatostatinemia. Plasma glucose responses to the mixed meal were higher in CF compared to HC (AUC of 27,656±2,215 and 20,564±1,028 mg/dL*180 min, respectively, p<0.05), whereas the AUC for insulin (5866±730 and 11090±1628 µU/mL*180 min, respectively; p<0.05), and C-peptide (608±42 and 998±127 pg/mL*180 min, respectively; p<0.05), were both lower. Hypersomatostatinemia in CF (AUC of 4682±278 and 3353±277 pg/mL*180 min in CF and HC, respectively, p<0.01), was inversely associated with C-peptide (r=-0.54; p<0.01), and insulin (r=-0.60; p<0.01) responses to the mixed meal. These data suggest that hypersomatostatinemia is associated with diminished insulin secretion in people with CF, and that it could be a target for improving glucose tolerance in this population.