181 Loss of the incretin effect in cystic fibrosis related diabetes (CFRD)

Abstract

Objectives The hallmark of dysglycaemia in CFRD is postprandial glucose excursions, normally the major physiological determinant of insulin release after meals are the incretin hormones (GLP1+GIP) however little is known about their functioning in individuals with CF. Methods To assess whether incretin hormones enhance insulin secretion at any given glucose level (i.e. the incretin effect) participants underwent a modified 50 g oral glucose tolerance test (OGTT) and then separately a matched intravenous isoglycemic clamp (IIC). A group of patients with significant dysglycemia (either positive OGTT or Continuous glucose monitoring; and requiring treatment with insulin) was compared to a normoglycemic group. Results 9 pancreatic insufficient participants (CFRD = 4) underwent OGTT the results of which were matched accurately during the IIC (no difference on ANOVA at 0.05 significance). The nondiabetic group had significantly higher insulin secretion during the OGTT compared to the IIC despite having matched glucose levels in both tests, demonstrating an intact incretin effect (relative increase +43%). The diabetic group, despite producing comparable amounts of incretin hormones, failed to show an appropriate rise in insulin secretion. TableResponses during OGTT + matched isoglycemic clampCFRDNondiabeticMean AUC glucose (mmol/l/4 hr)836.4617.7Incremental Active GLP1 (pM/2 hr)214.2203.0Incremental GIP (pg/ml/2 hr)25071.723342.1Insulin response during IIC (uU/ml/2 hr)1673.11596.2Insulin response to OGTT (uU/ml/2 hr)1634.62286.0Incretin effect (relative % increase insulin)−2%+43% Conclusion We have shown for the first time using an isoglycemic clamp that the incretin effect is lost in CFRD, and although incretin hormones are produced appropriately there is a failure of beta cells to respond.