WS04.1 Hypersecretion of glucagon-like peptide 1 (GLP1) in cystic fibrosis

Abstract

Objectives GLP1, an incretin hormone important in post-prandial glucose regulation, is inactivated by enzymes which may be up-regulated in inflammatory conditions such as CF. We looked for evidence of incretin inactivation in individuals with and without CF-related diabetes (CFRD). Methods GLP1 levels (total & active) were measured during stimulation (oral glucose tolerance test) in 10 individuals with CF (5 CFRD) whilst clinically stable and compared to a matched control group. Samples were processed with DPP4 inhibitor using an ELISA assay (Millipore, Germany). Results Baseline circulating levels of both active and total GLP1 were similar in all groups. Total GLP1 responses were most pronounced in the CFRD group whose levels rose most sharply; peaked highest and then returned to baseline quicker than the remaining CF patients who in turn had a higher and more sustained rise than controls. Both CF groups therefore significantly hypersecreted total GLP1 (p CFRD (n = 5) Nondiabetics (n = 5) Controls (n = 6) Baseline GLP1 levels 12.9 (2.5) 11.4 (3.0) 10.0 (2.5) Peak GLP1 27.0 (7.9) 22.8 (7.2) 13.1 (6.3) Time to peak GLP1 (min) 30 (15) 45 (45) 30 (30) % total secretion 0–30 min 78% (65%) 51% (47%) 61% (49%) % total secretion 0–60 min 100% (92%) 91% (91%) 95% (97%) Total incremental rise in GLP1 448.6 (203.0) 736.9 (272.4) 178.1 (167.1) Values in parentheses are active levels. Conclusion Individuals with CF, irrespective of glycemic status, hypersecrete total GLP1 to achieve similar levels of active hormone seen in matched controls. This suggests that CF is associated with higher levels of incretin degradation even in stable non-diabetic patients. Delayed insulin release – common in CFRD – may contribute to the high peaks of GLP1 seen in this group, as normal physiological negative feedback will be lost.