EPS4.06 Alterations in incretin and somatostatin levels by glucose tolerance status in people with cystic fibrosis

Objectives: Insulin deficiency in cystic fibrosis (CF) leads to CF related diabetes (CFRD), and dysregulation of other enteroendocrine hormones may further impair insulin secretion in CF. This study investigated whether glucose intolerance was associated with altered incretin or somatostatin secretion in adults with CF. Methods: We conducted a cross-sectional study using multiple-sample oral glucose tolerance tests (OGTTs) at the Copenhagen CF Center, Denmark. Samples were analyzed for total gastric inhibitory polypeptide (GIP), total glucagon-like peptide-1 (GLP-1), and somatostatin, and participants were categorized by their glucose tolerance status. We assessed the 0–120 minutes net incremental area under the curve (iAUC) above baseline for incretins and the 0–60 minutes net iAUC above baseline for somatostatin. Results: We included 93 participants with incretin data. Of these, somatostatin data were available for 70 participants. Both AUC0–120 of GIP and GLP1 were higher among those with CFRD than those with NGT (16 ng/mL/min [5; 27] vs. 27 ng/mL/min [16; 38], p = 0.04) and (435 pmol/L/min [32; 839] vs. 773 pmol/L/min [420; 1,126], p = 0.04). However, there was no linear association between glucose tolerance and net iAUC0–120 for any of the incretins. The net iAUC0–60 of somatostatin was – 164 pmol/L/min [–368; 38] among those with NGT, while it was 2 pmol/L/min [–75; 79] among those with CFRD. Moreover, net iAUC0–60 of somatostatin tended to be positively associated with glucose intolerance status (p-value for trend: 0.07). Conclusion: People with CFRD did not seem to have insufficient incretin levels during an OGTT and, in fact, glucose intolerance seemed to be associated with a compensatory increase in incretin levels. However, somatostatin secretion seemed to increase with worsening in glucose tolerance, which might suggest a relative suppression of insulin secretion in those with impaired glucose tolerance.