Randomized, Controlled Trial Of Sitagliptin And Islet Function In Cystic Fibrosis With Abnormal Glucose Tolerance.

Like Comment
Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) concentrations augment insulin secretion and glucagon suppression and lower post-prandial glycemia in PI-CF with AGT.Twenty-six adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT (defined by oral glucose tolerance test glucose [mg/dL]: early glucose intolerance [1-hour ≥155 & 2-hour <140], impaired glucose tolerance [2-hour ≥140 and <200 mg/dl], or diabetes [2-hour ≥200]) were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched-placebo; 24 completed the trial (n=12 sitagliptin; n=12 placebo). Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISR), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of β- and α-cell function.Following 6-months of sitagliptin vs. placebo, MMTT intact GLP-1 and GIP responses increased (P <0.001), ISR dynamics improved (P <0.05), and glucagon suppression was modestly enhanced (P <0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or β-cell sensitivity to glucose, including for second-phase insulin response were found.In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting post-prandial glycemia.

View the full article @ The Journal of clinical endocrinology and metabolism

Get PDF with LibKey
Authors: Andrea Kelly, Saba Sheikh, Darko Stefanovski, Amy J Peleckis C R N P, Sarah C Nyirjesy, Jack N Eiel, Aniket Sidhaye, Russell Localio, Robert Gallop, Diva D De Leon, Denis Hadjiliadis, Ronald C Rubenstein, Michael R Rickels


The wider, wiser view for healthcare professionals. ClinOwl signposts the latest clinical content from over 100 leading medical journals.
6577 Contributions
0 Following