PMID- 34406395
OWN - NLM
STAT- MEDLINE
DCOM- 20211110
LR  - 20220418
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 9
DP  - 2021 Aug 18
TI  - Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic 
      Fibrosis With Abnormal Glucose Tolerance.
PG  - 2617-2634
LID - 10.1210/clinem/dgab365 [doi]
AB  - PURPOSE: 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 postprandial glycemia in 
      PI-CF with AGT. METHODS: 26 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-h >/= 155 and 
      2-h < 140), impaired glucose tolerance (2-h >/= 140 and < 200 mg/dL), or diabetes 
      (2-h >/= 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 (ISRs), 
      glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) 
      test-derived measures of beta- and alpha-cell function. RESULTS: 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 beta-cell sensitivity to glucose, including for 
      second-phase insulin response, were found. CONCLUSIONS: In glucose intolerant 
      PI-CF, sitagliptin intervention augmented meal-related incretin responses with 
      improved early insulin secretion and glucagon suppression without affecting 
      postprandial glycemia.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Kelly, Andrea
AU  - Kelly A
AUID- ORCID: 0000-0003-1724-9868
AD  - Division of Endocrinology and Diabetes, Department of Pediatrics, Children's 
      Hospital of Philadelphia, Philadelphia, PA, USA.
FAU - Sheikh, Saba
AU  - Sheikh S
AD  - Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphias, PA, USA.
FAU - Stefanovski, Darko
AU  - Stefanovski D
AD  - Department of Biostatistics, University of Pennsylvania School of Veterinary 
      Medicine, Kennett Square, PA, USA.
FAU - Peleckis, Amy J
AU  - Peleckis AJ
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, 
      Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Nyirjesy, Sarah C
AU  - Nyirjesy SC
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, 
      Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Eiel, Jack N
AU  - Eiel JN
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, 
      Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Sidhaye, Aniket
AU  - Sidhaye A
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Localio, Russell
AU  - Localio R
AD  - Department of Biostatistics, University of Pennsylvania School of Medicine, 
      Philadelphia, PA, USA.
FAU - Gallop, Robert
AU  - Gallop R
AD  - Department of Biostatistics, University of Pennsylvania School of Medicine, 
      Philadelphia, PA, USA.
AD  - Department of Mathematics, West Chester University of Pennsylvania, West Chester, 
      PA, USA.
FAU - De Leon, Diva D
AU  - De Leon DD
AD  - Division of Endocrinology and Diabetes, Department of Pediatrics, Children's 
      Hospital of Philadelphia, Philadelphia, PA, USA.
FAU - Hadjiliadis, Denis
AU  - Hadjiliadis D
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Rubenstein, Ronald C
AU  - Rubenstein RC
AD  - Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphias, PA, USA.
AD  - Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington 
      University in St. Louis School of Medicine, St. Louis, MO, USA.
FAU - Rickels, Michael R
AU  - Rickels MR
AUID- ORCID: 0000-0002-9253-838X
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, 
      Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01879228
GR  - UL1 TR001878/TR/NCATS NIH HHS/United States
GR  - R01 DK97830/NH/NIH HHS/United States
GR  - K23 DK107937/DK/NIDDK NIH HHS/United States
GR  - R56 DK097830/DK/NIDDK NIH HHS/United States
GR  - R01 DK097830/DK/NIDDK NIH HHS/United States
GR  - T32 DK007314/DK/NIDDK NIH HHS/United States
GR  - P30 DK019525/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210522
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 9007-92-5 (Glucagon)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
CIN - J Clin Endocrinol Metab. 2021 Jun 17;:null. PMID: 34139767
EIN - J Clin Endocrinol Metab. 2021 Oct 15;:. PMID: 34652439
EIN - J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1778. PMID: 34792139
MH  - Adolescent
MH  - Adult
MH  - Cystic Fibrosis/*complications
MH  - Dipeptidyl-Peptidase IV Inhibitors/*pharmacology
MH  - Double-Blind Method
MH  - Exocrine Pancreatic Insufficiency/*drug therapy/physiopathology
MH  - Female
MH  - Glucagon/blood
MH  - Glucose Intolerance/*drug therapy/physiopathology
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Insulin Secretion/drug effects
MH  - Islets of Langerhans/*drug effects/physiology
MH  - Male
MH  - Sitagliptin Phosphate/*pharmacology/therapeutic use
MH  - Young Adult
PMC - PMC8660013
OTO - NOTNLM
OT  - DPP-4
OT  - abnormal glucose tolerance
OT  - cystic fibrosis
OT  - dipeptidyl peptidase-4 inhibitor
OT  - glucagon
OT  - glucagon-like peptide-1
OT  - glucose dependent insulinotropic polypeptide
OT  - incretin
OT  - insulin
EDAT- 2021/08/19 06:00
MHDA- 2021/11/11 06:00
PMCR- 2021/05/22
CRDT- 2021/08/18 12:28
PHST- 2021/03/22 00:00 [received]
PHST- 2021/08/18 12:28 [entrez]
PHST- 2021/08/19 06:00 [pubmed]
PHST- 2021/11/11 06:00 [medline]
PHST- 2021/05/22 00:00 [pmc-release]
AID - 6281094 [pii]
AID - dgab365 [pii]
AID - 10.1210/clinem/dgab365 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Aug 18;106(9):2617-2634. doi: 
      10.1210/clinem/dgab365. Epub 2021 May 22.