Document Detail


The effect of dipeptidyl peptidase-4 inhibition on gastric volume, satiation and enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled crossover study.
MedLine Citation:
PMID:  18331607     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The incretin hormone glucagon-like peptide-1 (GLP-1) retards gastric emptying and decreases caloric intake. It is unclear whether increased GLP-1 concentrations achieved by inhibition of the inactivating enzyme dipeptidyl peptidase-4 (DPP-4) alter gastric volumes and satiation in people with type 2 diabetes.
METHODS: In a double-blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50 mg bid) or placebo for 10 days in random order separated by a 2-week washout. On day 7, fasting and postmeal gastric volumes were measured by a (99m)Tc single-photon emission computed tomography (SPECT) method. On day 8, a liquid Ensure meal was consumed at 30 ml/min, and maximum tolerated volume (MTV) and symptoms 30 min later were measured using a visual analogue scale (VAS) to assess effects on satiation. On day 10, subjects ingested water until maximum satiation was achieved. The volume ingested was recorded and symptoms similarly measured using a VAS.
RESULTS: Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 +/- 21 vs. 247 +/- 19 ml, P = 0.98) and fed (746 +/- 28 vs. 772 +/- 26 ml, P = 0.54) gastric volumes did not differ when subjects received vildagliptin or placebo. Treatment with vildagliptin did not alter the MTV of Ensure (1657 +/- 308 vs. 1389 +/- 197 ml, P = 0.15) or water compared to placebo (1371 +/- 141 vs. 1172 +/- 156 ml, P = 0.23). Vildagliptin was associated with decreased peptide YY (PYY) concentrations 60 min after initiation of the meal (166 +/- 27 vs. 229 +/- 34 pmol/l, P = 0.01).
CONCLUSIONS: Vildagliptin does not alter satiation or gastric volume in people with type 2 diabetes despite elevated GLP-1 concentrations. Compensatory changes in enteroendocrine secretion could account for the lack of gastrointestinal symptoms.
Authors:
Adrian Vella; Gerlies Bock; Paula D Giesler; Duane B Burton; Denise B Serra; Monica Ligueros Saylan; Carolyn F Deacon; James E Foley; Robert A Rizza; Michael Camilleri
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-03-10
Journal Detail:
Title:  Clinical endocrinology     Volume:  69     ISSN:  1365-2265     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-05     Completed Date:  2009-08-20     Revised Date:  2014-06-01    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  737-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adamantane / analogs & derivatives*,  pharmacology
Cross-Over Studies
Diabetes Mellitus, Type 2 / metabolism,  pathology*
Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
Double-Blind Method
Drinking / physiology
Eating / physiology
Enteroendocrine Cells / drug effects*,  secretion
Fasting / blood,  metabolism
Gastric Emptying / drug effects,  physiology
Ghrelin / blood
Glucagon-Like Peptide 1 / blood
Humans
Hypoglycemic Agents / pharmacology
Middle Aged
Nitriles / pharmacology*
Organ Size / drug effects
Placebos
Postprandial Period / drug effects
Pyrrolidines / pharmacology*
Satiation / drug effects*,  physiology
Stomach / drug effects*,  pathology
Grant Support
ID/Acronym/Agency:
DK02638/DK/NIDDK NIH HHS; DK078646/DK/NIDDK NIH HHS; DK29953/DK/NIDDK NIH HHS; P01 DK068055/DK/NIDDK NIH HHS; P01-DK068055/DK/NIDDK NIH HHS; R01 DK078646/DK/NIDDK NIH HHS; RR024150/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Dipeptidyl-Peptidase IV Inhibitors; 0/Ghrelin; 0/Hypoglycemic Agents; 0/Nitriles; 0/Placebos; 0/Pyrrolidines; 89750-14-1/Glucagon-Like Peptide 1; I6B4B2U96P/vildagliptin; PJY633525U/Adamantane
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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