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dc.contributor.authorWhyte, Martin B
dc.contributor.authorShojaee-Moradie, Fariba
dc.contributor.authorSharaf, Sharaf E
dc.contributor.authorJackson, Nicola C
dc.contributor.authorFielding, Barbara
dc.contributor.authorHovorka, Roman
dc.contributor.authorMendis, Jeewaka
dc.contributor.authorRussell-Jones, David
dc.contributor.authorUmpleby, A Margot
dc.date.accessioned2019-03-20T14:50:02Z
dc.date.available2019-03-20T14:50:02Z
dc.date.issued2019-02-01
dc.identifier.issn0021-972X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290711
dc.description.abstractCONTEXT: Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. OBJECTIVE: To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. DESIGN: Randomized, double-blind, cross-over study. SETTING: Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. PATIENTS: Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. INTERVENTIONS: Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. MAIN OUTCOME MEASURES: Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. RESULTS: Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60-480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0-360min (P = 0.006) were lower with lixisenatide than with placebo. CONCLUSIONS: Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.
dc.format.mediumPrint
dc.languageeng
dc.publisherThe Endocrine Society
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectBlood Glucose
dc.subjectTriglycerides
dc.subjectChylomicrons
dc.subjectPeptides
dc.subjectHypoglycemic Agents
dc.subjectMetabolic Clearance Rate
dc.subjectTreatment Outcome
dc.subjectCross-Over Studies
dc.subjectDouble-Blind Method
dc.subjectGastric Emptying
dc.subjectPostprandial Period
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectGlucagon-Like Peptide-1 Receptor
dc.titleLixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance.
dc.typeArticle
prism.endingPage368
prism.issueIdentifier2
prism.publicationDate2019
prism.publicationNameJ Clin Endocrinol Metab
prism.startingPage359
prism.volume104
dc.identifier.doi10.17863/CAM.37911
dcterms.dateAccepted2018-09-06
rioxxterms.versionofrecord10.1210/jc.2018-01176
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-02
dc.contributor.orcidHovorka, Roman [0000-0003-2901-461X]
dc.identifier.eissn1945-7197
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-09-11


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