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Lixisenatide reduces chylomicron triacylglycerol due to increased clearance

Whyte, Martin B, Shojaee-Moradie, Fariba, Sharaf, Sharaf E, Jackson, Nicola, Fielding, Barbara, Hovorka, Roman, Mendis, Jeewaka, Russell-Jones, David and Umpleby, A Margot (2018) Lixisenatide reduces chylomicron triacylglycerol due to increased clearance The Journal of Clinical Endocrinology & Metabolism, 104 (2). pp. 359-368.

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Context GLP-1 agonists control postprandial glucose and lipid excursion in type 2 diabetes; however the mechanism(s) are unclear. Objective To determine the mechanism(s) of postprandial lipid and glucose control with lixisenatide (GLP-1 analogue) in type 2 diabetes. Design Randomised, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, UK Patients Eight obese men with type 2 diabetes (57.3±1.9yrs; BMI 30.3±1.0kg/m2, HbA1C 66.5±2.6mmol/mol, [8.2±0.3%]). Interventions Two metabolic studies, four-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 iv bolus of [2H5]glycerol in a 12h study, with hourly feeding. Oral [13C]triolein, in a single meal, labelled 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 AUC60-480min 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 rate (Ra) (P=0.015), Rameal (P=0.0098) and acetaminophen AUC0-360min (P=0.006) were lower with lixisenatide than placebo. Conclusions Lixisenatide reduced [13C]oleate concentration, derived from a single meal in CM-TAG, as well as glucose Rameal, through delayed gastric emptying. However day-long CM production, measured with repeated meal-feeding, was not reduced by lixisenatide and decreased CM-TAG concentration was due to increased CM-TAG clearance.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Whyte, Martin
Shojaee-Moradie, Fariba
Sharaf, Sharaf E
Hovorka, Roman
Mendis, Jeewaka
Umpleby, A
Date : 11 September 2018
DOI : 10.1210/jc.2018-01176
Copyright Disclaimer : Copyright © 2018 Endocrine Society
Uncontrolled Keywords : Lixisenatide; GLP-1 agonist; Postprandial hyperlipidaemia; Lipoprotein
Depositing User : Clive Harris
Date Deposited : 02 Oct 2018 15:11
Last Modified : 12 Sep 2019 02:08

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