Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia

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Adiels , M , Taskinen , M-R , Björnson , E , Andersson , L , Matikainen , N , Söderlund , S , Kahri , J , Hakkarainen , A , Lundbom , N , Sihlbom , C , Thorsell , A , Zhou , H , Pietiläinen , K H , Packard , C & Boren , J 2019 , ' Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia ' , Diabetes, obesity and metabolism , vol. 21 , no. 8 , pp. 1861-1870 . https://doi.org/10.1111/dom.13744

Title: Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
Author: Adiels, Martin; Taskinen, Marja-Riitta; Björnson, Elias; Andersson, Linda; Matikainen, Niina; Söderlund, Sanni; Kahri, Juhani; Hakkarainen, Antti; Lundbom, Nina; Sihlbom, Carina; Thorsell, Annika; Zhou, Haihong; Pietiläinen, Kirsi H.; Packard, Chris; Boren, Jan
Contributor organization: Research Programs Unit
CAMM - Research Program for Clinical and Molecular Metabolism
Faculty of Medicine
HUS Abdominal Center
Endokrinologian yksikkö
HUS Internal Medicine and Rehabilitation
Marja-Riitta Taskinen Research Group
Department of Medicine
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
Date: 2019-08
Language: eng
Number of pages: 10
Belongs to series: Diabetes, obesity and metabolism
ISSN: 1462-8902
DOI: https://doi.org/10.1111/dom.13744
URI: http://hdl.handle.net/10138/312925
Abstract: Aims To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5-H-2(3)]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 +/- 198 vs. 652 +/- 196 mg/d, P = 0.03) and apoC-III levels (10.0 +/- 3.8 vs. 11.7 +/- 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 +/- 208 vs. 505 +/- 174 mg/d, P = 0.042). Conclusions The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III.
Subject: apolipoprotein C-III
kinetics
lipoproteins
stable isotopes
type 2 diabetes
LOW-DENSITY-LIPOPROTEIN
TRIGLYCERIDE-RICH LIPOPROTEIN
OF-FUNCTION MUTATIONS
REMNANT CHOLESTEROL
CORONARY EVENTS
PLASMA
CIII
RISK
VLDL
METABOLISM
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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