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: University of Helsinki, Research Programs Unit
University of Helsinki, HUS Abdominal Center
University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism
University of Helsinki, HUS Internal Medicine and Rehabilitation
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, HUS Abdominal Center
Date: 2019-08
Language: eng
Number of pages: 10
Belongs to series: Diabetes, obesity and metabolism
ISSN: 1462-8902
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
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