Role of apolipoprotein C-III overproduction in diabetic dyslipidemia

Adiels, M. et al. (2019) Role of apolipoprotein C-III overproduction in diabetic dyslipidemia. Diabetes, Obesity and Metabolism, 21(8), pp. 1861-1870. (doi: 10.1111/dom.13744) (PMID:30972934)

185159.pdf - Accepted Version



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 [5,5,5‐2H3]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.

Item Type:Articles
Additional Information:This project was funded by IIS grants from NovoNordisk and grants from the Swedish Heart‐Lung Foundation, Swedish Diabetes Foundation, Swedish Research Council, Swedish Foundation for Strategic Research, Sahlgrenska University Hospital, Sigrid Juselius Foundation, Helsinki University Hospital Research funds, EU project RESOLVE, and Finnish Heart Foundation, the Academy of Finland (grant numbers: 314383, 272376, 266286), Finnish Medical Foundation, Gyllenberg Foundation, Finnish Diabetes Research Foundation, and Novo Nordisk Foundation.
Keywords:ApoC-III, kinetics, lipoproteins, stable isotopes, type 2 diabetes.
Glasgow Author(s) Enlighten ID:Packard, Professor Chris
Authors: 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., and Borén, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetes, Obesity and Metabolism
ISSN (Online):1463-1326
Published Online:10 April 2019
Copyright Holders:Copyright © 2019 John Wiley & Sons
First Published:First published in Diabetes, Obesity and Metabolism 21(8):1861-1870
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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