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Role of apolipoprotein C-III overproduction in diabetic dyslipidemia

Martin Adiels, Marja-Riitta Taskinen, Elias Björnson, Linda Andersson, Niina Matikainen, Sanni Söderlund, Juhani Kahri, Antti Hakkarainen, Nina Lundbom, Carina Sihlbom, Annika Thorsell, Haihong Zhou, Kirsi H Pietiläinen, Chris Packard, Jan Borén
Diabetes, Obesity & Metabolism 2019 April 10

AIMS: ApoC-III is an important novel target underpinning the link between hypertriglyceridemia with cardiovascular disease. Here, we investigated how apoC-III metabolism is altered in subjects with type 2 diabetes, and focused on whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of this apoprotein. Second, we investigated whether improvement of glycemic control using the GLP-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics.

MATERIALS AND METHODS: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5-2 H3 ]leucine, using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations; in subjects with type 2 diabetes subjects before and after liraglutide therapy, and in type 2 diabetic and BMI-matched non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy.

RESULTS: Improved glycemic control by liraglutide therapy for 16 weeks reduced significantly apoC-III secretion rate (561±198 vs. 652±196 mg/day, p=0.03) and apoC-III levels (10.0±3.8 vs. 11.7±4.3 mg/dL, p=0.035) in type 2 diabetic subjects. Change in apoC-III secretion rate was associated significantly with the improvement in indices of glucose control (r=0.67; p=0.009) and change in triglyceride AUC (r=0.59; p=0.025). In line, 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/day, p=0.042).

CONCLUSIONS: The results reveal that the secretion rate of apoC-III associates with elevation of triglyceride-rich lipoproteins in type 2 diabetics, potentially through the influence of glucose homeostasis on the production of apoC-III. This article is protected by copyright. All rights reserved.


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