Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

• Published in: Diabetes, obesity & metabolism Vol. 21; no. 8; pp. 1861 - 1870
• Main Authors: 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, Borén, Jan
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2019; Wiley Subscription Services, Inc
• Subjects: apolipoprotein C‐III; Apolipoproteins; Body mass index; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Dyslipidemia; Endocrinology and Diabetes; Endokrinologi och diabetes; Glucagon; Homeostasis; kinetics; Leucine; Lipoproteins; Magnetic resonance spectroscopy; Mass spectroscopy; Metabolic disorders; Secretion; stable isotopes; type 2 diabetes; stable isotopes; type 2 diabetes; apolipoprotein C-III; kinetics; lipoproteins
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.13744

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.