👤 Nina Lundbom

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. Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 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). 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. Show less

A recent study in Indian subjects suggested common variants in apolipoprotein C3 (APOC3) (T-455C at rs2854116 and C-482T at rs2854117) to contribute to non-alcoholic fatty liver disease (NAFLD), plasma apoC3 and triglyceride concentrations. Our aim was to determine the contribution of genetic variation in APOC3 on liver fat content and plasma triglyceride and apoC3 concentrations in a larger European cohort. A total of 417 Finnish individuals were genotyped for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) influencing liver fat. Plasma apoC3 concentration was measured enzymatically, and liver fat by proton magnetic resonance spectroscopy. APOC3 wild-type homozygotes and variant allele (T-455C or C-482T or both) carriers did not differ with regard to liver fat, apoC3 concentrations, triglyceride-, high density lipoprotein-, fasting plasma glucose, insulin-, alanine aminotransferase- and aspartate aminotransferase-concentrations, nor was there a difference in prevalence of NAFLD. In contrast, carriers of the PNPLA3 GG genotype at rs738409 had a 2.7-fold (median 11.3%) higher liver fat than those with the CC (median 4.2%) genotype. The PNPLA3 rs738409 was also an independent predictor of liver fat, together with age, gender, and body mass index. Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD. Show less