Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Diabetes Obes Metab. 2019 Aug;21(8):1861-1870. doi: 10.1111/dom.13744. Epub 2019 May 8.
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- H ]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.
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.
研究 2 型糖尿病患者载脂蛋白 C-III（apoC-III）代谢如何改变，这种情况下受干扰的血浆甘油三酯浓度主要是由 apoC-III 的分泌率还是清除率决定，以及使用胰高血糖素样肽-1 类似物利拉鲁肽 16 周改善血糖控制是否会改变 apoC-III 动力学。
使用超灵敏质谱技术，在给予 [5,5,5- H ]亮氨酸的餐后，评估 apoC-III 的动力学。我们比较了两种情况的 apoC-III 动力学：在接受利拉鲁肽治疗前后的 2 型糖尿病患者，以及具有匹配体重指数（BMI）的 2 型糖尿病非糖尿病患者。使用质子磁共振波谱法测定肝脂肪含量、皮下腹部和腹内脂肪。
利拉鲁肽治疗 16 周可显著降低 2 型糖尿病患者的血糖控制水平，从而降低 apoC-III 的分泌率（561 ± 198 比 652 ± 196mg/d，P=0.03）和 apoC-III 水平（10.0 ± 3.8 比 11.7 ± 4.3mg/dL，P=0.035）。apoC-III 分泌率的变化与葡萄糖控制指数的改善显著相关（r=0.67；P=0.009）和甘油三酯曲线下面积的变化相关（r=0.59；P=0.025）。与此一致的是，与 BMI 匹配的非糖尿病患者相比，2 型糖尿病患者的 apoC-III 分泌率更高（676 ± 208 比 505 ± 174mg/d，P=0.042）。
结果表明，apoC-III 的分泌率与 2 型糖尿病患者的甘油三酯-rich 脂蛋白升高有关，这可能是通过葡萄糖稳态对 apoC-III 产生的影响。
