Johansen Rakel F, Søndergaard Esben, Sørensen Lars Peter, Nellemann Birgitte, Christiansen Jens S, Nielsen Søren
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark,
Diabetologia. 2015 Feb;58(2):355-62. doi: 10.1007/s00125-014-3422-6. Epub 2014 Nov 11.
AIMS/HYPOTHESIS: In type 1 diabetes, abnormalities of both glucose and lipoprotein metabolism are seen. The relationship between these factors is not understood, but studies indicate that hyperglycaemia may increase hepatic VLDL-triacylglycerol (VLDL-TG) secretion and reduce VLDL-TG fatty acid oxidation, which could lead to the development of dyslipidaemia. The aim of this study was to determine the isolated effect of hyperglycaemia on VLDL-TG and NEFA kinetics in men with type 1 diabetes.
VLDL-TG and palmitate kinetics were measured in eight men with type 1 diabetes using ex vivo labelled VLDL-TG and palmitate tracers. A 2.5 h basal period (plasma glucose 5 mmol/l) was followed by a 4 h hyperglycaemic period (plasma glucose 16 mmol/l). Steady-state VLDL-TG kinetics (VLDL-TG secretion, clearance and oxidation rates) were assessed by an isotope dilution technique using an intravenous primed-constant infusion of ex vivo labelled [1-(14)C]VLDL-TG in combination with sampling of blood and expired air. Palmitate turnover was measured using [9,10-(3)H]palmitate.
The VLDL-TG secretion rate (36.0 ± 9.6 vs 30.8 ± 6.1 μmol/min, NS) and clearance rate (209 ± 30.4 vs 197 ± 41.7 ml/min, NS) were unchanged during the basal and hyperglycaemic periods, resulting in unchanged VLDL-TG concentrations (0.25 ± 0.11 μmol/l vs 0.28 ± 0.10 μmol/l, NS). In addition, VLDL-TG fatty acid oxidation and palmitate flux were not changed during hyperglycaemia.
CONCLUSIONS/INTERPRETATION: Four hours of acute hyperglycaemia (16 mmol/l) without a concomitant increase in insulin does not alter VLDL-TG and NEFA kinetics in men with type 1 diabetes.
NCT01178957.
目的/假设：在1型糖尿病中，可见葡萄糖和脂蛋白代谢均异常。这些因素之间的关系尚不清楚，但研究表明，高血糖可能会增加肝脏极低密度脂蛋白三酰甘油（VLDL-TG）的分泌，并降低VLDL-TG脂肪酸氧化，这可能导致血脂异常的发生。本研究的目的是确定高血糖对1型糖尿病男性患者VLDL-TG和非酯化脂肪酸（NEFA）动力学的单独影响。
使用体外标记的VLDL-TG和棕榈酸示踪剂，对8名1型糖尿病男性患者的VLDL-TG和棕榈酸动力学进行测量。先进行2.5小时的基础期（血浆葡萄糖5 mmol/l），随后是4小时的高血糖期（血浆葡萄糖16 mmol/l）。通过同位素稀释技术，静脉注射体外标记的[1-(14)C]VLDL-TG并结合采血和收集呼出气体，评估稳态VLDL-TG动力学（VLDL-TG分泌、清除和氧化率）。使用[9,10-(3)H]棕榈酸测量棕榈酸周转率。
基础期和高血糖期的VLDL-TG分泌率（36.0±9.6对30.8±6.1 μmol/min，无显著差异）和清除率（209±30.4对197±41.7 ml/min，无显著差异）均未改变，导致VLDL-TG浓度不变（0.25±0.11 μmol/l对0.28±0.10 μmol/l，无显著差异）。此外，高血糖期间VLDL-TG脂肪酸氧化和棕榈酸通量未发生变化。
结论/解读：4小时急性高血糖（16 mmol/l）且胰岛素未随之增加，不会改变1型糖尿病男性患者的VLDL-TG和NEFA动力学。
NCT01178957。
