Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, 14221, New york, USA.
Diabetes Obes Metab. 2020 Oct;22(10):1742-1752. doi: 10.1111/dom.14090. Epub 2020 Jul 8.
To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM).
A total of 84 adult overweight and obese patients with T1DM, with no detectable C-peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months. Blood samples were collected at 0, 12 and 26 weeks. Subcutaneous adipose tissue biopsies, a high-calorie high-fat meal challenge test, continuous glucose monitoring, dual-energy X-ray absorptiometry and MRI were performed before and at the end of treatment.
In all, 37 and 27 patients who received liraglutide and placebo, respectively, completed the study. Glycated haemoglobin fell by 0.41 ± 0.18% (4.5±1.4 mmol/mol) from baseline after liraglutide treatment (P = 0.001), and by 0.29 ± 0.19% (3.1±2.0 mmol/mol) compared to placebo (P = 0.1). There was no increase in hypoglycaemia, while the time spent in normal glycaemia increased (P = 0.015) and time spent in hyperglycaemia decreased (P = 0.019). Body weight fell significantly in the liraglutide group, mostly in the form of fat mass loss (including visceral fat), with no change in lean mass. Systolic blood pressure (SBP) also fell after liraglutide treatment. Liraglutide also caused a significant increase in the expression of adipose tissue triglyceride lipase, carnitine palmitoyl transferase-1, peroxisome proliferator-activated receptor (PPAR)α, PPARδ, uncoupling protein-2 and type 2 iodothyronine deiodinase in the adipose tissue.
Liraglutide improves glycaemia, reduces adiposity and SBP. Liraglutide also stimulates mechanisms involved with an increase in lipid oxidation and thermogenesis, while conserving lean body mass.
研究利拉鲁肽治疗对超重和肥胖 1 型糖尿病（T1DM）患者血糖控制和脂肪组织代谢的影响。
共纳入 84 例无可检测到 C 肽的成年超重和肥胖 T1DM 患者，随机（1:1）分为安慰剂组或 1.8 mg/d 利拉鲁肽组，治疗 6 个月。分别在 0、12 和 26 周时采集血样。在治疗前和治疗结束时进行皮下脂肪组织活检、高热量高脂肪餐挑战试验、连续血糖监测、双能 X 线吸收法和 MRI。
共有 37 例和 27 例接受利拉鲁肽和安慰剂治疗的患者完成了研究。与安慰剂相比，利拉鲁肽治疗后糖化血红蛋白下降 0.41±0.18%（4.5±1.4 mmol/mol，P=0.001），下降 0.29±0.19%（3.1±2.0 mmol/mol，P=0.1）。低血糖无增加，而正常血糖时间增加（P=0.015），高血糖时间减少（P=0.019）。利拉鲁肽组体重显著下降，主要表现为脂肪质量（包括内脏脂肪）减少，而瘦体重无变化。利拉鲁肽治疗后收缩压（SBP）也下降。利拉鲁肽还导致脂肪组织甘油三酯脂肪酶、肉毒碱棕榈酰转移酶-1、过氧化物酶体增殖物激活受体（PPAR）α、PPARδ、解偶联蛋白-2 和 2 型甲状腺素脱碘酶在脂肪组织中的表达显著增加。
利拉鲁肽改善血糖，减少肥胖和 SBP。利拉鲁肽还刺激与脂质氧化和产热增加相关的机制，同时保留瘦体重。
