Rajeev Surya Panicker, Sprung Victoria S, Roberts Carl, Harrold Jo A, Halford Jason C G, Stancak Andrej, Boyland Emma J, Kemp Graham J, Cuthbertson Daniel J, Wilding John P H
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
BMJ Open. 2017 Jan 27;7(1):e013539. doi: 10.1136/bmjopen-2016-013539.
Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy (H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI).
This outpatient study will evaluate the effect of dapagliflozin (10 mg), compared with placebo, on food intake and energy expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT).
This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP).
ISRCTN14818531. EUDRACT number 2013-004264-60.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是有效的降糖药物，对2型糖尿病（T2DM）患者的体重有有益影响。然而，观察到的体重减轻低于根据定量糖尿预测的体重减轻，这表明能量摄入有代偿性增加或能量消耗减少。使用双能X线吸收法（DEXA）的研究表明，大多数体重变化是由于脂肪组织的减少，但脂肪含量的器官特异性变化（如肝脏、骨骼肌）尚未确定。在这项随机、双盲、安慰剂对照的交叉研究中，我们旨在研究使用SGLT2抑制剂达格列净时伴随的能量摄入、饮食行为和能量消耗的代偿性变化。此外，我们旨在使用MRI定量脂肪分布的变化，使用质子磁共振波谱（H-MRS）定量肝脏脂肪的变化，并使用血氧水平依赖（BOLD）功能磁共振成像（fMRI）定量中枢神经系统（CNS）对食物图像的反应变化。
这项门诊研究将评估达格列净（10毫克）与安慰剂相比，在7天和12周时对食物摄入和能量消耗的影响。52例T2DM患者将被随机分配到达格列净组或安慰剂组，进行参与者内交叉设计的短期和长期试验干预。主要结局是达格列净和安慰剂在测试餐期间能量摄入的差异。使用操作通用饮食监测仪（UEM）的定制程序自动收集摄入数据。次要结局包括：（1）食欲调节指标，包括进食速度、饱腹感商数、食欲评分（餐间和餐内）、使用BOLD-fMRI测量的CNS对食物图像反应的变化；（2）能量消耗指标；（3）身体成分变化，包括肝脏脂肪、腹部内脏脂肪组织（VAT）和皮下脂肪组织（SAT）的变化。
本研究已获得西北利物浦中央研究伦理委员会（14/NW/0340）的批准，并按照《赫尔辛基宣言》和《良好临床实践》（GCP）进行。
ISRCTN14818531。欧盟临床试验编号2013-004264-60。
