NCT07246421招募中不适用
Mechanisms for Glucagon Resistance as Driver of Metabolic Associated Steatotic Liver Disease and Cardiovascular Disease in Humans With Type 2 Diabetes
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Hepatic FFA oxidation rate (µmol/100Ml/min)
研究概览
简要总结
The goal of this clinical trial is to investigate the sensitivity to glucagon in patients with type 2 diabetes mellitus (T2DM), with and without metabolic associated fatty liver disease (MASLD).
The main questions it aims to answer are:
- Is the sensitivity to glucagon with respect to hepatic FA oxidation and suppression of VLDL-TG secretion impaired in humans with T2DM and MASLD?
- Is glucagon resistance and MASLD reflected in an aberrated lipidomic/metabolomic profile in blood and adipose tissue?
Researchers will compare patients with T2DM with and without MASLD to see if the response to basal and high levels of glucagon differs between the groups.
Participants will attend 2 short visits and 1 full-day visit, including:
- Body scan (DXA) to check fat and bone composition
- MRI to measure liver fat.
- Blood tests.
- Ultrasound to check liver stiffness and scarring.
- Fat biopsies
- 8-hour hormone (including glucagon) and tracer infusion
- PET-CT scans
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI > 26 kg/m²
- •confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) min. 6 months prior enrollment
- •steatosis FF% > 5,6% on MR spectroscopy for MAFLD group
排除标准
- •Alcohol abuse (>10 units per week for both sexes) or other substance abuse
- •Current or previous malignant disease
- •Blood donation within the last 3 months prior to the study day
- •Participation in studies involving radioactive isotopes within the past 3 months
- •Pregnancy
- •Severely dysregulated type 2 diabetes mellitus (haemoglobin A1c ≥ 100 mmol/mol)
- •C-peptide < 200 pmol/L
- •Previous acute myocardial infarction (AMI)
- •Clinical symptoms of heart failure
- •Current or previous malignant disease
- •Known ongoing systemic disease, except for dyslipidaemia and hypertension
- •Regular use of medication that may affect lipid and glucose metabolism, including insulin treatment, regular use of over-the-counter medications, and hormonal contraception. Exceptions:
- •Participants treated with statins may be included following a 2-week washout period prior to the experimental study day.
- •Participants receiving oral glucose-lowering therapy for T2DM and antihypertensive medication may be included provided that medication is withheld on the study day only.
- •Participants receiving weekly injectable glucagon-like peptide-1 receptor agonists (GLP-1 analogues) may be included following a 1-week washout period prior to the study day.
研究组 & 干预措施
Subjects with T2DM and MR spectroscopy verified steatosis
Active Comparator
干预措施: Glugagon (Other)
Subjects with T2DM and MR spectroscopy verified NO steatosis
Active Comparator
干预措施: Glugagon (Other)
结局指标
主要结局
Hepatic FFA oxidation rate (µmol/100Ml/min)
时间窗: 30 minutes at steady-state
Measured using \[11C\]palmitate positron-emission tomography (PET)
Blood and adipose tissue proteomic and lipidomic profiles
时间窗: 30 minutes after steady-state
Mass spectrometry-based lipidomic/proteomic profiles of paired adipose and plasma samples.
次要结局
- Endogen glucose production (mmol/kg/min)(30 minutes at steady-state)
- Fatty acid turnover (µmol/min)(30 minutesat steady-state)
- VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min))(30 minutes at steady-state)
研究者
研究点 (2)
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