Hypoglycaemia and Cardiac Arrhythmias in Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Part 1: Clinically relevant arrhythmias
研究概览
简要总结
Twenty-one patients with insulin-treated type 2 diabetes with diabetic complications will be recruited to Part 1 of the study, a three-hour combined hyper- and hypoglycaemic clamp, along with a control group of twenty-one individuals with normal glucose tolerance matched for age, gender, and body mass index. Patients with type 2 diabetes will be scheduled for a three-week run-in period with LR and CGM prior to participation in Part 1. Only patients with a well-functioning loop-recorder and who can comply with CGM will be included. Patients with type 2 diabetes will continue in part 2 of the study, a one year observational study employing CGM and LR and clinical examination after 1, 3, 6, 9, and 12 months and an extended observation period of 2 years employing LR and clinical examination.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with type 2 diabetes
- •Informed and written consent
- •Type 2 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
- •Treatment with insulin
- •Glycated haemoglobin A1c (HbA1c) ≤58 mmol/mol
- •One or more clinical relevant complications to diabetes defined as: peripheral neuropathy with vibration perception threshold of > 25 volt determined by biothesiometry, moderate to severe retinopathy, nephropathy (creatinine >130 μmol/l and/or albuminuria), and/or macrovascular disease. Macrovascular disease is defined as coronary disease (stable angina pectoris or previous unstable angina pectoris or myocardial infarct), cerebrovascular disease (previous stroke or transitional cerebral ischaemia), and peripheral vascular disease (previous intermittent claudication or prior acute ischemia)
- •Well-functioning LR during run-in period (acceptable readings judged by an arrhythmologist)
- •Participation in the extended study
- •Healthy individuals
- •HbA1c ≤42 mmol/mol
- •Fasting plasma glucose ≤6.1 mmol/l
排除标准
- •Patients with type 2 diabetes
- •Arrhythmia diagnosed prior to or at the time of inclusion
- •Implantable cardioverter defibrillator (ICD) or pacemaker at the time of inclusion
- •Severe heart failure (left ventricular ejection fraction <25%)
- •Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
- •Insulin naïve patients with type 2 diabetes
- •Thyroid dysfunction (except for well-regulated eltroxine substituted myxoedema)
- •Unable to comply with daily CGM during run-in period
- •Anemia (male: hemoglobin < 8.0; female: hemoglobin < 7.0 mmol/l)
- •Healthy individuals
- •Type 1 or type 2 diabetes
- •Prediabetes (HbA1c >42 mmol/l and/or fasting plasma glucose >6.1 mmol/l)
- •Family history of diabetes (type 1 og type 2 diabetes)
- •Arrhythmia diagnosed prior to or at the time of inclusion
- •ICD or pacemaker at the time of inclusion
- •Severe heart failure (left ventricular ejection fraction <25%)
- •Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
- •Thyroid dysfunction (except for well-regulated eltroxine substituted myxoedema)
- •Anemia (male: hemoglobin < 8.0; female: hemoglobin < 7.0 mmol/l)
结局指标
主要结局
Part 1: Clinically relevant arrhythmias
时间窗: 0-240 min during the combined hyper- and hypoglycaemic clamp
Composite endpoint including atrial fibrillation, brady-arrhythmias and tachy-arrhythmias. Clinically relevant brady-arrhythmias are defined as sinus arrest for more than 3 seconds, frequency below 30 beats per minute (bpm), or high grade atrioventricular (AV) block including Mobitz Type II and third-degree AV block. Clinically relevant tachy-arrhythmias are defined as sustained ventricular tachycardia (duration \>30 seconds), and non-sustained ventricular tachycardia.
Part 2: Difference in MAGE
时间窗: Within 12 months
Difference in mean amplitude of glycaemic excursions (MAGE) two hours preceding an arrhythmic event versus MAGE during non-event
Part 2: Clinically relevant arrhythmias during hypoglycaemia compared to euglycaemia
时间窗: Within 12 months
Clinically relevant arrhythmias during hypoglycaemia compared to euglycaemia
Part 2: Prevalence of clinically relevant arrhythmias as defined above
时间窗: Within 12 months
Prevalence of clinically relevant arrhythmias as defined above
次要结局
- Part 1: Differences in mean corrected QT interval (QTc)(0-240 min during the combined hyper- and hypoglycaemic clamp)
- Part 1: Difference in counter regulatory hormonal response(0-240 min during the combined hyper- and hypoglycaemic clamp)
- Part 2: Clinical relevant arrhythmias during low glucose variability compared to high glucose variability.(Within 12 months)
- Part 2: The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV(Within 12 months)
- Part 2: The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV(Within 12 months)
- Part 2: The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV(Within 12 months)
- Part 2: Correlation between plasma glucose variation and risk of clinical relevant arrhythmias(Within 12 months)
- Part 2: Correlation between prevalence and total duration of hypoglycaemia and risk of clinically relevant arrhythmias(Within 12 months)
- Part 1: Differences in haemodynamic regulation(0-240 min during the combined hyper- and hypoglycaemic clamp)
研究者
Andreas Andersen
MD, PhD-student
University Hospital, Gentofte, Copenhagen