Stimulated Glucagon as a Biomarker of Hypoglycemic Risk in Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- A description of the strength and reproducibility of the relationship of post-Mixed Meal and Arginine stimulated glucagon with hypoglycaemia.
研究概览
简要总结
Type 1 diabetes (T1D) results from destruction of insulin producing beta cells by the body's own immune system (autoimmunity) causing an individual to lose the ability to make enough insulin to control their blood sugar levels and need to have insulin injections to lower blood glucose levels. Whilst high blood sugar level is a problem for people with Type 1 diabetes, taking insulin medication to lower sugar levels, delayed meals and exercise can all result in dangerously low blood sugar levels (hypoglycaemia). The biological causes of hypoglycaemia, and ways to prevent it are poorly understood. In non-diabetic individuals, a hormone called glucagon is secreted naturally to raise blood glucose levels but it is unclear why glucagon secretion is impaired during hypoglycaemia in individuals with T1D.
The aim of this prospective observational study is to test the relationship between a glucagon stimulation test and risk of hypoglycaemia in T1D. It is hoped this research will establish whether this relationship could be used as a blood test and be a clinically useful biomarker of hypoglycaemia risk and, therefore, directly inform clinical care of people with T1D, particularly those with highest risk of hypoglycaemia.
Assessment of beta cell decline has traditionally relied on timed C-peptide measures following a standardised liquid meal known as the mixed meal tolerance test (MMTT). Home finger prick blood spot C-peptide measurement might be a practical, cheap, and non-invasive alternative to a MMTT and would allow regular assessment of beta cell function over time. If proven that this sample type is a robust alternative to the gold standard MMTT venous C-peptide, it would dramatically decrease the cost and participant burden of T1D research into beta cell function.
详细描述
Blood glucose levels are normally controlled by insulin, a hormone that lowers high blood glucose levels, and glucagon which is released into the blood to raise glucose when levels are low. For people with Type 1 diabetes (T1D), taking insulin medication to lower glucose levels can sometimes result in dangerously low blood sugar levels (hypoglycaemia). The ability to release glucagon and correct blood glucose can vary, particularly in people who have had T1D for years. The study aims to find out how blood glucagon levels after a stimulus compare to a person's own experience of hypoglycaemia, and hypoglycaemia. This research will establish whether glucagon measured after a meal could be used as a blood marker of hypoglycaemia risk and help to identify individuals at high risk.
Hypothesis: Low post-mixed meal (MM) stimulated glucagon secretion predicts hypoglycaemia.
Prior to consent, all potential participants will be provided with detailed written information about the study (that complies with the UK General Data Protection Regulation (GDPR) and Data Protection Act 2018) and an opportunity to discuss it with one of the research team. All participants will be informed of their right to withdraw from the study at any time without prejudice or jeopardy to any future clinical care.
A unique study ID will be allocated to the participant to link all participant study information and samples. The participant's clinical characteristics and sample results will be recorded on the participant's Case Report Form and entered on the study database.
All participants will undergo core data collection, measurements and provide fasted and stimulated blood samples via a cannula at the baseline MMTT and AST visits 1 and 2 and again at the 6 months 'Light MMTT' / repeat AST visit. The order of MMTT and AST tests in visits 1 and 2 will be randomised to check for an order effect. Test choice for Visit 3 depends on the peak glucagon results from Visits 1 and 2. At Visits 1 and 3, participants will be asked to complete the hypoglycaemia questionnaire data (Clarke and Gold scores) to assess awareness of hypoglycaemia and quality of life measures which may relate to the MM-glucagon. Participants will be given an Abbot FreeStyle Libre Pro continuous blood glucose monitor (CGM) and asked to perform a 2-week continuous measure of blood glucose (CGM). Clinical diabetes care will not be changed and participants with T1D will use their own insulin regimes and self-monitoring (even if CGM or Abbot FreeStyle Libre Pro) during the study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of Type 1 diabetes
- •Insulin treated
- •Known urine C-peptide status (using Urinary C-Peptide Creatinine Ratio [UCPCR], positive/negative defined by UCPCR 0.2nmol/mmol cut-off)
- •Age 16-65 years inclusive
- •Able and willing to provide informed consent/assent.
排除标准
- •Age less than 16 year or over 65 years
- •Pregnant or lactating (as this may limit blood sampling and affect T cell function)
- •Any medical condition that, in the opinion of the investigator, would affect the safety of the subject's participation, or validity of results.
结局指标
主要结局
A description of the strength and reproducibility of the relationship of post-Mixed Meal and Arginine stimulated glucagon with hypoglycaemia.
时间窗: 22 months
The longitudinal stability of stimulated glucagon will be described, including its relationship with variation in hypoglycaemia frequency, and the potential to predict future hypoglycaemia. This will be be determined from post-MM \& Arginine-induced plasma glucagon levels, continuous glucose monitoring (CGM) time spent in hypoglycaemia, and self-reported hypoglycaemia episodes, hypoglycaemia fear/awareness, and fear of hypoglycaemia.
次要结局
- The relationship between plasma glucagon levels under basal conditions, following a stimulation (by mixed meal or arginine)(22 months)
- Longitudinal variability of glucagon levels and its relationship to episodes of hypoglycaemia in long-duration T1D.(22 months)
- Home finger prick blood spot C-peptide measurement is a practical alternative to MMTT(22 months)