Understanding the Impact of Endogenous Insulin Secretion on Clinical Outcomes in Type 1 Diabetes and the Optimal Approach to C-peptide Measurement for Outcome Prediction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 700
- 试验地点
- 4
- 主要终点
- Capillary C-peptide measured 1-5 hours after a meal containing carbohydrates (Arm 1)
研究概览
简要总结
The purpose of this research is to understand the impact of retained endogenous insulin (as measured by C-peptide) on quality of life and related outcomes in people living with insulin treated diabetes, and, in those living with type 1 diabetes, to determine the pragmatic and non-pragmatic C-peptide measures which have the strongest association with clinical benefit (including repeated home samples and derived measures of beta cell function). The investigators will do this in two ways:
Firstly, the investigators will extend a large existing prospective study of new adult onset diabetes (Getting the Right Classification and Treatment From Diagnosis in Adults With Diabetes (StartRight)) https://clinicaltrials.gov/ct2/show/NCT03737799) which has followed 1800 participants for median 4 years from diabetes diagnosis. Participants with insulin treated diabetes will be invited to take part in a further research visit remotely or face to face. The investigators will assess the longitudinal relationship between C-peptide and the available quality of life, mental health status and healthcare utilisation measures over up to 9 years from diabetes diagnosis and assess additional measures in cross sectional analysis.
In the second part of this research, the investigators will utilise cohorts of over 2500 participants with type 1 diabetes, measured C-peptide and consent to recontact to recruit 200 participants with a range of C-peptide. Eligible participants with C-peptide measured in clinical care may also be invited to take part. The investigators will undertake detailed assessment of complex and pragmatic measures of C-peptide and beta cell function and compare performance in predicting glycaemic outcomes (using data from continuous glucose monitors) and (where relevant) patient reported outcomes.
详细描述
The purpose of this study is to understand the possible benefits of restoring insulin secretion in people living with diabetes, and to understand how insulin secretion can be best measured in people living with diabetes.
Most people living with type 1 diabetes stop making their own insulin, this means that insulin injections are needed to survive. It also means their blood glucose is variable, meaning it is very difficult to control blood glucose levels. This is in contrast to type 2 diabetes, where most people keep making their own insulin, and loss of insulin production is uncommon.
Previous research has shown that some people with type 1 diabetes keep making some of their own insulin, and this can be very helpful for their blood glucose control. However, there is limited information on long term benefits of making insulin, and other possible benefits, such as on wellbeing, have not been studied. It is important that the full benefits of making insulin are known as new treatments have been developed to preserve insulin secretion in type 1 diabetes, and/or to restore insulin secretion. These treatments are expensive and can have side effects, and have been studied only in small studies for a short amount of time. It is important to fully understand the likely long-term benefits of preserving or restoring insulin secretion to know whether healthcare providers like the NHS should fund these treatments.
At present research studies that are testing new treatments to preserve or restore a person's insulin production need to frequently test insulin secretion, using a test called a mixed meal tolerance test that needs to be undertaken in a hospital setting and takes at least 2.5 hours. This makes these studies difficult to take part in, and expensive to run. Insulin production can now be measured at home, on a finger-prick test, but more information is needed on the best way to do the home test for these kinds of studies.
This research has two parts. In the first part of this research the investigators will measure insulin secretion (using a test called C-peptide) in 500 people with insulin treated diabetes who have already taken part in a large recent study that measured their insulin secretion, and other important measures such as their quality of life and use of healthcare services, every year for up to 4 years after diabetes diagnosis. There will be assessment of participants' quality of life and other measures related to diabetes. The investigators will use this information, and the information already collected in the study, to understand the effects of retaining or loosing insulin production over up to 9 years from diabetes diagnosis, and compare whether this differs in type 1 and 2 diabetes.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Previously recruited to the StartRight study (NCT03737799) with consent to be contacted for further research
- •Clinical diagnosis of diabetes & Insulin treated
- •Able and willing to provide informed consent/assent.
- •Aged 18 years or older.
- •Inclusion Criteria:
- •Clinical diagnosis of Type 1 diabetes
- •Known C-peptide, measured as part of previous research or as part of diabetes clinical care OR Where C-peptide is not measured, participant must be within 7 years of diagnosis and have at least 1 positive islet antibody, measured at any time since diabetes diagnosis.
- •Where measured C-peptide is >600pmol/L, previous positive islet autoantibodies.
- •Able and willing to provide informed consent
- •Aged 18 years or older
排除标准
- •- Renal failure defined by eGFR <30mL/min/1.73 m²
研究组 & 干预措施
Arm 1
Adults (aged >= 18 years) diagnosed with diabetes for >3 years, treatment with insulin, and previously taken part in the StartRight study with consent to re-contact.
干预措施: Observational (Other)
Arm 2
Adults (aged >= 18 years) diagnosed with type 1 diabetes. Known level of insulin secretion, measured using a C-peptide test after diabetes diagnosis. Participants will have had C-peptide measured as part of a previous research study or as part of their diabetes clinical care. Where C-peptide is not measured, participant must be within 7 years of diagnosis and have at least 1 positive islet antibody, measured at any time since diabetes diagnosis.
干预措施: Observational (Other)
结局指标
主要结局
Capillary C-peptide measured 1-5 hours after a meal containing carbohydrates (Arm 1)
时间窗: 1 day during study participation
Analysis of Arm 1 will assess the relationship between home post-meal C-peptide (measured serially from within 12 months of diagnosis up to 10 years post-diagnosis, through extension of an existing study), and the secondary outcomes listed below. This will be assessed as longitudinal change over time (Arm 1 cohort) and cross-sectionally using the most recent visit data from the combined Arm 1 and Arm 2 cohorts.
Plasma and capillary C-peptide (Arm 2)
时间窗: 90-minutes post baseline
Primary analysis for Arm 2 will assess the relationship between home capillary C-peptide measurements (post-meal, assessed individually \& as the average of up to three measurements, and 90-minute post-mixed meal tolerance test) and 90-minute plasma C-peptide measured during a mixed meal tolerance test conducted at a research centre. Secondary analysis will compare the relationship between C-peptide measures and the continuous glucose monitoring secondary outcome listed below.
次要结局
- Questionnaire assessed hypoglycaemia and hypoglycaemia unawareness (Arm 1 & Arm 2)(Symptoms experienced during 4 weeks prior to study enrolment)
- Questionnaire assessed emotional burden (Arm 1 & Arm 2)(Symptoms experienced during 4 weeks prior to study enrolment)
- Questionnaire assessed quality of life/wellbeing (Arm 1 & Arm 2)(Symptoms experienced during 4 weeks prior to study enrolment)
- Changes/updates to diabetes treatment, complications and healthcare utilisation for relevant medical conditions since previous study visit (Arm 1)(Up to 3 years prior to study enrolment)
- Continuous glucose monitor measured glucose variability and hypoglycaemia (Arm 2)(14 days during study participation)