Objective
This research has two main objectives:
• Our first objective is to find out more about the benefits for people with type 1 diabetes if they keep making their own insulin. We know that if people keep making even small amounts of insulin this helps their blood glucose and helps to reduce complications of high blood glucose. In this study we want to find out if continued insulin production has other benefits including on quality of life and costs of managing their diabetes. This is important as treatments are being developed to help preserve insulin secretion, and we need to know what the full benefits of preserving insulin secretion are likely to be to guide their use in clinical care.
• The second objective is to compare different ways of measuring a person’s own insulin secretion. This is important for the design of studies of treatments to preserve insulin secretion and for using these tests in clinical care, as C-peptide is often measured to help tell what type of diabetes a person has and to guide treatment. We want to know if simple home measurements are as good at predicting how variable blood glucose is, and hypoglycaemia, compared to the much more time-consuming hospital tests currently used. If this is the case this would make studies of new treatments to preserve insulin secretion much easier for study participants, and less costly for research funders.
An additional objective of this research is to extend a unique existing study of 755 people who were newly diagnosed with adult-onset type 1 diabetes and have been followed over 3 years from diabetes diagnosis. This study has already led to many important findings for those living with adult-onset type 1 diabetes. For example the study has shown for the first time that the symptoms and severity of type 1 diabetes in older adults, and how quickly the condition progresses, are remarkably similar to the young, however many older adults with type 1 diabetes are misdiagnosed. Collecting futher information, up to 9 years from diagnosis, will mean we can answer many additional important questions about type 1 diabetes developing in adults in the future.
Background Rationale
People with type 1 diabetes usually lose most of their own insulin secretion within a few years of diagnosis, but some people will keep making some of their own insulin for many years. We know that when people with type 1 diabetes continue to make some of their own insulin, their blood glucose is much less variable, and they have fewer occurrences of hypoglycaemia, diabetic ketoacidosis and some diabetes complications. Therefore, many researchers and research funders like Breakthrough T1D are striving to develop effective treatments to preserve insulin secretion in people with type 1 diabetes, and promising treatments have been recently identified. However, we have limited information on the benefits of retained insulin secretion beyond glucose control. For example it is possible that the much lower variability in blood glucose, and related hypoglycaemia, seen with preserved insulin secretion will improve quality of life and help the impact of type 1 diabetes on mental health. Small studies in people receiving transplants of islets (the cells that make insulin) suggest this may be the case. However this has not been examined in large studies, or in people without islet transplants, who have much lower levels of insulin secretion.
Insulin secretion is measured using a test called C-peptide. C-peptide is released when the body makes insulin, in the same amounts, but it is not present in injected insulin. Therefore by measuring C-peptide we can determine how much insulin a person makes even where they are treated with insulin injections. Studies in this area have traditionally measured C-peptide in hospital or research clinic after a liquid meal without insulin (called a mixed meal tolerance test) which takes 2-3 hours and often causes very high glucose. This needs to be undertaken repeatedly (usually every few months) in studies that are testing treatments to preserve insulin secretion, and is both expensive and often difficult for participants, making recruiting enough trial participants a challenge. Other simpler approaches have been developed, such as measurement on a fingerpick test at home, however we do not know if these tests work as well as the more complicated and expensive tests in predicting the benefits of retained insulin. In addition we do not know the best way to do these home tests, for example we could use fingerpick testing to do mixed meal tests at home in a similar way to how they are usually done in hospital, or do simpler tests after a person’s normal meals that might be performed more often, with different readings combined to get an accurate measure of how well they make insulin. When we compare these tests it is important that we don’t only compare the result of one test to the result of another, we really need to know how well different tests predict important issues for people living with type 1 diabetes, for example whether simple tests work as well as the full mixed meal test in predicting risk of hypoglycaemia.
Description of Project
This study aims to better understand the benefits of preserving insulin secretion for people living with Type 1 diabetes, and the best way to measure insulin secretion for research and clinical practice.
People living with type 1 diabetes usually lose most of their own insulin secretion soon after diagnosis, but some people keep making some insulin for many years. We know that the people who continue to make some of their own insulin have blood glucose that is much less variable, and they have fewer occurrences of hypoglycaemia and some diabetes complications. Therefore, many researchers are striving to develop effective treatments to preserve insulin secretion in people with type 1 diabetes, and promising treatments have been recently identified. However, we have limited information on the benefits of retained insulin secretion beyond glucose control. For example we do not know if the lower blood sugar variability and hypoglycaemia seen with preserved insulin secretion will reduce the impact of type 1 diabetes on quality of life and mental health.
Insulin secretion is measured using a test called C-peptide which is released when the body makes insulin. By measuring C-peptide we can determine how much insulin a person makes even where they are treated with insulin injections. Research studies have traditionally measured C-peptide in hospital or research clinic after a liquid meal without insulin (called a mixed meal test) which takes 2-3 hours and causes high glucose. This needs to be undertaken repeatedly (usually every few months) in studies of treatments to preserve insulin secretion, and is expensive and difficult for study participants. Other simpler approaches have been developed, such as measurement on a fingerpick test at home, however we do not know if these tests work as well as the more complicated and expensive tests.
In the first part of this research we will find out if continued insulin production has other benefits including on quality of life/wellbeing, mental health, and healthcare costs. To address our first aim we will use information from an existing study of 755 people newly diagnosed with type 1 diabetes as an adult, who have been followed for over 3 years with yearly measurement of C-peptide, wellbeing and other information such as use of healthcare. We will extend this study to undertake one more study visit between 5 and 10 years after diabetes diagnosis. We will then examine how loss of insulin affects a person’s wellbeing and other important outcomes over up to 10 years from diabetes diagnosis. The new information and blood samples collected will also be very important to answer other questions about adult-onset type 1 diabetes, as there are few long-term studies in this age group, especially in older adults.
In the second part of our research we will compare different ways of measuring a person’s insulin secretion. We will perform extra tests of different ways of measuring insulin secretion in 200 people living with type 1 diabetes who have a range of different insulin levels. We will compare the current ‘gold standard’ way of measuring insulin secretion, performed in a hospital or research unit, with different approaches to measuring insulin secretion at home. This includes performing the same test usually undertaken in hospital in a home setting, with C-peptide measured on a fingerpick sample. We will compare how well the different tests predict important outcomes, such as how variable the blood glucose is, or how commonly hypoglycaemia occurs.
The end result of this research will be important information on the benefits of preserving insulin secretion in adult-onset type 1 diabetes, and how we can best measure insulin secretion in clinical practice and research.
Anticipated Outcome
This research will achieve 4 outcomes:
1. We will know, for the first time, whether people living with type 1 diabetes who keep making their own insulin have better quality of life and wellbeing.
2. We will know much more detailed information about whether treatments that preserve insulin secretion in people newly diagnosed with type 1 diabetes are likely to reduce healthcare costs, for example need for appointments and hospital admissions. While we will not perform a full analysis of costs (called a health economic analysis) as part of this project we will collect the information to inform a full analysis of costs in future.
3. We will know whether we may be able to replace hospital and research site mixed meal tests, which take several hours, with C-peptide tests undertaken by people living with type 1 diabetes in their own homes. We will also know the best way to test C-peptide at home, for example though a home mixed meal test, or though using samples after a person’s normal meals.
4. We will improve a unique existing study of adults with new onset type 1 diabetes by increasing study follow up to at least 5 years after diabetes diagnosis. This will allow us to answer many other important questions about adult-onset type 1 diabetes in future.
Relevance to T1D
Knowing the wider benefits of a person living with type 1 diabetes producing their own insulin secretion, such as whether this helps their quality of life, or reduces healthcare costs, will help us know whether treatments to preserve insulin secretion (which may have side effects and are expensive) are likely to benefit people with type 1 diabetes, and help organizations that regulate and fund healthcare in deciding whether to fund these treatments. Knowing more about the benefits of retained insulin secretion will also help people with type 1 diabetes decide if they want to take these treatments. Understanding what factors are associated with reduced quality of life and/or wellbeing in diabetes may also help in reducing these issues in other ways, for example in offering targeted support.
Knowing how well different measures of insulin secretion predict better glucose control will help researchers design effective studies to test new treatments, make taking part in these studies easier and less time consuming, and may help inform how we measure insulin secretion in clinical practice for other purposes (for example for diagnosing different types of diabetes, or knowing if someone can safely stop insulin).
Extending our study of newly diagnosed adult-onset type 1 diabetes will allow us to answer many additional quesitons about type 1 diabetes in adults, particularly older adults with type 1 diabetes who have been largely excluded from similar studies in the past. For example, at present, older adults are excluded from trials of treatments to preserve insulin secretion because loss of insulin secretion is thought to be slower in this age group. Our research suggests that this is not true, and early loss of insulin remains rapid in older adults when type 1 diabetes is carefully diagnosed to exclude people with misdiagnosed type 2 diabetes (who do not lose their insulin secretion). However to date we have only been able to study insulin secretion up to 3 years from diabetes diagnosis. If we show that long term insulin secretion is similar in older adults to young adults then older adults could be included in studies of treatments to preserve insulin secretion, both allowing this age group to benefit, and making these trials much easier to recruit to.