Objective
More evidence and knowledge is needed to establish how best to monitor individuals at risk of type 1 diabetes to determine whether or not they are progressing towards clinical onset and identify those who may be eligible to participate in clinical trials or receive disease modifying therapies aimed at delaying or preventing progression.
This project aims to use continuous glucose monitoring to follow Australian children who have detectable islet autoantibodies to see how and when their sugar patterns start to change. This will provide more information on how type 1 diabetes develops in children, but importantly will allow researchers to identify children with early changes in their sugar patterns and invite them to participate in future type 1 diabetes intervention or prevention trials as soon as they become available in Australia. By identifying changes in their sugar patterns, this project will also enable opportunities to provide education and support to families of children who are progressing towards clinical type 1 diabetes, provide a pathway for earlier diagnosis and treatment with insulin where appropriate, whilst also helping to prevent children getting seriously sick at the time of diagnosis with diabetic ketoacidosis.
Background Rationale
There is an estimated 1.5 million children and adolescents living with type 1 diabetes around the world, and it remains one of the commonest chronic conditions of childhood. In Australia, 3 children are newly diagnosed with this lifelong, life-threatening condition on average, every day, and 1 in 3 children newly diagnosed present with diabetic ketoacidosis, a severe life-threatening medical emergency. Following diagnosis, children require daily treatment with insulin for the rest of their lives in order to survive, and the condition is associated with enormous health, psychological, social and financial burdens.
Over the past decades, researchers have made a lot of progress in understanding how type 1 diabetes develops over time. By following babies at risk of the condition, researchers have shown that you can identify children who are at greater risk of developing type 1 diabetes using a blood test that looks for proteins called islet autoantibodies, which signal that the autoimmune process which results in type 1 diabetes is happening. Researchers have also shown that in children with these antibodies, changes in blood glucose (sugar) levels start much earlier than symptoms of diabetes appear. And most excitingly, when individuals with these antibodies who had some changes in their sugar patterns, but no symptoms of type 1 diabetes, were given a drug called teplizumab in a clinical trial, the drug was shown to delay progression of their type 1 diabetes by a median of 2 years.
Teplizumab received FDA approval in November 2022 and is the first drug ever, licensed for use to delay progression to clinical type 1 diabetes. The current challenge is now how best to identify individuals who are at risk of type 1 diabetes who have some evidence of changes in their glucose metabolism, but unless they were being tested and followed would still be asymptomatic (Stage 2 type 1 diabetes) and therefore likely unaware of the disease process underway. This project aims to address this gap and generate important evidence on using continuous glucose monitoring to track and monitor individuals at risk of type 1 diabetes so that they can be offered this and emerging disease modifying therapies in the near future, at the right time and hence, have the best chance of benefiting from them.
Description of Project
There is an estimated 1.5 million children and adolescents living with type 1 diabetes around the world, and it remains one of the commonest chronic conditions of childhood. In Australia, 3 children are newly diagnosed with this lifelong, life-threatening condition (on average) every day, and 1 in 3 children newly diagnosed present with diabetic ketoacidosis, a severe life-threatening medical emergency. Following diagnosis, children require daily treatment with insulin for the rest of their lives in order to survive, and the condition is associated with enormous health, psychological, social and financial burdens.
Over the past decades, researchers have made a lot of progress in understanding how type 1 diabetes develops over time. By following babies at risk of the condition, researchers have shown that you can identify children who are at greater risk of developing type 1 diabetes using a blood test that looks for proteins called islet autoantibodies, which signal that the autoimmune process which results in type 1 diabetes is happening. Researchers have also shown that in children with these antibodies, changes in blood glucose (sugar) levels start much earlier than symptoms of diabetes appear. And most excitingly, when individuals with these antibodies who had some changes in their sugar patterns, but no symptoms of type 1 diabetes, were given a drug called teplizumab in a clinical trial, the drug was shown to delay progression of their type 1 diabetes by a median of 2 years.
This project aims to use continuous glucose monitoring to follow Australian children who have detectable islet autoantibodies to see how and when their sugar patterns start to change. This will provide more information on how type 1 diabetes develops in children, but importantly will allow researchers to identify children with early changes in their sugar patterns that mean they can be invited to participate in future type 1 diabetes intervention or prevention trials as soon as they become available in Australia. By identifying changes in their sugar patterns, this project will also enable opportunities to provide education and support to families of children who are progressing towards clinical type 1 diabetes, provide a pathway for earlier diagnosis and treatment with insulin where appropriate, whilst also helping to prevent children getting seriously sick at the time of diagnosis with diabetic ketoacidosis.
Findings from this research are expected to contribute to the global effort in the field of type 1 diabetes prevention and intervention. The research team consists of globally recognized experts and is working in close collaboration with type 1 diabetes investigators and clinicians worldwide, including JDRF supported initiatives in the US and Europe.
Anticipated Outcome
The anticipated outcomes of this project include:
1. Generating important data on using CGM, including psychosocial impacts in families and children which is needed to inform development of clinical guidelines for use of CGM in individuals with pre-symptomatic T1D. The need for clinical care guidelines for pre-symptomatic T1D is becoming increasingly urgent as screening for islet autoimmunity in both at risk, and general populations is being implemented in several countries worldwide. An evidence-based harmonized approach is vital for ensuring all children identified at risk of T1D receive the best possible clinical care and follow-up no matter where they live.
2. Identifying individuals eligible for participating in clinical trials and/or receiving disease modifying therapies according to their age and stage of T1D.
3. Enabling families with children progressing towards clinical T1D to be provided with education and support to reduce the risk of DKA at diagnosis. The role of CGM for diagnosis of Stage 3 T1D and guiding early initiation of insulin therapy remains unclear and will be essential for informing optimal management of T1D progressors and determining the influence of such early treatment on longer term glycemic outcomes in these individuals.
Relevance to T1D
There is an estimated 1.5 million children and adolescents living with type 1 diabetes around the world, and it remains one of the commonest chronic conditions of childhood. In Australia, 3 children are newly diagnosed with this lifelong, life-threatening condition on average, every day, and 1 in 3 children newly diagnosed present with diabetic ketoacidosis, a severe life-threatening medical emergency. Following diagnosis, children require daily treatment with insulin for the rest of their lives in order to survive, and the condition is associated with enormous health, psychological, social and financial burdens.
Over the past decades, researchers have made a lot of progress in understanding how type 1 diabetes develops over time. By following babies at risk of the condition, researchers have shown that you can identify children who are at greater risk of developing type 1 diabetes using a blood test that looks for proteins called islet autoantibodies, which signal that the autoimmune process which results in type 1 diabetes is happening. Researchers have also shown that in children with these antibodies, changes in blood glucose (sugar) levels start much earlier than symptoms of diabetes appear. And most excitingly, when individuals with these antibodies who had some changes in their sugar patterns, but no symptoms of type 1 diabetes, were given a drug called teplizumab in a clinical trial, the drug was shown to delay progression of their type 1 diabetes by a median of 2 years.
This project aims to use continuous glucose monitoring to follow Australian children who have detectable islet autoantibodies to see how and when their sugar patterns start to change. This will provide more information on how type 1 diabetes develops in children, but importantly will allow researchers to identify children with early changes in their sugar patterns and invite them to participate in future type 1 diabetes intervention or prevention trials as soon as they become available in Australia. By identifying changes in their sugar patterns, this project will also enable opportunities to provide education and support to families of children who are progressing towards clinical type 1 diabetes, provide a pathway for earlier diagnosis and treatment with insulin where appropriate, whilst also helping to prevent children getting seriously sick at the time of diagnosis with diabetic ketoacidosis.
Findings from this research are expected to contribute to the global effort in the field of type 1 diabetes prevention and intervention. The research team consists of globally recognized experts and is working in close collaboration with type 1 diabetes investigators and clinicians worldwide, including JDRF supported initiatives in the US and Europe.