Type 1 diabetes
What is type 1 diabetes?
It is helpful to think of type 1 diabetes as a candle that burns down. If you imagine the number of insulin-producing (beta) cells that we start life with is a whole candle.
In people who are genetically susceptible to type 1 diabetes, for reasons we still don’t understand, the candle becomes alight. This is the beginning of the immune attack on the beta cells and considered stage one type 1 diabetes.
As the immune system continues to attack the beta cells, the candlestick burns down. The body is unable to manage glucose properly each time we eat, and the glucose levels start to rise. This is considered stage two type 1 diabetes.
As the candle burns down further and the beta cell loss continues, the glucose levels become consistently high. Symptoms start to appear like excessive thirst, hunger and urination, bed-wetting in children, fatigue, irritability, weight loss and blurred vision. This is when people are typically diagnosed with diabetes and is called stage three type 1 diabetes. By this stage, there is only about 20% of beta cell function remaining.
Ideally, we would extinguish the flame as early as possible in order to keep as many beta cells as possible functioning and producing insulin.
In the case of stopping the candle burning with immunotherapy treatments, the earlier we intervene, the better.
What are the possible causes of autoimmunity?
There are many! The most likely scenario is that the ‘trigger’ for the autoimmune process that leads to the body attacking the insulin producing beta cells, varies from person to person. What we do know, is that type 1 diabetes occurs as a result of genetic susceptibility and the environment. Not just the environment after birth, but even before they are born (in utero).
There has been much research around viral infections as the ‘trigger’ for autoimmunity, as well as changes in the gut microbiome (community of microbes that protect us from germs), diet (high inflammatory diets), stressful life events, low vitamin D levels and many others. Ultimately, this is an area we still don’t fully understand, but a question the ENDIA study hopes to answer. With 1400 Australian children at-risk of type 1 diabetes currently being followed from pregnancy until age 10, the ENDIA study is capturing as much information as possible about the environment from the earliest stages of life, and looking for potential associations with the development of type 1 diabetes.Is type 1 diabetes more common in people with a history of other immune diseases?
Yes it is. That being said, it is still rare to have two or more autoimmune conditions. Common autoimmune conditions that occur in combination with type 1 diabetes are Graves’ disease, Hashimoto’s disease and coeliac disease.
Why immunotherapy for the treatment of type 1 diabetes?
When we use the term ‘cure’, it often means to relieve a person of symptoms or the consequences of a disease, and there have really been two main strategies in type 1 diabetes to achieve this: replace insulin or preserve the capacity to produce it.
There have been incredible advances in restoring appropriate insulin secretion through technology, transplantation and stem cell research. However, in a person with stage 1 or even stage 2 diabetes, where functioning beta cell mass is still adequate, the aim should really be to stop the immune destruction and preserve the person’s own beta cells, or to blow out the flame and preserve the person’s own candlestick. In fact, even when the pancreas is restored through pancreatic or beta cell transplantation, we know that the autoimmune attack still needs to be addressed to maintain those functioning beta cells. The goal is to blow out the flame, stop the autoimmune attack and preserve beta cell function.
Recent research has identified immunotherapies that suppress this immune attack and preserve beta cells, delaying or decreasing the need for insulin injections. Testing new immunotherapies alone or in combination with proven ones, is a logical next step towards prevention and cure of type 1 diabetes. Each clinical trial helps us understand how to best prevent the autoimmune attack, work out who responds to immunotherapy and why they respond, and what dose is optimal.
ATIC’s vision is that every Australian with type 1 diabetes who may benefit from immunotherapy has access to achieve this.How do immunotherapies fit into the treatment landscape in type 1 diabetes? What are the downsides to insulin?
Researchers have spent many decades trying to understand the autoimmune process in type 1 diabetes. What goes ‘wrong’ in the body to trigger the attack on the insulin-producing (beta) cells in the pancreas. Further to this, the goal of autoimmune research is to understand and then apply this knowledge to find better treatment options for people with type 1 diabetes, as well as reducing the development of the complications of type 1 diabetes.
Researchers at SVI established various pathways that are critical in causing autoimmune diabetes in mice and wondered whether these pathways might also be causing type 1 diabetes in people. This led to the discovery of a medication that blocked the exact pathways that are capable of causing type 1 diabetes. This led to the BANDIT (Baricitinib in new onset type 1 diabetes) trial.
ATIC collaborators are interested in challenging insulin as the sole treatment for type 1 diabetes. Whilst insulin has been used for over 100 years to treat type 1 diabetes effectively, it is not perfect and comes with the challenges of hypoglycaemia and 24/7 monitoring to ensure sugar levels in the blood remain within safe ranges. The purpose of ATIC is to investigate treatments that might interrupt the autoimmune process and stop the attack on beta cells.
In the short term, this might mean the addition of immunotherapy medications to current treatment with insulin to reduce insulin requirements and preserve healthy beta cells. Longer term, the goal is to intervene early enough that insulin is not required at all.Why do therapies that work for other autoimmune conditions also work (or maybe work) in type 1 diabetes?
Autoimmune conditions are characterised by the immune system mistaking healthy organs like the pancreas for dangerous invading microbes such as viruses and bacteria. The general treatment strategy is to give medicines that suppress the immune system in ways that turn off the autoimmune attack without leaving the body vulnerable to outside infection.
Medications that are used to treat other autoimmune diseases like rheumatoid arthritis and multiple sclerosis are likely to work in type 1 diabetes. This is why ATIC consults rheumatoid arthritis and multiple sclerosis experts to learn from their experiences and select the best options to use in type 1 diabetes.
Beyond Insulin Seminar Series – Dr Andrew Foote, Head of Rheumatology, Northern Hospital (Melbourne)Are any ATIC experts offering "off label" immunotherapy for people with newly diagnosed type 1 diabetes?
No, not at this stage. However, immunotherapy treatment for type 1 diabetes is a fast-moving area of research. There is momentum building to bring immunotherapy treatment into clinical practice and ATIC is working closely with the type 1 diabetes community, advocates, funding bodies, and type 1 diabetes specialists locally and internationally to ensure effective treatments are brought to Australia as soon as possible.Teplizumab was recently approved in the United States by the FDA. When will it be coming to Australia?
That’s right, Teplizumab was recently shown to be effective at delaying the onset of symptomatic type 1 diabetes and the requirement for insulin injections, in people at very high risk, for up to 2 years. Teplizumab does not currently have sign off from the Therapeutic Goods Administration (TGA), so doctors in Australia cannot currently prescribe it for people at high risk of type 1 diabetes.
ATIC is working closely with the JDRF and international colleagues to bring Teplizumab to Australia and NZ in the clinical trial setting. This will be a big step towards regulatory approval of Teplizumab in Australia.Should I (my child) start taking Verapamil? I've heard it can delay type 1 diabetes.
Not necessarily. You can read more about the recent Verapamil study on our explainer page.
Why does the IAA trial use nasal insulin rather than injections?
The idea behind the use of nasal insulin is not to lower blood glucose levels. When we deliver insulin to the mucosal immune system, in this case in the nose, we are using it to educate the immune system not to attack insulin producing beta cells.
This is because it is believed the primary cause of type 1 diabetes is the immune system going to the pancreatic beta cells, recognising the insulin as foreign and attacking it. We are very hopeful, based on previous work, that by adding the nasal insulin to an immunotherapy (Abatacept), we can tolerise the immune system and turn off that immune attack.
Read more about the IAA trial.Does the availability of immunotherapy trials in Australia (versus overseas) mean that effective therapies will be available more quickly?
One of ATIC’s motivations for bringing immunotherapy clinical trials to Australia and New Zealand is to improve availability of these medications via clinical trials themselves. Ultimately, no new medication will ever reach the clinic unless it has been through the rigour of the clinical trial process.
By making immunotherapy clinical trials available in Australia and New Zealand, we are making significant contributions to the global effort to fast-track immunotherapies for type 1 diabetes. Availability of these clinical trials in Australia and New Zealand doesn’t necessarily speed up the approval process. This process remains complicated and lengthy, at least for now.
However, one of ATIC’s roles is to look at ways to speed up the regulatory approval process. The type 1 diabetes community, advocates like Diabetes Australia and JDRF will also play an important role in fast-tracking the approval process for successful immunotherapies.
Type 1 diabetes in pregnancy and gestational diabetes
Is type 1 diabetes more common in women with a history of gestational diabetes?
Gestational diabetes is more closely linked with type 2 diabetes than type 1 diabetes. Due to the hormonal changes that occur during pregnancy, the beta cells are required to produce more insulin than usual to keep the sugar levels in the blood within a safe range. One mechanism for this is because the cells become less sensitive to the body’s own insulin.
Similar to type 2 diabetes, gestational diabetes occurs when the beta cells are unable to keep up with this demand. Often, this means women with gestational diabetes need insulin injections during pregnancy to maintain healthy and safe blood glucose levels for the mother and baby.
Less commonly, someone already at risk of type 1 diabetes, whose immune system has already started to reduce their beta-cell mass, might have their diabetes “unmasked” during pregnancy because of the extra demand for insulin in pregnancy. The disease process for type 1 diabetes in these people was most likely already in progress for years prior to the pregnancy.
LADA (Latent Autoimmune Diabetes of Adults)
Do we think that LADA has a different cause than T1D?
LADA stands for Latent Autoimmune Diabetes of Adults. LADA can be thought of as a bit of a mix of type 2 diabetes and type 1 diabetes. There is an immune attack on the pancreas, but it is believed to be slower than in typical type 1 diabetes. LADA usually presents in adulthood and for this reason is often misdiagnosed as type 2 diabetes.
People with LADA eventually require insulin treatment but often patients can get by without insulin for a period of time, instead taking tablets or even managing their blood glucose levels with diet alone.Are there any clinical trials for LADA patients on the horizon?
Ultimately LADA is an autoimmune disease, but it’s slowly progressing nature means it is a difficult to run trials to show immunotherapy is an effective treatment for it.
Clinical trials are tightly restricted by time and resources. Therefore, immunotherapy trials are usually performed on people with type 1 diabetes who have just commenced insulin (newly diagnosed / stage 3) or are just about to start insulin (high risk / stage 2) because studying these groups increases the likelihood that the effect of the trial drug being tested will be captured within the limited time frame of the trial.
However, progress in the development of ways to monitor the effect of immunotherapy on the immune system, would enable trials on LADA in a shorter time frame. This is because a drug could be assessed for how effective it is based on how it reduces the attack on the beta cells, rather than needing to wait for clinical evidence (like time to starting insulin) to prove that the drug works.
Development of ways to monitor the immune system is a key focus of ATIC’s preclinical and translation domain.
Vaccines and type 1 diabetes
I was diagnosed with type 1 diabetes after receiving the covid vaccine. What is your opinion on vaccines causing type 1 diabetes?
At this stage we haven’t seen a clear association of the development of type 1 diabetes with any vaccine, including the COVID-19 vaccines. We have seen COVID-19 infection, and the stress that it places on the body unmasking diabetes. It is not uncommon for people to be diagnosed with type 1 diabetes after a viral infection, including COVID-19, but at this stage there is no evidence to suggest that vaccines trigger the immune attack that leads to type 1 diabetes.
Type 1 diabetes risk
I have type 1 diabetes (or my partner does). Are our children at higher risk of developing type 1 diabetes?
Yes, children who have an immediate family member (parent of sibling) with type 1 diabetes are at 10-15 times higher risk of developing type 1 diabetes than the general population. For reasons we don’t understand, this risk is higher when the father has type 1 diabetes, compared with the mother. Family members of someone with type 1 diabetes can now do a screening blood test at home to check whether they have the antibodies associated with type 1 diabetes. More details can be found on the Type1Screen website.
However, most people who develop type 1 diabetes do not have a relative with type 1 diabetes. The National Screening Pilot is aiming to develop a screening blood test for ALL children, to identify those with antibodies long before symptoms develop.
It is ATIC’s goal to find immunotherapy treatments that could be used to prevent children identified with early stage type 1 diabetes in these screening programs, from ever needing insulin injections.
What are the expert thoughts around type 2 diabetes medications being used for people with type 1 diabetes? Are drugs like Ozempic, Metformin or Jardiance helpful for people with type 1 diabetes?
It is important to note that at this stage, none of these medications have been approved for use in type 1 diabetes in Australia. There have been positive results in some clinical trials, particularly SGLT2 inhibitors (like Jardiance) which works by acting on the kidney to make it lose glucose (sugar) in the urine. This is really helpful because it minimises the high blood glucose levels that come after a meal. They can also lead to some weight loss due to the loss of excess calories in the urine. More recently, researchers have found that these medications also provide protection against kidney damage and heart failure in people with type 2 diabetes. However, trials are required to confirm this protection in the type 1 diabetes population.
There is also a lot of interest is the role of semaglutide (Ozempic) for type 1 diabetes. Semaglutide and a related drug called dulaglutide (Trulicity) are weekly injections that mimic a natural appetite-supressing hormone that is released from the intestine every time we eat. In type 2 diabetes, these drugs can help people lose weight, improve their glucose control and protect against kidney and heart complications. Trials are underway to determine if similar benefits are seen in people with type 1 diabetes. Some Australians with type 1 diabetes are using these injections in combination with insulin to help control appetite and improve blood glucose levels.
Page last updated: 4 April 2023