Type 1 diabetes starts long before symptoms appear
Carolien Koreneff, Registered Nurse and Credentialled Diabetes Educator, attended the Australian Diabetes Congress in Melbourne in August 2026, which brought together more than 3,000 delegates from around the world. One of the topics that stood out was the growing recognition of the stages of type 1 diabetes. Here, she explains the latest research.
When someone is diagnosed with type 1 diabetes, we tend to assume the condition developed only in the weeks leading up to diagnosis. In reality, type 1 diabetes often begins many years before the familiar 4T symptoms (tired, toilet, thirsty, and thin) appear. By the time symptoms develop, the autoimmune process that causes type 1 diabetes has typically been progressing silently in the background for years.
Type 1 diabetes is an autoimmune condition in which T-cells gradually attack and destroy the insulin-producing beta cells in the pancreas. During the process, the body produces antibodies that can be detected in the blood. These antibodies do not damage the pancreas themselves, but act as markers that the autoimmune process is underway. At this stage, a person feels well and has no symptoms, even though type 1 diabetes may already be developing in the background.
Stages of type 1 diabetes
We now know that there are three stages of type 1 diabetes.
Stage 1: The beginning of the autoimmune process where the glucose levels remain in the normal range, but two or more antibodies are present
Stage 2: By now enough of the beta cells are destroyed to cause dysglycaemia (elevated glucose levels), but insulin treatment is not needed yet and no overt symptoms of hyperglycaemia are present
Stage 3: Type 1 diabetes is diagnosed when hyperglycaemia (high blood glucose level) is significant, with overt symptoms, and insulin treatment is needed
Some health professionals mention a 4th stage of type 1 diabetes:
Stage 4 is long-standing type 1 diabetes where all the beta cells are destroyed. This is usually indicated by low or undetectable C-peptide levels and insulin dependence.
How quickly a person moves from Stage 1, through Stage 2, to Stage 3 will vary quite widely but, if antibodies are present, it is quite likely that the individual will eventually develop type 1 diabetes. Broadly speaking it takes around 5-8 years to move from Stage 1 to Stage 2, and around 2-5 years to move from Stage 2 to Stage 3.
If only one positive antibody is detected, it is estimated that there is around a 20% chance of ever needing insulin. If two or more antibodies are present it is important the individual has regular follow ups, as they are more likely to progress to type 1 diabetes.
Research suggests that the younger the person is, the quicker they seem to progress through the stages. In children, insulin production in children can drop around 50% in two years (during Stage 3 type 1 diabetes), compared with a decline of around 20-25% drop in adults over the same period.
Why is early detection important?
Early detection can help shift the diagnosis from taking place as a medical crisis towards a more planned transition care.
If we can detect type 1 diabetes in earlier stages, we can:
- Build more supportive networks and prepare through education and counselling
- Reduce uncertainty and help individuals and families feel more informed, prepared, and confident in managing future challenges
- Implement a monitoring plan
- Allow for individual enrolment in clinical trials aimed at preventing disease progression or approved treatment
- Reduced rates of diabetic keto-acidosis (DKA, a life-threatening medical condition)
- Avoidance of hospitalisation
- Decreased insulin requirements
- Reduced median HbA1c level
Why is delaying type 1 diabetes important?
If the progression of type 1 diabetes can be slowed, a person may be able to remain in the earlier stages of the condition for longer before needing insulin treatment.
This may:
- Delay the need for insulin injections and hence reduce the risk of hypoglycaemia
- Delay the need for regular glucose monitoring
- Reduce the risk of DKA and other acute complications
- Likely reduce the risk of future chronic complications
- Allow more time for education, planning, and support
- Help maintain quality of life and wellbeing
Early intervention strategies
Over the past several decades, numerous prevention and intervention studies have been conducted in people with Stage 1 and Stage 2 type 1 diabetes, including large, well-designed placebo-controlled clinical trials.
Several therapies are now in late-stage development and have demonstrated the ability to preserve beta-cell function in people with newly diagnosed Stage 3 type 1 diabetes.
In addition, teplizumab is now available in some countries for people aged 8 years and older with Stage 2 type 1 diabetes and has been shown to delay progression to Stage 3 disease.
We also have the following tools available to monitor progression:
- Self-monitoring of blood glucose (via finger prick)
- Random plasma glucose levels
- C-peptide levels
- Oral Glucose Tolerance Tests (OGTT)
- HbA1c
- Continuous Glucose Monitoring
- Auto-antibody monitoring
C-Peptide
When the body makes the molecule insulin it makes pro-insulin, which is insulin combined with C-peptide. C-peptide on its own does not do much, it seems to mainly stabilise the insulin in transit from the pancreas to other parts of the body.
C-peptide reflects the body’s own insulin production and is the preferred way to assess how much beta-cell function remains. This is because C-peptide is not cleared by the liver and has a longer half-life than insulin (20-30 minutes rather than 3-5 minutes) but is produced by our bodies at the same rate.
Injected insulin does not have C-peptide, so if we find C-peptide in someone’s blood it is linked to insulin from their own body; in other words, it is a way of measuring endogenous insulin production.
You could think of having at least some residual endogenous insulin production as ‘power-assisted steering’, it makes life a lot easier, with less effort.
Monitoring C-peptide levels
Monitoring C-peptide levels can be a useful tool as C-peptide is a surrogate measure of beta cell function.
How much C-peptide we need to be present, for our bodies to function properly and unassisted, varies depending on whether you are fasting or stimulated (after a glucose load), and whether or not you have any insulin resistance.
Measuring C-peptide levels has not been used a lot traditionally. If it was used, it was mainly to distinguish between type 1 and type 2 diabetes, between type 1 diabetes and MODY (Maturity Onset Diabetes in Youth), and in some case to detect insulinomas in people with hypoglycaemia.
But we can now also use the C-peptide measure to monitor beta-cell preservation, and/or monitor beta-cell replacement therapy (islet and pancreas transplantation).
Clinical data supports the importance of maintaining beta-cell function in people with type 1 diabetes. Individuals with residual beta-cell function in long-standing Stage 4 type 1 diabetes, as indicated by the presence of C-peptide, are associated with a better clinical trajectory.
Interpreting C-peptide levels in early phase type 1 diabetes
Why is C-peptide harder to interpret in early-stage type 1 diabetes?
C-peptide is a marker of the body’s natural insulin production and is the preferred way to assess how much beta-cell function remains. Hence, in Stage 3 type 1 diabetes, it is relatively straight forward to use C-peptide levels for diagnosis.
But when it comes to monitoring C-peptide in the early stages of type 1 diabetes we see paradoxical changes. C-peptide levels seem to initially increase as glucose levels rise, once a person gets closer to the diagnosis. It appears that, for most people, the remaining beta cells overcompensate by producing more insulin in response to a glucose load.
It is important to also note that Insulin sensitivity and glucose responses vary between individuals. Hence C-peptide may underestimate or overestimate true beta-cell function and therefore C-peptide should be interpreted alongside other measures of disease progression.
Other reasons for the paradoxical changes in C-peptide in early-stage type 1 diabetes include:
- Failure to distinguish first and second-phase insulin secretion – as the first phase declines and insulin secretion is delayed into the second phase, there can be an underestimation of beta cell function/ability to manage blood glucose
- Glucose changes during the test – do not account for lesser glucose stimulus due to less glucose rise, underestimating beta-cell function in early-Stage type 1 diabetes
- Insulin sensitivity – affects the relationship between glucose and insulin/C-peptide and may change over time in the same individual (e.g. puberty)
- Glucotoxicity – rate of disease progression and loss of beta-cell function may be overestimated in Stage 2 type 1 diabetes
- Insulin secretory effect of non-glucose components in diet (e.g. amino acids) – ability of beta-cell function to control blood glucose in normal diet underestimated
Maintenance of residual beta-cell function
Preserving residual beta-cell function
In Stage 3 type 1 diabetes, preserving residual beta-cell function, as measured by C-peptide levels, is associated with a range of clinical benefits, including:
- Improved glucose management
- Lower insulin requirements
- Reduced risk of diabetic ketoacidosis (DKA)
- Fewer hospitalisations
- Reduced risk of severe hypoglycaemia
- Lower risk of long-term diabetes complications
CGM for predicting progression
People with Stage 1 or Stage 2 type 1 diabetes do not need daily monitoring of glucose levels, although CGM from time-to-time may be useful in seeing how they are progressing.
The Autoimmunity Screening for Kids (ASK) study found that those who spent 10% of time with glucose levels above 7.8mmol/L had an 80% risk of progressing to Stage 3 type 1 diabetes over 1 year. In comparison, those with <10% CGM time spent >7.8mmol/L had a risk progression of just 5% over 12 months.
The Trialnet Pathway to Prevention study similarly showed that CGM can help predict progression to insulin requirements, but it is not a perfect measure.
The current professional opinion internationally is that CGM can be integrated into routine surveillance of antibody positive individuals. This is as CGM provides real-time insights into lifestyle effects on glucose, which may enable informed self-management and clinic decisions. However, current stage definitions are not CGM-based; staging relies on autoantibodies and glycaemia (OGTT/HbA1c). Therefore, oral glucose tolerance tests remain the gold standard for staging, at least for now.
Key take-home messages
- Type 1 diabetes begins long before symptoms appear
- C-peptide is the best available marker of residual beta-cell function
- Preserving beta-cell function provides significant clinical benefits
- Current staging is based on autoantibodies and glycaemia, not CGM
- Disease-modifying therapies are shifting the focus from treating type 1 diabetes to intervening earlier in the disease process
By Carolien Koreneff, Registered Nurse and Credentialled Diabetes Educator
References:
Presentation by Prof Colin Dayan (University College, Oxford, UK) at the Australasian Diabetes and Technology Summit (ADATS), 18 August 2026, Melbourne Convention and Exhibition Centre, From Biomarkers to Intervention: Using C-Peptide and CGM in Early-Stage Type 1 Diabetes.