Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes  

A guidance document, co-authored by 66 international experts including Australian researchers, has been endorsed by key diabetes organisations, including the Australian Diabetes Society (ADS). The consensus report outlines the best methods and recommendations for the frequency of monitoring progression of type 1 diabetes across pre-symptomatic stages. It also provides guidance on when insulin treatment should be introduced, for children, adults and in pregnancy. Credentialled diabetes educator Carolien Koreneff explains. 

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes 

Type 1 diabetes is usually diagnosed when high blood glucose levels cause the symptoms of hyperglycaemia, including thirst, frequent urination, fatigue and weight loss. This means that the diagnosis often ensues at a point of critical illness, requiring urgent hospital admission due to diabetic ketoacidosis (DKA), particularly in children. However, research has shown that the auto-immune condition starts well before the obvious symptoms are present.  

Screening and monitoring of type 1 diabetes will bring forward diagnoses and will make early detection a reality. To this day, there was no standard advice on how to detect, follow up or support people with, what is now referred to as, early-stage or pre-symptomatic type 1 diabetes. But this is all about to change. 

Stages of type 1 diabetes 

Previously it was thought that type 1 diabetes develops shortly before the hyperglycaemia, but years of research have shown that there are some detectable changes in people before the symptoms develop, for example in beta cell mass and insulin production. These changes can occur months or even years before the diagnosis.  

If a person is genetically susceptible, environmental factors (such as viral infections) can trigger their immune system to start attacking the pancreas. The body will produce auto-antibodies when there is such an immune attack against the beta cells. These antibodies can be detected in the blood. There are several antibodies associated with type 1 diabetes including: 

• Insulinoma-associated protein 2 autoantibody (IA-2A) 

• Insulin autoantibodies (IAA) 

• Islet cell autoantibodies (ICA) 

• Glutamic acid decarboxylase 65 autoantibody (GAD-65) 

• Zinc transporter 8 autoantibody (ZnT8) 

A person at risk of, or recently diagnosed with, type 1 diabetes will have auto-antibodies. It is estimated that people with two or more auto-antibodies have a 70% chance of developing type 1 diabetes within the next decade and nearly 100% chance of developing type 1 diabetes in their lifetime. In other words, having auto-antibodies can predict if a person will go on to develop the condition.  

The Juvenile Diabetes Research Foundation (JDRF) have described the development of type 1 diabetes in the following stages:  

No diabetes: There are plenty of beta cells (a ‘normal’ level) in the pancreas that produce enough insulin to maintain normoglycaemia. 

Triggering event causes the immune system to attack beta cells – auto-antibodies are produced and are detectable in blood tests. 

1. Two or more auto-antibodies can be found, but the person’s glucose levels remain in the ‘normal’ range. 

2. Two or more auto-antibodies can be found, and blood glucose levels have started to rise above target. 

(Both stage 1 and stage 2 are referred to as pre-symptomatic stages.) 

3. Stage 3: Two or more auto-antibodies can be found, and blood glucose levels are high as there is now significant beta cell loss. This is when the diagnosis of type 1 diabetes is made, and insulin treatment is introduced. 

4. The person has longstanding type 1 diabetes after numerous years. Two or more auto-antibodies may or may not be detected in the blood. Long-term health complications can occur. 

Although people in stages 1 and 2 don’t officially have diabetes, they are at increased risk of developing type 1 diabetes down the track. This is similar to people with pre-diabetes who are at great risk of developing type 2 diabetes over time.  

Screening for type 1 diabetes 

By detecting autoantibodies in the blood, through a simple blood test, the chance of someone going on to develop type 1 diabetes can be determined. If the chance is high, they can be monitored and it may reduce the shock of the diagnosis, at least to some degree. Perhaps more importantly, through screening, health checks, and education, the rate of developing diabetic ketoacidosis (DKA) can be reduced by 90%. 

Through research it may be possible over time to identify which environmental events are associated with the development of type 1 diabetes, and to develop preventative strategies for those who are genetically susceptible. Screening for type 1 diabetes risk can therefore also identify people who may be eligible to enter clinical trials, such as the Australian Type 1 Diabetes National Screening Pilot and the Type 1 Screen, both led by Associate Professor John Wentworth and Dr Kristine Bell, who also co-authored the guidance document. 

It is expected that, once widely implemented, screening will identify significant numbers of auto-antibody positive children and adults at risk of or living with early-stage type 1 diabetes.  

The consensus report 

JDRF, in conjunction with international experts and societies, recommend the following: 

1. Partnerships should be fostered between endocrinologists and primary-care providers to care for people who are islet autoantibody positive (IAb+).

2. When people who are IAb+ are initially identified, there is a need for confirmation using a second sample.

3. Single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals.

4. Individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support.

5. Interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies.

6. All health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. 

The guidance also emphasises “significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care”.  

The authors also state that “it is important to note that there are very limited data in adults aged 45 years and older who are IAb+” and that “this consensus document does not encompass screening for islet autoantibodies, and only provides expert clinical advice for monitoring of individuals who have screened positive for at least one islet autoantibody”. 

More information 

If you would like to read the full consensus report, please click this link.  

References: 

1. Phillip, M., Achenbach, P., Addala, A. et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetologia (2024). https://doi.org/10.1007/s00125-024-06205-5  

2. The stages of type 1 diabetes by JDRF. https://jdrf.org.au/stages-of-type-1-diabetes/ accessed 24^th July 2024