Type 1 diabetes occurs when stressors (viral, physical or emotional) activate the immune system to attack insulin-producing beta cells in a person with specific genetic markup.1 It is referred to as an autoimmune condition because one's own immune system attacks its own cells. When this occurs, the body produces neutralising proteins in defence, called autoantibodies. These are markers of the body's immune activity and can be detected via a blood test.2 There are 4 main antibodies that are specific markers for type 1 diabetes: insulin (IAA), glutamic acid decarboxylase (GAD), insulinoma antigen-2 (IA2), and Zinc transporter-8 (ZnT8).3
The onset of type 1 diabetes can be classified into 4 stages:
Stage 1: 2 or more antibodies present. Normal blood glucose levels.
Stage 2: 2 or more antibodies present. Raised blood glucose but no symptoms.
Stage 3: Antibodies present. Raised blood glucose with symptoms. Usually when type 1 diabetes is diagnosed.
Stage 4: Long standing type 1 diabetes
Virtually all individuals with stage 1 type 1 diabetes (i.e. 2 or more autoantibodies present) will progress to stage 3 type 1 diabetes: approximately 35% within 5 years, 70% within 10 years, and more than 95% within 15 years.4 Given these statistics, preventative therapy is targeted at delaying the progression from stage 1 to stage 3. Interestingly, 5-10% of people with type 1 diabetes have no autoantibodies present and over time, autoantibodies that may have once been present seem to disappear.2 As a result, diagnosis can be difficult, especially considering 50% of those newly diagnosed are now adults (so it is well and truly no longer appropriate to refer to type 1 diabetes as “juvenile diabetes”).2
Teplizumab (Tzield ®) brings a new shift in type 1 diabetes management, for the first time concentrating on prevention rather than treatment. It is a medication that targets the immune system to prevent it from attacking its own pancreatic beta cells, thereby preventing the destruction of insulin producing cells and delaying progression from stage 2 to stage 3 type 1 diabetes by approximately 2 years.1 It is important to note that it does not completely prevent type 1 diabetes but rather delays time to development. First approved in December 2022 by the United States Food and Drug Administration, it is the only medication available for this indication. To be eligible for Teplizumab, one must be over 8 years of age, have at least 2 autoantibodies present and have abnormal blood glucose levels on an oral glucose tolerance test (without blood glucose levels above diagnostic range for diabetes). It is administered as a daily intravenous infusion for 14 days and costs approximately US$200,000 for the 14 day course. The most common reported side effects are rash, headache, transient low white cell count, liver enzyme derangement and nausea.5
Whilst the data from Teplizumab trials is promising in leading research around immune suppressing medications for type 1 diabetes prevention, its usefulness remains uncertain because it is only approved for use in people at high risk of type 1 diabetes, a population that is not readily recognised in the absence of regimented screening programs, especially given 90% of people living with type 1 diabetes have no family history of the condition.6
For now, the decision to screen or not is a personal one, with no incorrect choice. But bear in mind that here in Australia, Teplizumab is not yet approved by the Therapeutic Goods Administration, so cannot currently be prescribed. Whether it will be made available in the future, with a Pharmaceutical Benefits Scheme subsidy to make it affordable, remains to be seen.
The table below summarises statistics (as reported by the American Diabetes Association) to consider:
Risk of child developing type 1 diabetes* | |
Male/female without type 1 diabetes | 0.33% 1 |
Male with type 1 diabetes | 6% 7 |
Female with type 1 diabetes and child born before you were 25 | 4% 7 |
Female with type 1 diabetes and child born after you were 25 | 1% 7 |
Both parents with type 1 diabetes | 10-25% 7 |
*Note: this risk is doubled if you developed diabetes before the age of 11
Relatives of a person living with type 1 diabetes in Australia can receive autoantibody blood test screening via Type1Screen, a not for profit organisation. People with a positive test are closely monitored, promptly treated with insulin if required and have the opportunity to participate in clinical trials aimed at preventing type 1 diabetes.3 More information can be found here: https://type1screen.org/. In addition, there is a Type 1 Diabetes National Screening study currently underway to identify the most appropriate type 1 diabetes screening model for Australia. If successful, Australia may be the first country to adopt routine screening for type 1 diabetes in children, similar to the bowel, cervical and breast cancer screening programs in adults.8 We stay in the hope that high risk individuals identified through screening can one day receive treatment to prevent the development of type 1 diabetes altogether.
References
Diabetes Australia. Teplizumab (Tzield): A new drug to delay the onset of type 1 diabetes is approved in the US | Diabetes [Internet]. Diabetes Australia. 2023. Available from: https://www.diabetesaustralia.com.au/blog/tzield-teplizumab/
Subramanian S, Khan F, Hirsch IB. New advances in type 1 diabetes. BMJ [Internet]. 2024 Jan 26;e075681. Available from: https://www.bmj.com/content/384/bmj-2023-075681
Type1Screen – Screening for Type 1 diabetes [Internet]. Available from: https://type1screen.org/
Greenbaum C, Lord S, Speake C. Type 1 diabetes mellitus: Prevention and disease-modifying therapy. In: UpToDate [Internet]. Waltham: Wolters Kluwer Health; 2024. Available from:https://www.uptodate.com/contents/type-1-diabetes-mellitus-prevention-and-disease-modifying-therapy#:~:text=Teplizumab%20therapy%20%E2%80%93%20Teplizumab%2C%20a%20humanized,in%20individuals%20with%20preclinical%20disease.
Provention Bio. Tzield prescribing information. [Internet]. 2023. Available from: https://products.sanofi.us/tzield/tzield.pdf
JDRF. Facts and statistics about type 1 diabetes | JDRF Australia [Internet]. JDRF. 2024. Available from: https://jdrf.org.au/living-with-t1d/facts-figures/
American Diabetes Association. Genetics of Diabetes | ADA [Internet]. Available from: https://diabetes.org/about-diabetes/genetics-diabetes#:~:text=If%20you%20are%20a%20man,risk%20is%201%20in%20100.
Type 1 Diabetes National Screening Pilot [Internet]. Available from: https://www.kidsdiabetesscreen.com.au/