Type 1 Diabetes, Autoimmunity, and Teplizumab
For more than a century, Type 1 Diabetes has largely been understood through the lens of insulin. When insulin was discovered in 1921, it transformed what had previously been a fatal condition into one that could be managed. Since then, advances in insulin formulations, insulin pumps, continuous glucose monitoring (CGM), and automated insulin delivery systems have dramatically improved both survival and quality of life.
Yet despite all of these advances, insulin has never addressed the underlying cause of the diabetes itself. Blood glucose changes are the visible result, not the underlying process. Type 1 Diabetes is an autoimmune disease.
Long before the first symptoms appear, long before a diagnosis is made, and often years before insulin is needed, the immune system has already begun attacking the body’s own insulin-producing cells.
For decades, treatment has focused on replacing the insulin that is lost. Now, for the first time, medicine is beginning to explore something fundamentally different: modifying the autoimmune process itself.
The emergence of teplizumab (Tzield), recently approved in several countries including Australia and the United Kingdom, represents one of the most significant shifts in Type 1 Diabetes research and treatment since the identification of insulin itself.
Rather than replacing insulin after damage has occurred, teplizumab aims to slow the immune attack before clinical diabetes develops.
To understand how this works, we first need to understand what’s actually happening inside the body during the development of Type 1 Diabetes.
What is Autoimmunity?
The immune system exists to protect us. Every day it identifies and destroys potentially dangerous bacteria, viruses, abnormal cells, and other threats. To do this effectively, it must constantly distinguish between what belongs to the body (“self”) and what does not (“non-self”).
The immune process is remarkably sophisticated. Immune cells are trained to recognise and tolerate the body’s own tissues while remaining ready to respond to genuine threats. Multiple layers of regulation exist to prevent the immune system from mistakenly attacking healthy organs.
In autoimmune disease, however, this process breaks down; the immune system begins targeting parts of the body that it should recognise as “self”.
You could think about ++is as a highly trained security force. Normally, that security force identifies genuine intruders and removes them. In autoimmune disease, some members of the security force begin misidentifying innocent citizens as enemies.
Different autoimmune diseases target different tissues. For example, in multiple sclerosis, the immune system attacks the nervous system. In rheumatoid arthritis, it attacks the joints. In coeliac disease, it reacts to gluten and damages the small intestine.
In Type 1 Diabetes, the immune system targets the insulin-producing beta cells found within the islets of Langerhans in the pancreas.
Why Does Autoimmunity Develop?
One of the most common questions people ask is:
“What causes Type 1 Diabetes?”
This is something that I have always been intrigued by, and spent much of my early years researching and writing about the subject. More than 30 years later, we still do not know the complete story!
We are still confident that Type 1 Diabetes develops through a complex interaction between genetic susceptibility and environmental factors, which plays out differently in each individual person.
Genetics: Setting the Stage
Certain genetic variations significantly increase the risk of developing Type 1 Diabetes. Particularly important are genes within the Human Leukocyte Antigen (HLA) system, especially HLA-DR3, HLA-DR4, and HLA-DQ8.
These genes play a critical role in helping the immune system recognise proteins and determine what should or should not be attacked.
However, genetics alone do not explain Type 1 Diabetes. Many people with high-risk genetic profiles never develop the condition. Equally, many people diagnosed with Type 1 Diabetes have no known family history.
Environmental Triggers
Researchers have proposed a number of environmental factors that may contribute to the development of autoimmunity in susceptible individuals. These include:
- Viral infections, particularly enteroviruses
- Changes in the gut microbiome
- Early life environmental exposures
- Vitamin D deficiency
- Dietary factors
- Other currently unidentified environmental influences
At present, no single environmental trigger has been definitively proven to cause Type 1 Diabetes in humans. Many researchers now believe the autoimmune process evolves through a combination of influences that interact over time.
The result is an immune system that gradually loses tolerance to beta cells.
The Silent Stages of Type 1 Diabetes
One of the most important discoveries of recent decades is that type 1 diabetes does not suddenly appear. Rather, it develops progressively over many years.
Researchers now recognise three distinct stages.
| Stage | What is happening? |
|---|---|
| Stage 1 | Multiple diabetes-related autoantibodies are present, but blood glucose remains normal |
| Stage 2 | Autoantibodies remain present and blood glucose regulation begins to deteriorate |
| Stage 3 | Clinical diabetes develops with symptoms and significant insulin deficiency |
For years, and sometimes decades, the immune attack may continue silently before symptoms become obvious. By the time someone develops excessive thirst, weight loss, fatigue, or diabetic ketoacidosis, substantial beta-cell destruction has often already occurred.
Understanding the various stages has helped shape how researchers think about prevention and early intervention.
>> More on the Stages of Type1 Diabetes
Screening Family Members:
Can Type 1 Diabetes Be Detected Before Symptoms Appear?
For many years, Type 1 Diabetes was considered something that could only be diagnosed once symptoms appeared.
Today, that view is changing. Researchers now know that the autoimmune process often begins long before someone develops thirst, weight loss, fatigue, or high blood glucose levels. In many cases, diabetes-related autoantibodies can be detected years before clinical diagnosis.
This has led to increasing interest in screening people for antibodies who may be at higher risk.
Why Screen Family Members?
Although most people diagnosed with type 1 diabetes do not have a close relative with the condition, family members are still at substantially higher risk than the general population.
Brothers, sisters, children, and parents of people with type 1 diabetes are significantly more likely to develop the condition than someone without a family history. International screening programmes have therefore focused heavily on relatives of people already living with type 1 diabetes. (trialnet.org)
Screening typically involves testing for diabetes-related autoantibodies such as:
- GAD65
- IA-2
- ZnT8
- Insulin autoantibodies
The presence of multiple autoantibodies strongly predicts progression toward type 1 diabetes, even when blood glucose levels remain normal.
In fact, current international consensus statements now recognise the presence of two or more diabetes-related autoantibodies as early-stage Type 1 dDabetes, even before symptoms develop. (trialnet.org)
Why Early Detection Matters
Historically, there was an understandable question:
“If there is no way to stop Type 1 Diabetes, why would someone want to know years earlier?”
That question is becoming increasingly relevant as disease-modifying therapies emerge.
Treatments such as teplizumab are designed for people who have already entered the autoimmune stages of type 1 diabetes but who have not yet progressed to clinical disease.
Without screening, many people would never know they were in this stage.
Early identification may also help reduce the risk of severe diabetic ketoacidosis (DKA) at diagnosis, allowing families and healthcare teams to monitor changes in glucose regulation more closely and prepare for progression if it occurs.
Are Screening Programmes Available?
Several international programmes now offer autoantibody screening and monitoring for relatives of people with Type 1 Diabetes.
One of the best-known is TrialNet, an international research network studying ways to predict, delay, and prevent type 1 diabetes. TrialNet’s Pathway to Prevention programme offers screening for eligible relatives and has played a major role in advancing understanding of early-stage disease. (trialnet.org)
For New Zealand families, access pathways may evolve over time as screening initiatives, research studies, and health system priorities change. Anyone interested in screening should discuss options with their diabetes specialist team or healthcare provider and seek current information regarding available local or international programmes.
The Psychological Challenge of Knowing
Screening also raises important ethical and emotional questions.
Some families find reassurance in knowing their risk and being able to monitor changes over time.
Others may find it difficult to live with uncertainty, particularly when a positive autoantibody result does not reveal exactly when — or even whether — clinical diabetes will develop.
A positive screening result is not the same as an immediate diagnosis requiring insulin.
Instead, it identifies a person who may be travelling along the pathway toward type 1 diabetes and who may benefit from closer monitoring, research participation, or, increasingly, consideration of emerging disease-modifying therapies.
As treatments like teplizumab become available, these conversations are likely to become even more important. Detecting type 1 diabetes before symptoms appear may eventually become a routine part of diabetes prevention and early-intervention strategies rather than something reserved only for research studies.
The Immune Attack on Beta Cells
At the core of Type 1 Diabetes is a highly specific targeted immune attack against pancreatic beta cells.
Autoantibodies: The Warning Signals
One of the earliest detectable signs of autoimmune activity is the appearance of diabetes-related autoantibodies. Common examples include:
- GAD65 antibodies
- IA-2 antibodies
- ZnT8 antibodies
- Insulin autoantibodies
These antibodies are important because they act as biological markers of the disease process. However, a common misconception is that the antibodies themselves are doing most of the damage. Current evidence suggests they are better understood as warning signals rather than the primary destructive force. Their presence tells us that the immune system has recognised beta cells as a potential target.
T Cells: The Main Attack Force
The most significant beta-cell destruction appears to be carried out by immune mediator cells called T lymphocytes, or ‘T cells.’ Two major groups are involved:
CD4 helper T cells – these cells coordinate and amplify immune responses.
CD8 cytotoxic T cells – these cells directly attack and destroy targeted cells.
In Type 1 Diabetes, autoreactive T cells infiltrate pancreatic islets and progressively damage beta cells. This causes what is known as insulitis.
Under the microscope, researchers can see immune cells gathering around and within pancreatic islets, creating a local inflammatory environment that contributes to ongoing beta-cell destruction. Over time, enough beta cells are lost that the pancreas can no longer produce sufficient insulin to maintain normal glucose regulation.
Why Symptoms Often Appear Suddenly
Many people diagnosed with Type 1 Diabetes are surprised by how rapidly symptoms seem to to come on.
One week everything appears normal; then a week or two later they may be experiencing severe thirst, frequent urination, weight loss, exhaustion, or even diabetic ketoacidosis.
The autoimmune process itself is usually not sudden at all; beta-cell destruction usually occurs gradually over months or years. The reason symptoms appear abruptly is that the body can compensate remarkably well until a critical threshold is crossed. So for a long time, remaining beta cells continue producing enough insulin to maintain reasonable glucose control.
Eventually, however, insulin production falls below what the body requires. At that point glucose levels rise rapidly and symptoms become obvious. What feels like a sudden disease onset is often the visible endpoint of a much longer invisible process.
The Traditional Approach: Replacing the Missing Insulin
Since the discovery of insulin, treatment or ‘management’ has focused on managing the consequences of beta-cell loss.
Modern management may include:
- Multiple daily injections
- Insulin pumps
- Continuous glucose monitoring
- Automated insulin delivery systems
Newer formulations of insulin and modern technologies have transformed diabetes care and continue to improve outcomes. However, they do not stop the autoimmune process itself. People with Type 1 Diabetes still require insulin therapy to survive.
What if we could stop the autoimmune attack from happening?
A New Era: Immune-Modifying Therapy
Actually modifying the disease process itself has proven far more difficult. We are now entering a new era of Type 1 Diabetes intervention. And this is where teplizumab enters the story. Even so, this new class of drugs that Teplizumab belongs to is by no means represents the makings of a cure.
Teplizumab is a monoclonal antibody that targets CD3, a molecule found on T lymphocytes. It represents the first approved therapy specifically designed to alter the autoimmune process underlying Type 1 Diabetes rather than simply treating the resulting insulin deficiency.
Instead of asking, “How do we replace insulin more efficiently?” Researchers have started asking, “How do we preserve the cells that make insulin in the first place?”
So How Does Teplizumab Work?
The immune system is extraordinarily complex, and researchers are still refining their understanding of teplizumab’s effects.
Current evidence suggests the drug helps reduce the activity of autoreactive T cells involved in beta-cell destruction.
Researchers believe it may:
- Promote exhaustion of harmful beta-cell-reactive T cells
- Reduce aggressive immune responses
- Enhance regulatory immune pathways
- Help restore immune tolerance
The objective isn’t to suppress the entire immune system, but to recalibrate specific immune responses that have become misdirected.
In simple terms, teplizumab attempts to persuade parts of the immune system to stop attacking beta cells.
What does Research Data Show?
The key studies focused on individuals at Stage 2 of the Type 1 Diabetes process.
These individuals already had evidence of autoimmunity and abnormal glucose regulation but had not yet developed clinical diabetes. Compared with placebo, teplizumab significantly delayed progression to Stage 3 type 1 diabetes.
In further studies, the median time to progression was approximately doubled, with progression delayed by around two to three years on average. Some individuals experienced substantially longer delays.
This is why headlines describing teplizumab as a “breakthrough” have appeared across the United States, United Kingdom, Australia, and Europe.
However, it is equally important to understand what the drug does not do. Teplizumab does not:
- Cure type 1 diabetes
- Permanently prevent type 1 diabetes
- Restore large amounts of lost beta-cell mass
- Eliminate the need for insulin once clinical diabetes develops
It just delays progression.
So What’s the Big Deal?
At first glance, delaying diagnosis by several years may not sound revolutionary. Yet many experts consider teplizumab one of the most important developments in type 1 diabetes in decades.
The significance lies not only in the clinical effect but also in what it indicates:
That, for the first time, a therapy has demonstrated that the autoimmune process underlying Type 1 Diabetes can be modified before clinical disease develops.
That changes the conversation entirely, and gives us real hope for the future. Historically, Type 1 Diabetes treatment began after substantial beta-cell destruction had already occurred. Now, researchers are beginning to intervene earlier, and the focus is shifting from managing the condition to intervening with the disease process.
Could this represent the beginning of a completely new era in Type 1 Diabetes care?
What Comes Next?
Teplizumab is unlikely to be the final answer! Instead, many researchers view it as the first successful step into a broader future of disease-modifying therapies.
Further areas of active research include:
- Population screening programmes
- Family-member autoantibody screening
- Combination immunotherapies
- Beta-cell preservation strategies
- Regenerative therapies
- Prevention-focused interventions
The field is moving rapidly and multiple therapies may eventually be combined to produce stronger and more durable effects than any single treatment alone.
Teplizumab is not a cure. But it might be remembered in the future as the moment when Type 1 Diabetes treatment took a leap forward, beyond replacing what had been lost and started trying to preserve what remained.
Published 01 June 2026
Related Article: Teplizumab in New Zealand – a Speculative Article
| LEGAL DISCLAIMER: The information on this website is provided for general educational purposes only and is intended for a New Zealand audience. It is not a substitute for professional medical advice, diagnosis, or treatment. While I strive to ensure accuracy and relevance, please always seek guidance from your healthcare provider for personal medical decisions. Use of the content is at your own risk. Links to other sites are for convenience and do not imply endorsement. |
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