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A new study unearths new insights into the mechanisms involved in type 1 diabetes. RECSTOCKFOOTAGE/Getty Images
  • The exact mechanisms involved in the development of type 1 diabetes are still somewhat mysterious.
  • Some scientists have focused on the role of an inflammatory cytokine called chemokine ligand 2 (CCL-2).
  • However, the exact nature of the relationship between CCL-2 and type 1 diabetes is not clear.
  • A recent study adds fresh detail and may provide a new avenue toward treating or slowing the onset of type 1 diabetes.

According to the American Diabetes Association, approximately 1.6 million people in the United States have type 1 diabetes.

Type 1 diabetes is an autoimmune disease. It occurs when the immune system attacks and destroys beta cells in the pancreas. Beta cells, which produce insulin, are arranged in clusters called islets.

Although scientists have understood the autoimmune nature of type 1 diabetes for some time, it is still unclear why the immune system should turn on the pancreas.

As research continues, some researchers are looking for clues in the relationship between genes and the immune system.

New research, which appears in the Journal of Translational Autoimmunity, investigates the role of a particular gene in the risk of developing type 1 diabetes.

Scientists have already implicated a particular part of a chromosome in type 1 diabetes. However, they did not understand exactly why this region — known as locus 3p21.31 — influences risk. The current study adds more detail.

This region of the genome codes for a wide range of proteins — among them is a receptor called CCR2. When CCR2 binds with the cytokine CCL-2, it activates T cells and recruits macrophages, thereby producing inflammation.

While scientists have studied the relationship between CCL-2 and type 1 diabetes before, the results have been difficult to interpret.

Researchers agree that levels of CCL-2 differ between people with type 1 diabetes and those without the condition. However, some studies have found increased levels, whereas others have shown decreased levels.

To investigate this confusing relationship, the researchers took data from the Diabetes Autoimmunity Study in the Young (DAISY). DAISY started in 1993 and tracked 310 infants with a high risk of developing type 1 diabetes from birth.

Of these, 42 developed autoantibodies to islets but did not develop type 1 diabetes. In other words, their immune system generated a response to insulin-producing cells in the pancreas but had not yet gone on to develop type 1 diabetes. The authors refer to this group as nonprogressors.

Forty-eight of the participants did develop type 1 diabetes — the authors call this group the progressors. The researchers compared these participants with a control group of 220 people without islet antibodies or type 1 diabetes.

They found that blood levels of the cytokine CCL-2 were significantly lower in both the progressors and nonprogressors compared with the controls. As autoantibody-positive individuals progressed to develop type 1 diabetes, the scientists noted a steady decline in CCL-2 levels.

They also showed that these two groups had increased numbers of the receptor CCR2, which binds CCL-2 on their immune cells.

The authors theorize that when more receptors are available, more CCL-2 binds to these receptors. When it binds, this produces inflammation and damages the pancreas. And, because CCL-2 is bound to a receptor, levels of free-floating CCL-2 in the blood decline.

The authors conclude that inhibiting CCR2 might delay the development of type 1 diabetes in individuals with islet autoantibodies. They write:

“CCR2 inhibition could impair the recruitment of immune cells, including T cells and monocytes, to the pancreatic islet, and thus, delay the progression to islet autoimmunity.”

Dr. Faye Riley, senior research communications officer at Diabetes UK, spoke with MNT about the importance of understanding the role of genes in type 1 diabetes. She said:

“Scientists are developing type 1 diabetes risk calculators that use information from genes to identify children who have a greater chance of developing the condition at some point in their lives.”

“Right now, risk scores are being used to find people who could benefit from taking part in an immunotherapy clinical trial to delay or prevent type 1 diabetes. In [the] future — once immunotherapies become approved for use outside of a research setting — genetic risk calculators could potentially be used […] as a screening tool to identify children who would benefit from the treatment.”

“Identifying which genes are linked to type 1 diabetes gives us a way to spot those at higher risk of developing the condition,” Dr. Riley told MNT.

“Understanding more about the genetics behind type 1 diabetes could also help us better understand what triggers the condition, opening the door to new prevention strategies and treatments,” Dr. Riley said.

Although researchers conducted this study in a small sample of people, the data do seem to indicate that if CCL-2 is inhibited, it may be possible to reduce the chances of someone developing type 1 diabetes. Of course, more research is necessary before this approach reaches the clinic.