Autoantibody order, timing predict genetically at-risk youngsters probably to get kind 1 diabetes

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Children with multiple islet autoantibodies – biological markers of autoimmunity – are more likely to develop symptomatic type 1 diabetes (T1D) than children who remain positive for a single autoantibody.

New findings from the TEDDY (Environmental Determinants of Diabetes in the Young) study in the US and Europe now show that detailed information about the order, timing and type of autoantibodies that appear after the first autoantibody is predicting, Which children are most likely to improve significantly can develop type 1 diabetes more quickly.

The TEDDY analysis was published in the September 2020 issue of Diabetes Care.

“A better understanding of the different spreads of autoantibodies is important because it enables us to identify children at risk earlier in the disease process,” said lead author of the study, Kendra Vehik, Ph.D., Professor of Epidemiology at the University of South Florida Health (USF Health) Institute of Health Informatics at Morsani College of Medicine. “That said, while children are still asymptomatic, we can begin exploring interventions and strategies that can reduce, delay, or stop the progression of type 1 diabetes.”

While antibodies are molecules that are produced by the body’s immune system to recognize and destroy certain viruses, bacteria, and other harmful substances, autoantibodies are antibodies that target a person’s own healthy tissues. In the case of T1D, a misdirected autoimmune reaction attacks the pancreas and gradually destroys the organ’s insulin-producing beta cells.

Without the hormone insulin, the body cannot regulate blood sugar levels, which can lead to serious, long-term medical complications such as cardiovascular disease, nerve and kidney damage, and loss of vision. Children (and adults) with T1D need to monitor their food intake and exercise, and take daily insulin injections or use an insulin pump to check their blood sugar levels.

“Physically and mentally it is a very distressing illness that needs to be treated every day for a lifetime,” said Dr. Vehemence.

For this TEDDY analysis, eligible children with an increased genetic risk for T1D were examined every three months from the age of 3 months up to 15 years for the development of an autoantibody against pancreatic insulin-producing cells: glutamic acid decarboxylase antibodies (GADA) , Insulin autoantibodies (IAA) or insulinoma-associated protein-2 autoantibodies (IA2-2A). The researchers also looked for the later appearance of a second autoantibody and further progression to T1D. The autoantibody of zinc transporter 8 (ZnT8A) was only measured in children who developed an IAA, GADA or IA-2A. These four different autoantibodies are so far the most reliable biological indicators of early T1D before symptoms appear.

Of the 608 study participants – all tested positive for a first-time IAA or GADA – more than half (336) developed a second autoantibody. In addition, 53% of these 336 children with a second antibody developed T1D within approximately 3.5 years. Only about 10% of the 272 children who tested positive for a single autoantibody at the end of this study’s follow-up (December 31, 2019) had switched to T1D.

The most important study results:

  • All study participants had genotypes at high risk for T1D. However, children at increased risk who also had parents or siblings with T1D were more likely to develop a second autoantibody than children without a family history.
  • The younger the child was when they tested positive for a first autoantibody, the greater the risk of developing a second autoantibody. Conversely, the risk of T1D decreased when the first autoantibody appeared when the child was older.
  • Children who tested positive for a second autoantibody, regardless of type, had at least a five-fold increased risk of developing T1D compared to children who remained positive for a single autoantibody. IA-2A as the second autoantibody conferred the highest risk compared to GADA, IAA or ZnT8A.
  • The risk of progression to T1D was influenced by how quickly the second autoantibody appeared. The appearance of a second autoantibody within a year of the first doubled the risk of progression to T1D. The likelihood of children developing T1D decreased as the months between the first and second autoantibody appearances increased.

Better stratification of risk of progression from the onset of autoimmunity to symptomatic disease could help diagnose T1D earlier and provides an opportunity to prevent diabetic ketoacidosis (DKA) and its serious complications by educating parents to watch out for early signs said Dr. Vehemence.

“For example, if a clinician knows that a young child who tests positive for IA-2A, the second autoantibody to appear, is at a higher risk of developing type 1 diabetes more quickly, they may reduce the risk of symptomatic onset of the disease . ” Doctors can also educate parents about the early signs of illness, such as weight loss, extreme thirst, frequent urination, or other DKA symptoms, “she said.” In this case, parents know that they should see a doctor or their child as soon as possible Should bring hospital. “

Specific antibody risk profiles can also help identify those children at risk who are most likely to benefit from recruiting for T1D prevention studies, added Dr. Vehicle added.

Dr. Vehik next plans to build on a previous TEDDY study linking viral behavior to T1D diabetes to test whether persistent viral infections are environmentally responsible for the transition from first- to second-dissolving islet autoantibodies in children who are genetically prone to diabetes can trigger.

T1DM risk in children with autoantibody reversion

More information:
Kendra Vehik et al., Hierarchical Order of Spread of Certain Autoantibodies and Progression to Type 1 Diabetes in the TEDDY Study, Diabetes Care (2020). DOI: 10.2337 / dc19-2547 Provided by the University of South Florida

Quote: Autoantibody Order, Timing Predict Genetically Vulnerable Children Most Likely to Get Type 1 Diabetes (2020, October 29), accessed October 29, 2020 from genetically-at-risk -children-diabetes.html

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