prediction and prevention of type 1 diabetes

[Guest guest]

This article originally posted 31 May, 2012 and appeared in

<http://www.diabetesincontrol.com/topics/type-1-diabetes> Type 1 Diabetes,

<http://www.diabetesincontrol.com/topics/prevention> Prevention,

<http://www.diabetesincontrol.com/diabetes-in-control-newsletters/628> Issue

628

AACE: Prediction and Prevention of Type 1 Diabetes

Drugs aimed at halting the molecular destruction of beta cells are likely

the next step in the quest to stop the progression of autoimmune type 1

diabetes....

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Eisenbarth, MD, PhD, executive director of the Barbara Center

for Childhood Diabetes and professor of pediatrics, medicine, and immunology

at the University of Colorado at Denver School of Medicine, stated that,

" Most of the trials we do in are in recent-onset type 1 diabetes, when there

are plenty of beta cells left -- probably at least 20%.... If one could

preserve them, it would be much easier to control patients; it's like the

honeymoon phase. "

Today, autoantibody testing can predict an individual's risk of developing

autoimmune type 1 diabetes, and even the age of onset of the disorder --

information that could one day guide the use of such preventive therapy,

said Dr. Eisenbarth.

Such testing in random cadaveric donors suggests that half a million people

in the United States might be in the early stages of developing type 1

diabetes, Dr. Eisenbarth wrote in a recent paper (Endocr Pract. Published

online May 1, 2012), underscoring the urgency of finding preventive drugs.

Because the development of type 1 diabetes is a slow process, requiring

genetic predisposition and a precipitating trigger followed by the gradual

development of beta cell loss, prevention is a realistic goal.

People with genetic predispositions can develop type 1 diabetes at any stage

in life, he explained. " If one is an identical twin of someone with type 1A

diabetes, you're never out of the woods -- autoantibodies can appear later

in life and full-blown diabetes even later, " he said. A second peak in the

incidence of the disorder is seen in people 70 to 80 years of age, he added.

To date, 4 autoantibodies are implicated in the development of type 1

diabetes: the islet zinc transporter (ZnT8), insulinoma associated antigen,

glutamic acid decarboxylases, and insulin autoantibodies.

Commercial assays are available for all 4 autoantibodies, enabling the

screening of people with a family history of the disorder.

Detection of a single antibody suggests a risk of developing type 1 diabetes

of about 5%, compared with 0.3% in the general population. However, in

people with 2 or more autoantibodies, the risk is much higher -- up to a 90%

by the age of 10 in children followed from birth.

" Not only can we predict risk, now we can also predict the age at which type

1 diabetes will occur, " said Dr. Eisenbarth, explaining that there are 2

factors that predict age at onset. " If you combine these 2 parameters, you

can explain about a third of the variation in age at which type 1 diabetes

develops, " he said.

The first factor is the person's age at autoantibody detection; " that makes

sense if we think that the autoimmune process begins when that first

autoantibody appears, " he said. " Overall, the older you are when the first

autoantibody appears, the older you are when diabetes occurs. "

The second predictive factor is the level of insulin autoantibody at first

detection. " This is specific for insulin [autoantibody], " he said. " The

levels of none of the other autoantibodies correlated at all with how long

it takes to develop type 1 diabetes. "

Currently, oral insulin (to induce tolerance) and immunosuppressive or

immunomodulating drugs have been shown to preserve beta cells and to delay

diabetes onset for 6 months to 1 year. However, work by Dr. Eisenbarth's

team is directed at more specific therapies that target the trimolecular

complex: the interaction of peptides, T-cell receptors, and major

histocompatibility complex molecules.

" I bet...we're going to be able to -- in many different ways -- target this

trimolecular complex, and hopefully develop a very specific and safe

therapy, " he said. " It's unusual to have a disease that we can predict so

well, and know the autoimmunity, and not have an immunologic therapy in our

armamentarium. "

The availability of autoantibody testing for type 1 diabetes autoantibodies

is important to practicing clinicians, according to endocrinologists Shivani

Narasimhan, MD, and Parul Kakaria, MD, from the Pinnacle Health System in

burg, Pennsylvania, who attended the session. Dr. Eisenbarth's lab

" will screen family members between the ages of 2 and 45 for autoantibodies;

that is very practical to me, " said Dr. Narasimhan.

Dr. Narasimhan said that her adult patients with type 1 diabetes are " very

much concerned " about the risk of other family members and offspring

developing the disease. " If they're planning on having children or have just

had children, they want to know. " " Just because we catch it doesn't mean we

have the treatment to prevent it. "

Still, screening has other benefits, said Dr. Kakaria. " Patients can

potentially enroll in a clinical trial if they choose, they can have the

blood tests done serially, and could be followed by a pediatric

endocrinologist if they choose. "

Presented at the American Association of Clinical Endocrinologist (AACE) May

26, 2012.