Hi, I’m Matt Binnicker, the Director of Clinical Virology and Vice Chair of Practice
in the Department of Laboratory Medicine and Pathology at Mayo Clinic.
Did you know that more than 29 million Americans live with diabetes, and it remains one of
the leading causes of death in the United States?
Well, because of the significance of this disease, it’s important that we identify
patients as early as possible, and in this month’s Hot Topic, my colleague will provide
you with valuable information regarding the utility of antibody testing for the diagnosis
of type 1 diabetes.
I hope you enjoy this month’s Hot Topic, and I want to personally thank you for allowing
Mayo Medical Laboratories the opportunity to be a partner in your patients’ healthcare.
In this Hot Topic presentation, I am going to discuss the diabetes mellitus evaluation
in serum, which has been updated to include the Zinc Transporter 8 Antibody (ZnT8 Ab).
My name is Dr. Andrew McKeon.
I am a Co-Director of the Neuroimmunology Lab and Professor of Neurology, Associate
Professor of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota.
Although we are primarily a neuroimmunology lab, we also have a long-standing commitment
to serological diagnoses in type 1 diabetes.
Here are here are my disclosures.
As you view this presentation, please consider the following important points regarding antibody
testing: How is the testing going to be used in your practice?
When should the test be used?
And how will results impact patient management?
The objective of this presentation is to describe the utility of antibody testing for the diagnosis
of type 1 diabetes mellitus and to review the Mayo Clinic diabetes mellitus evaluation
of serum, including the newly added Zinc Transporter 8 Antibody.
Type 1 diabetes mellitus or type 1 diabetes accounts for most juvenile-onset diabetes
mellitus and some adult cases.
Antibodies can be detected in these patients to make a diagnosis and can even be detected
in some patients before they become symptomatic, particularly in patients who are relatives
of those with diabetes mellitus.
This testing was traditionally done by an immunofluorescence assay by looking for an
antibody binding to human pancreas, but this had relatively limited sensitivity.
Nowadays, 4 specific antigens are recognized, and antibodies targeting these antigens can
be tested for in clinical laboratories to make a diagnosis of type 1 diabetes.
These include glutamic acid decarboxylase, 65 kilodalton isoform (also known as GAD65
antibody), insulin; insulinoma-associated protein 2 or IA-2, Zinc Transporter 8.
These antibody tests have all been validated internationally as being sensitive and specific
for type 1 diabetes.
How are the antibodies detected?
Well in various labs, mainly people use either immunoprecipitation assays or ELISA assays.
At Mayo Clinic, for GAD65, insulin, and IA-2 antibodies, we use immunoprecipitation assays;
while for Zinc Transporter 8 Antibodies, we use an ELISA assay.
These antibody tests should be positive in patients with type 1 diabetes and should be
negative in patients with other diabetes type, most commonly type 2 diabetes due to insulin
resistance.
These antibodies are orderable as individual antibodies, GAD65, insulin, IA-2, Zinc Transporter
8, or as a profile where all 4 antibodies are tested for.
Now onto a little bit about utility.
These antibodies are detectable in most patients with type 1 diabetes.
At least 1 of them shall be detectable in over 90% of patients with type 1 diabetes.
Most patients have 3 or 4 of these antibodies detectable.
They can aid in the distinction of type 1 diabetes, autoimmune diabetes from type 2
diabetes.
These antibody tests can also aid in the stratification of patients with gestational diabetes for
future diabetes risk; meaning that if a woman becomes diabetic or hyperglycemic during pregnancy,
what are the chances of the patient, after pregnancy when the diabetes should resolve,
may eventually go on to develop diabetes or have persisting diabetes after pregnancy.
This testing may also aid in risk assessment in close relatives of those with type 1 diabetes.
These autoantibody tests also have utility in adults with diabetes.
Autoimmune type 1 diabetes in adults may appear like juvenile type 1 diabetes and lean patients
with rapid weight loss, but also may mimic type 2 diabetes and may be slowly progressive,
such as those with latent autoimmune diabetes of adulthood.
However, antibody-positive patients, overall, tend to be leaner than the average adult diabetic.
These patients are more likely to require insulin therapy and to require it sooner than
patients with typical type 2 diabetes and very often have a higher HbA1C at presentation.
The utility of this antibody testing in children
is very useful for distinguishing type 1 diabetes, which is the most common type, from diabetes
of other types in children.
This is particularly true in those children that are overweight, present in ketoacidosis,
and when the clinician is trying to figure out is this maturity-onset diabetes of the
young versus autoimmune type 1 diabetes.
Among pregnant patients, antibody positivity will predict future development of diabetes
outside of pregnancy; and the more antibodies that are positive, the greater the risk.
For example, if there are more than 2 antibodies positive, approximately 60% of those patients
will develop type 1 diabetes within 2 years of the pregnancy where gestational diabetes
developed.
Then also the antibody testing can be useful in trying to predict the onset of diabetes
of autoimmune type in first-degree relatives of those with autoimmune diabetes.
The more antibodies that are positive in these patients, the higher the risk of developing
type 1 diabetes within 5 years.
As you can see, this would stretch from 2% for 1 antibody positive up to about 70% for
those with 4 antibodies positive.
Just to recap on the evaluation itself, each antibody is orderable individually; but in
our comprehensive diabetes mellitus evaluation, all 4 antibodies are tested for in all circumstances.
In conclusion, serum antibody testing for type 1 diabetes can aid: distinction of autoimmune
type 1 diabetes from type 2 diabetes, prediction of future insulin needs, prediction of diabetes
after gestational diabetes, and prediction of risk for type 1 diabetes among close relatives
of patients with type 1 diabetes.
Here are some references.
Thank you very much for your attention.