Diabetes Mellitus Evaluation, Serum, at Mayo Medical Laboratories [Hot Topic]

Diabetes Mellitus Evaluation, Serum, at Mayo Medical Laboratories [Hot Topic]


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.

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