What is the role of islet-cell (IA2) levels in the diagnosis of type 1 diabetes mellitus (DM), and what is the ADA/EASD algorithm for the diagnosis of type 1 DM?

Updated: Oct 08, 2021
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Islet-cell (IA2), anti-GAD65, and anti-insulin autoantibodies can be present in early type 1 but not type 2 DM. Measurements of IA2 autoantibodies within 6 months of diagnosis can help differentiate between type 1 and type 2 DM. These titers decrease after 6 months. Anti-GAD65 antibodies can be present at diagnosis of type 1 DM and are persistently positive over time. (See also Type 2 Diabetes Mellitus.)

Testing for islet autoantibodies can substitute for expensive genetic testing in those patients suspected of having maturity-onset diabetes of the young (MODY). The prevalence of these antibodies is the same in patients with MODY as in the healthy population. A positive test for positive islet autoantibodies makes MODY highly unlikely. [105]

ADA/EASD draft consensus statement

A draft consensus statement released in 2021 by the ADA and the EASD provided an algorithm meant to aid in avoiding the misdiagnosis of adult-onset type 1 DM. It starts with autoantibody measurement, advising, if this does not achieve confirmation, that the patient be investigated for monogenic diabetes, with the MODY Probability Calculator and C-peptide measurement being included in the workup. If, in patients treated with insulin, the diabetes type has over 3 years after its onset still not been identified, the algorithm recommends further C-peptide measurement. This is because by then, the C-peptide level in a person with type 1 DM will probably be below 200 pmol/L. [100, 101]

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