Distinguishing between type 1 diabetes (characterised by insulin deficiency) and type 2 diabetes (characterised by insulin resistance and relative insulin deficiency) can be challenging initially. Clinical features which increase the pre-test probability of type 1 diabetes (T1DM) include a younger age of onset (age <50yrs), acute onset of symptoms, BMI <25 kg/m 2 , and a personal or family history of autoimmunity.
Anti-GAD, IA2 and ZnT8 antibodies are islet-specific, pancreatic autoantibodies which may be detectable in patients with T1DM. Anti-GAD antibodies are also found in a number of neurological conditions including stiff-person syndrome, autoimmune encephalitis and cerebellar ataxia.
The absence of autoantibodies does not rule out the possibility of T1DM. GAD antibodies are found in 70-80%, and IA2 antibodies in about 60% of paediatric patients with newly diagnosed T1DM. ZnT8 antibodies are found in approximately 35-45% of adult patients with T1DM. In addition, up to 30% of patients with the classical appearance and presentation of type 2 diabetes (T2DM) have positive autoantibodies and may have a slowly progressive type of autoimmune diabetes.
A post-prandial C-peptide test rather than diabetes related antibodies is a more useful initial test when distinguishing between the two types and should generally be ordered with the advice from an Endocrinologist. If the diagnosis remains unclear, presence of T1DM related autoantibodies can assist in clarifying, but should not be solely relied upon to achieve the diagnosis.
A reasonable strategy may be to test sequentially, starting with the most common antibodies, anti-GAD. If negative to progress to the others IA2 and progressing to anti-ZnT8 antibody testing if negative. Antibody testing for the prediction of developing T1DM is not indicated in routine practice.
References:
1 UpToDate
2 Zinc transporter 8 autoantibodies (ZnT8-ab) are associated with higher prevalence of multiple diabetes-related autoantibodies in adults with type 1 diabetes. Diabetes Res Clin Pract 2018 Dec: 146:313-320. doi: 10.1016/j.diabres.2018.11.007.
For further information contact Dr Richard Steele