Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study. Issue 8 (11th February 2020) - Miller, R. G.
Abstract: Aims: To examine the association between islet autoantibody positivity and clinical characteristics, residual β‐cell function (C‐peptide) and prevalence of complications in a childhood‐onset (age <17 years), long‐duration (≥32 years) type 1 diabetes cohort. Methods: Islet autoantibodies (glutamic acid decarboxylase, insulinoma‐associated protein 2 and zinc transporter‐8 antibodies) were measured in the serum of participants who attended the 2011–2013 Pittsburgh Epidemiology of Diabetes Complications study follow‐up examination ( n =177, mean age 51 years, diabetes duration 43 years). Results: Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma‐associated protein 2, 22%; and zinc transporter‐8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P =0.03; insulinoma‐associated protein 2 antibodies, P =0.001; zinc transporter‐8 antibodies, P <0.0001). Older age at onset was also associated with an increasing number of autoantibodies ( P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA1c ( P = 0.02), insulinoma‐associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes ( P =0.02) and both distal and autonomic neuropathy ( P =0.04 for both), and zinc transporter‐8 antibody positivity was associated with higher total and LDL cholesterol ( P =0.01). No association between autoantibody positivity and C‐peptide was observed. Conclusions: The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long‐term persistence of heterogeneity in the underlying autoimmune process. What's new?: In the people with childhood‐onset (<17 years old) type 1 diabetes for >30 years in this study cohort, there was an association between older age at diabetes onset and current positivity for islet autoantibodies, as well as increasing total number of islet autoantibodies. These findings support the hypothesis of a less aggressive, but more persistent immune process in those with older age at type 1 diabetes onset. If there is long‐term persistence of heterogeneity in the autoimmune process underlying type 1 diabetes, immune intervention therapies may have potential to benefit individuals with long duration of diabetes.