Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study

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 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, PP = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA_1c (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.