Poster 02: In people with suspected type 1 diabetes or rapid progression to insulin, a single positive islet autoantibody confirms the genetic characteristics and progression of classical type 1 diabetes

Aim: New EASD/ADA guidelines recommend testing islet autoantibodies in all clinically suspected adult-onset type 1 diabetes, including those diagnosed with type 2 diabetes rapidly progressing to insulin. We assessed whether a single positive islet autoantibody confirmed the genetic and progression characteristics of type 1 diabetes in this clinical setting.

Methods: In 1814 participants with newly diagnosed adult-onset diabetes we compared the type 1 diabetes genetic risk score (T1DGRS) and rate of loss of beta cell function (annual urine c-peptide creatinine ratio (UCPCR), over median 2 years) between definite type 1 diabetes, defined as a clinical diagnosis of type 1 diabetes and ≥2 positive islet-autoantibodies (of GAD, IA2, Znt8, n=305) and the following groups: group 1) single antibody-positive and clinical diagnosis of type 1 diabetes or uncertain and initially treated with insulin (n=199), group 2) single antibody-positive rapidly progressing to insulin (n=36).

Results: Participants with a single positive autoantibody and early insulin treatment had genetic susceptibility consistent with type 1 diabetes: T1DGRS was 0.268 (95%CI 0.264-0.272) and 0.267(0.258-0.276) for single antibody-positive participants in groups 1 and 2 respectively, 0.264(0.261-0.267) in multi-antibody positive type 1 diabetes, and 0.231(0.228-0.233) in autoantibody negative type 2 diabetes. These participants also had a rapid loss of C-peptide: annual change in UCPCR -38%(-30,-45) and -25%(-8,-39) in groups 1 and 2 respectively, in comparison to –38%(-31,-44) in multi-antibody positive type 1 diabetes, and –6%(-1,-10) in antibody-negative type 2 diabetes.

Conclusion: In people with suspected type 1 diabetes or with rapid progression to insulin, a single positive islet autoantibody confirms the genetic characteristics and progression of classical type 1 diabetes.