1683-P: Analysis of Type 1 Diabetes Genetic Risk Score Shows 1 in 8 People with Clinically Diagnosed Adult-Onset T1D Are Misdiagnosed, and Presenting Features at Diagnosis Do Not Identify Those Misdiagnosed

Aims: Accurate initial diagnosis of adult-onset type 1 diabetes (T1D) is important. We aimed to estimate the rate of misdiagnosis in clinically-diagnosed adult T1D. We also assessed the utility of Islet autoantibodies and presenting features to identify misdiagnosed-T1D.

Methods: We used a T1D-genetic risk score (T1D-GRS) to estimate misdiagnosed-T1D in 1112 white-Europeans adults clinically-diagnosed with T1D (age diagnosis >18y) from the ADDRESS-2 study. We used 1924 gold-standard T2D as a non-T1D control. All patients were recruited <6m from diagnosis and insulin treated. We assessed clinical features and autoantibodies (GADA, IA-2A, ZNT8A) in misdiagnosed and true-T1D.

Results: People with one (n=309), two (n=285) or three (n=300) autoantibodies had a similar T1D-GRS suggesting people with ≥1 antibody positive had true-T1D (mean GRS 0.270 vs. 0.269 vs. 0.273, p=0.13). People without antibody had T1D-GRS (0.243, n=218) between true-T1D (0.271, n=894, ≥1ab+ve) and T2D (0.229, n=1924, p<0.0001) suggesting presence of non-T1D in antibody negative group. The estimated proportion of non-T1D in antibody negative group was 67% (n=146/218) which was 13% of the whole cohort (95% CI 11-15%). Misdiagnosis was higher in people diagnosed 30-75y (21%) vs. 18-30y (6%, p<0.001). Misdiagnosed-T1D and true-T1D had similar rates of polyuria (91% vs. 95%), weight loss (85% vs. 88%) and DKA (38% vs. 43%) (all p>0.05). Misdiagnosed-T1D were more likely to be male (81% vs. 59%), older (40y vs. 32y), had higher BMI (28 vs. 24) and HbA1c (105 vs. 91 mmol/mol) compared to true-T1D (all p<0.001).

Conclusion: Initial misdiagnosis of T1D is common in people diagnosed >30y (21%). When clinically-diagnosed with T1D at diagnosis, negative islet autoantibodies but not severe hyperglycaemia/DKA identify misdiagnosed people.