Aims/hypothesis Secondary type 1 diabetes prevention trials require selection of participants with impending diabetes. HLA-A and - B alleles have been reported to promote disease progression. We investigated whether typing for HLA-B*18 and -B*39 may complement screening for HLA-DQ8 , -DQ2 and -A*24 and autoantibodies (Abs) against islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8) for predicting rapid progression to hyperglycaemia. Methods A registry-based group of 288 persistently autoantibody-positive (Ab + ) offspring/siblings (aged 0–39 years) of known patients (Ab + against insulin, GAD, IA-2 and/or ZnT8) were typed for HLA-DQ , - A and - B and monitored from the first Ab + sample for development of diabetes within 5 years. Results Unlike HLA-B*39 , HLA-B*18 was associated with accelerated disease progression, but only in HLA-DQ2 carriers ( p  < 0.006). In contrast, HLA-A*24 promoted progression preferentially in the presence of HLA-DQ8 ( p  < 0.002). In HLA-DQ2 - and/or HLA-DQ8 -positive relatives ( n  = 246), HLA-B*18 predicted impending diabetes ( p  = 0.015) in addition to HLA-A*24 , HLA-DQ2/DQ8 and positivity for IA-2A or ZnT8A ( p  ≤ 0.004). HLA-B*18 interacted significantly with HLA-DQ2/DQ8 and HLA-A*24 in the presence of IA-2 and/or ZnT8 autoantibodies ( p  ≤ 0.009). Additional testing for HLA-B*18 and -A*24 significantly improved screening sensitivity for rapid progressors, from 38% to 53%, among relatives at high Ab-inferred risk carrying at least one genetic risk factor. Screening for HLA-B*18 increased sensitivity for progressors, from 17% to 28%, among individuals carrying ≥3 risk markers conferring >85% 5 year risk. Conclusions/interpretation These results reinforce the importance of HLA class I alleles in disease progression and quantify their added value for preparing prevention trials.