HRs and 95% CIs of development of multiple islet autoantibodies after first appearance of any autoantibodies, development of type 1 diabetes after first appearance of any autoantibodies and development of type 1 diabetes after first appearance of multiple autoantibodies in children with the HLA DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype as calculated from Cox proportional hazard models
| Progression from any to multiple autoantibodies | Progression from any autoantibodies to type 1 diabetes | Progression from multiple autoantibodies to type 1 diabetes | ||||
| HR (95% CI) | P values | HR (95% CI) | P values | HR (95% CI) | P values | |
| Genetic risk score (per unit increase)* | 1.22 (1.07 to 1.40) | 0.003 | 1.48 (1.21 to 1.80) | 0.0001 | 1.27 (1.02 to 1.58) | 0.03 |
| HLA DR3/DR4-DQ8† | 1.11 (0.81 to 1.51) | 0.52 | 1.49 (0.94 to 2.37) | 0.09 | 1.33 (0.82 to 2.18) | 0.25 |
| Female child | 1.01 (0.77 to 1.34) | 0.92 | 1.35 (0.91 to 1.98) | 0.13 | 1.94 (1.28 to 2.93) | 0.002 |
| Age at onset of previous event (per year)‡ | 0.89 (0.83 to 0.95) | 0.0003 | 0.70 (0.60 to 0.82) | <0.0001 | 0.68 (0.58 to 0.81) | <0.0001 |
| Finland§ | 0.83 (0.59 to 1.18) | 0.31 | 1.10 (0.67 to 1.81) | 0.70 | 0.95 (0.56 to 1.63) | 0.86 |
| Germany | 0.67 (0.31 to 1.46) | 0.32 | 0.40 (0.10 to 1.67) | 0.21 | 0.39 (0.09 to 1.66) | 0.20 |
| Sweden | 0.81 (0.58 to 1.12) | 0.19 | 0.98 (0.61 to 1.57) | 0.92 | 0.99 (0.60 to 1.62) | 0.96 |
*Genetic risk score is calculated without inclusion of HLA class II genotype.
†Reference is HLA DR4-DQ8/DR4-DQ8.
‡Age at onset of the previous event (ie, of any islet autoantibodies in models 1 and 2, and of multiple islet autoantibodies in model 3); the HRs for age are reported as per 1 year increase for the sake of interpretability; however, exact age (ie, not rounded) was used in the regression models.
§Country is coded as dummy variable with USA as reference.
HLA, human leucocyte antigen.