Prediction of type 1 diabetes in the general population

Abstract

Objective: To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (IA-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion.

Research design and methods: A total of 3,475 nondiabetic subjects aged 3-18 years were sampled in 1980, and 2,375 subjects (68.3%) were resampled in 1986. All subjects were observed for development of diabetes to the end of 2007. GADAs and IA-2As were analyzed in all samples obtained in 1980 and 1986.

Results: A total of 34 individuals (1.0%; 9 developed diabetes) initially had GADAs and 22 (0.6%; 9 developed diabetes) IA-2As. Seven subjects (0.2%) tested positive for both autoantibodies. The positive seroconversion rate over 6 years was 0.4% for GADAs and 0.2% for IA-2As, while the inverse seroconversion rates were 33 and 57%, respectively. Eighteen subjects (0.5%) developed type 1 diabetes after a median pre-diabetic period of 8.6 years (range 0.9-20.3). Initial positivity for GADAs and/or IA-2As had a sensitivity of 61% (95% CI 36-83) for type 1 diabetes. Combined positivity for GADAs and IA-2As had both a specificity and a positive predictive value of 100% (95% CI 59-100).

Conclusions: One-time screening for GADAs and IA-2As in the general childhood population in Finland would identify approximately 60% of those individuals who will develop type 1 diabetes over the next 27 years, and those subjects who have both autoantibodies carry an extremely high risk for diabetes. Both positive and inverse seroconversions do occur over time reflecting a dynamic process of beta-cell autoimmunity.

Figure 1

A: Probability of remaining nondiabetic in Finnish subjects initially positive (n = 34, 9 developed type 1 diabetes) or negative for GADAs (n = 3,441, 9 developed type 1 diabetes); B: positive (n = 22, 9 developed type 1 diabetes) or negative (n = 3453, 9 developed type 1 diabetes) for IA-2As; C: positive for GADAs and/or IA-2As (n = 49; 11 developed type 1 diabetes) or negative for both autoantibodies (n = 3426, 7 developed type 1 diabetes); and D: in those initially positive for two (n = 7, all developed type 1 diabetes), one (n = 42, 4 developed diabetes), or no (n = 3,426, 7 developed type 1 diabetes) antibodies.

Figure 1

A: Probability of remaining nondiabetic in Finnish subjects initially positive (n = 34, 9 developed type 1 diabetes) or negative for GADAs (n = 3,441, 9 developed type 1 diabetes); B: positive (n = 22, 9 developed type 1 diabetes) or negative (n = 3453, 9 developed type 1 diabetes) for IA-2As; C: positive for GADAs and/or IA-2As (n = 49; 11 developed type 1 diabetes) or negative for both autoantibodies (n = 3426, 7 developed type 1 diabetes); and D: in those initially positive for two (n = 7, all developed type 1 diabetes), one (n = 42, 4 developed diabetes), or no (n = 3,426, 7 developed type 1 diabetes) antibodies.