medwireNews: Children at increased genetic risk for type 1 diabetes are more likely to develop the condition if they have multiple, rather than single, islet autoantibodies present at the time of seroconversion, a combined analysis of prospective cohorts shows.
Moreover, risk prediction can be further stratified by HLA-DR-DQ genotypes and age at seroconversion in people with single and multiple autoantibodies, respectively, report Vibha Anand (IBM T.J. Watson Research Center, Cambridge, Massachusetts, USA) and colleagues from the Type 1 Diabetes Intelligence (T1DI) Study Group.
Anand and team combined data from five active prospective cohorts in Finland, Germany, Sweden, and the USA, and harmonized it into four risk groups based on HLA genotype.
They then analyzed the outcomes for 16,709 infants and toddlers who were enrolled and initially tested for islet autoantibodies to insulin, islet antigen-2, and glutamic acid decarboxylase at or before 2.5 years of age.
During a median 10.4 years of follow-up, 8.5% developed at least one autoantibody that was subsequently confirmed at two or more consecutive visits (seroconversion), while 5.2% developed multiple autoantibodies and 3.9% progressed to diabetes.
Anand and team found that the risk for type 1 diabetes was higher in children who initially developed multiple versus single autoantibodies, with 15-year cumulative incidence rates of 45%, 85%, and 92%, in children with one, two, or three autoantibodies, respectively.
The corresponding positive predictive values for type 1 diabetes with one, two, or three autoantibodies were 53%, 67%, and 71%.
The researchers also found that the 15-year risk for diabetes varied significantly according to what happened in the 2 years following initial seroconversion with a single autoantibody. It was 12% among children who reverted to autoantibody negative, 30% among those who retained a single autoantibody, and 82% when the children subsequently developed multiple autoantibodies.
“These findings highlight the importance of risk evaluation based on single autoantibody versus multiple autoantibodies development at the earliest time point in the course of Islet autoimmunity development,” write Anand and co-authors in Diabetes Care.
In addition, they observed that, in children with stable single-autoantibody status, 15-year diabetes incidence was higher for those in the high-risk versus low-risk HLA-DR-DQ groups, at 40% versus 12%.
Finally, among the children with multiple autoantibodies, diabetes incidence was highest among those who developed multiple autoantibodies at or below 2 years of age, at 20 cases per 100 person–years, and decreased with increasing age quartile to six per 100 person–years in those older than 7.4 years.
Anand et al conclude: “Our findings suggest that addition of genetic markers and a repeat islet autoantibody test 2 years later may improve individual risk assessment in the single autoantibody group.”
They add: “Among those with multiple autoantibodies, the risk can be stratified by age at development of Islet autoimmunity.”
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