Genotype prediction of adult Type 2 diabetes from adolescence in a multiracial population

Background: Understanding the risk for type 2 diabetes (T2D) early in the life course is important for prevention. Whether genetic information improves prediction models for diabetes from adolescence into adulthood is unknown.

Methods: With the use of data from 1030 participants in the Bogalusa Heart Study aged 12 to 18 followed into middle adulthood, we built Cox models for incident T2D with risk factors assessed in adolescence (demographics, family history, physical examination, and routine biomarkers). Models with and without a 38 single-nucleotide polymorphism diabetes genotype score were compared by C statistics and continuous net reclassification improvement indices.

Results: Participant mean (± SD) age at baseline was 14.4 ± 1.6 years, and 32% were black. Ninety (8.7%) participants developed T2D over a mean 26.9 ± 5.0 years of follow-up. Genotype score significantly predicted T2D in all models. Hazard ratios ranged from 1.09 per risk allele (95% confidence interval 1.03-1.15) in the basic demographic model to 1.06 (95% confidence interval 1.00-1.13) in the full model. The addition of genotype score did not improve the discrimination of the full clinical model (C statistic 0.756 without and 0.760 with genotype score). In the full model, genotype score had weak improvement in reclassification (net reclassification improvement index 0.261).

Conclusions: Although a genotype score assessed among white and black adolescents is significantly associated with T2D in adulthood, it does not improve prediction over clinical risk factors. Genetic screening for T2D in its current state is not a useful addition to adolescents' clinical care.