Global experience in predicting type 1 diabetes. Is there experience in Argentina?

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic disease with genetic predisposition and environmental influences, appearing in early stages of life. Studies monitoring at-risk individuals with positive autoantibodies (ATC+) led to a paradigm shift in the understanding of the disease. The natural history of T1DM is now considered a continuum of presymptomatic stages, beginning with genetic risk (stages 1 and 2), which reflect the progressive autoimmune and metabolic changes that lead to the manifest disease of T1DM (stage 3). Screening for individuals with autoantibodies is part of programs for detecting children, adolescents, and adults at high risk of developing T1DM due to having a first-degree relative with T1DM or a known genetic risk based on HLA genotypes. However, more than 90% of people with newly diagnosed T1DM have no family history or known predisposing genetic markers.

The Wilson and Jungner criteria (WHO), which underpin the objectives of autoantibody screening in the general population, include: reducing the incidence of diabetic ketoacidosis (DKA) at diagnosis, decreasing healthcare costs for DKA and type 1 diabetes (T1D) treatment, access to disease-modifying therapies, and participation in clinical trials.

In Europe, several screening programs are underway: FRiDA, DiAUNION, ELSA, the Betty Study as part of EDENT1FI, INNODIA (Pan-European), BABDIAB/BABYDIET, GPPAD, UNISCREEN Italy, and TIDRA in adults. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) and the Finnish Study (DIPP) analyze genetic markers of T1D risk in newborns. TRIALNET, in the US, screens for autoantibodies (Auto ATC) in family members and now includes the general population aged 3 to 45 years. In 200,000 family members already evaluated, 5% presented at least one positive autoimmune tumor (ATC+) and approximately 2.5% had multiple positive ATC+ traits. Both the DIPP cohort in Finland and the TEDDY study screened infants with high-risk HLA haplotypes and observed that a quarter of the participants developed autoimmunity (ATC+) and more than 3% developed type 1 diabetes (T1D). The Global Platform for Autoimmune Diabetes Prevention (GPPAD) trial demonstrated that individuals with a high genetic risk for T1D had a greater than 10% probability of developing autoimmune ATC before the age of 6.

Screening methods could be integrated with newborn screening tests or pediatric primary care visits. The Fr1da study, conducted in Bavaria, Germany, screened children and showed a prevalence of 0.31% for stages 1 and 2 diabetes in preschool children from the general population. The incidence of diabetic ketoacidosis (DKA) in the screened population was significantly lower at 3.2% compared to a reference rate of 20%. The Autoimmunity Screening for Kids (ASK) program in Colorado, USA, performed autoimmunity screening (Auto-ATC) in children and adolescents aged 2 to 17 years, with a prevalence of 0.5% for early-stage type 1 diabetes (T1D). Economic models of the ASK program indicated that screening is cost-effective if DKA rates were reduced by 20% and HbA1c levels decreased by 0.1% over a lifetime.