New research presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2) reports on pilot screening programmes for type 1 diabetes from 8 different countries, and the authors – a consortium including Dr Peter Achenbach and Professor Anette-Gabriele Ziegler from the Institute of Diabetes Research, Helmholtz Munich, Munich, Germany – say that screening should be rolled out across Europe, ideally with three testing window: 2-4 years, 6-8 years and 10-15 years.*
Earlier research from these authors has established the existence of earlier presymptomatic stages of T1D, stages 1 and 2 – what was already known as the symptomatic stage is now stage 3. Early detection of type 1 diabetes (T1D) is important as preventive and disease-modifying strategies are being established (with one, teplizumab, already available and others in development), and identifying individuals in the presymptomatic stage is associated with clinical benefits, including reduced risk of diabetic ketoacidosis.
The EDENT1FI consortium is a European collaborative initiative aimed at advancing population-based screening and harmonising early detection approaches across countries, coordinated jointly by Professors Chantal Mathieu from KU Leuven, Belgium, and Anette-Gabriele Ziegler. On behalf of EDENT1FI, using a common protocol, the authors have established screening for islet autoantibodies to assess feasibility, participation rates, the prevalence of early-stage T1D, and the performance and comparability of assays across participating centres.
Sites in 8 countries participated: the Czech Republic (Prague), Denmark and Sweden (Copenhagen and Öresund Region)**, Germany (Munich, Hanover, Dresden), Italy (Milan), Poland (Warsaw, Katowice), Portugal (Lisbon, Matosinhos, Beja), and the UK (Birmingham). The screening targeted children and adolescents aged 2 to 10 years in Germany, and 2 to 17 years in other countries (due to site-specific variations in screening protocols). Screening used capillary blood for the initial test (dried blood spots in the UK) and venous blood samples for confirmation. A test for a combination of 3 autoantibodies (GADA, IA-2A, ZnT8A) was used for initial screening. Samples that tested positive were analysed for 4 autoantibodies (GADA, IA-2A, ZnT8A, and IAA) at two central laboratories (Munich, Milan). Participants with at least two autoantibodies underwent confirmatory testing; early-stage T1D was diagnosed following confirmation. Individuals with early-stage T1D were invited for education and metabolic staging (oral glucose tolerance testing and HbA1c). The study screening children with and without a first degree relative with T1D – the proportion without such a relative is obviously much higher than the proportion with one.
A total of 140,568 youth (49.2% female) participated in screening at median age of 7.6 years, including 10,273 (7.3%) with and 127,754 (90.9%) without a first-degree family history of T1D, and 2,541 not reported. Of those, 219 (2.13%, or around 1 in 45) with and 408 (0.32%, or 1 in 350) without family history had early-stage T1D. Frequencies among children without a family history ranged from 0.22% in Germany to 0.42% in the UK and 0.47% in Sweden and were associated with age (meaning that the prevalence of early-stage T1D was lowest among children in the age group of <4 years (0.22%) and increased in the age groups of 4 to <8 (0.31%) and 8 to <13 (0.40%)). In Italy, where screening took place in EASD host city of Milan, 4,507 participants with a median age of 6.5 years were screened, including 3,641 (80.8%) without a first-degree family history of T1D, of whom 5 (0.14%) had early-stage T1D. No cases of T1D were detected in the 167 Italian children with a first degree relative.
In the UK, a total of 17,409 children were screened, median age 8.4 years. Among these, 59 cases were found (0.42%) among those without a first degree relative with T1D and 67 (3.43%) with one. In Sweden, a total of 7926 children were screened, median age 9.4 years. Among these, 36 cases were found (0.47%) among those without a first degree relative with T1D and 4 (1.21%) with one. In Germany, across 43,470 children screened, median age 4.3 years, case rates were notably lower, with 90 (0.22%) in children without a first degree relative and 35 (1.36%) with one.
Of the total 634 participants with early-stage T1D, 386 (61%) completed metabolic staging: 300 (78%) had stage 1, 70 (18%) stage 2, and 16 (4.1%) stage 3 T1D. Participants with early-stage T1D are included in the European pre-T1D Registry.
The authors say: "This study shows that screening principles originally developed in Germany can be successfully applied to regions with different healthcare systems. The EDENT1FI initiative further demonstrates that screening for early-stage T1D can be effectively implemented throughout Europe."
"The next steps are aimed at integrating screening for early-stage T1D in the general population into standard medical care. In addition to Europe, there are other screening initiatives worldwide for the early detection of T1D, including in the United States and Australia."**
Italy has introduced legislation to introduce nationwide screening for T1D, but the government and regional health systems are continuing work to implement the law.
