Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study

Abstract

Introduction: Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care.

Methods and analysis: Children aged 2-5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed.

Results: Of the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies.

Discussion: Staging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education.

Ethics dissemination: The study was approved by the ethics committee of Technische Universität München (Nr. 70/14).

Keywords: childhood; islet autoantibodies; screening; type 1 diabetes.

Figure 1

Study design. GADA, glutamic acid decarboxylase autoantibodies; IAA, insulin autoantibodies; IA-2A Insulinoma-associated antigen 2 autoantibodies; RBA, radiobinding assay; ZnT8A, zinc transporter eight autoantibodies.

Figure 2

Numbers of children who underwent the islet autoantibody screening per week between February and November 2015.

Figure 3

(A) Participation rates of primary care paediatricians per region in Bavaria (blue) and the mean number of children screened per primary care paediatrician (red). (B) Affiliated paediatric diabetes centre in Bavaria (black squares) following the children diagnosed with pre-type 1 diabetes. Children and families are offered an education and counselling programme following the diagnosis of pre-type 1 diabetes, glycaemic staging and psychological care related to the early diagnosis of diabetes.

Figure 4

Correlation between capillary and venous blood levels of antibodies against GAD, IA-2, and ZnT8 in 31 children (GADA: R² 0.69, p<0.0001; IA-2A R² 0.98, p<0.0001; ZnT8RA: R² 0.89, p<0.0001). GAD, glutamic acid decarboxylase; GADA, glutamic acid decarboxylase autoantibodies.

Figure 5

Cumulative frequency distribution of RBA values for islet autoantibody measurements in capillary blood samples. For each islet autoantibody, RBA values (x axis) are plotted against the percentage of samples having equal or lower values (y axis). Shown are samples that were <97.5 centile in 3-Screen ELISA (solid lines; n=409) and samples that were >97.5 centile in 3-Screen ELISA (broken lines, n=568). For IAA, the distributions are shown for samples that were visibly haemolysed (red lines) and non-haemolysed (black). The dotted lines represent the thresholds of positivity established for venous blood.