Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany

Abstract

Importance: Public health screening for type 1 diabetes in its presymptomatic stages may reduce disease severity and burden on a population level.

Objective: To determine the prevalence of presymptomatic type 1 diabetes in children participating in a public health screening program for islet autoantibodies and the risk for progression to clinical diabetes.

Design, setting, and participants: Screening for islet autoantibodies was offered to children aged 1.75 to 5.99 years in Bavaria, Germany, between 2015 and 2019 by primary care pediatricians during well-baby visits. Families of children with multiple islet autoantibodies (presymptomatic type 1 diabetes) were invited to participate in a program of diabetes education, metabolic staging, assessment of psychological stress associated with diagnosis, and prospective follow-up for progression to clinical diabetes until July 31, 2019.

Exposures: Measurement of islet autoantibodies.

Main outcomes and measures: The primary outcome was presymptomatic type 1 diabetes, defined by 2 or more islet autoantibodies, with categorization into stages 1 (normoglycemia), 2 (dysglycemia), or 3 (clinical) type 1 diabetes. Secondary outcomes were the frequency of diabetic ketoacidosis and parental psychological stress, assessed by the Patient Health Questionnaire-9 (range, 0-27; higher scores indicate worse depression; ≤4 indicates no to minimal depression; >20 indicates severe depression).

Results: Of 90 632 children screened (median [interquartile range {IQR}] age, 3.1 [2.1-4.2] years; 48.5% girls), 280 (0.31%; 95% CI, 0.27-0.35) had presymptomatic type 1 diabetes, including 196 (0.22%) with stage 1, 17 (0.02%) with stage 2, 26 (0.03%) with stage 3, and 41 who were not staged. After a median (IQR) follow-up of 2.4 (1.0-3.2) years, another 36 children developed stage 3 type 1 diabetes. The 3-year cumulative risk for stage 3 type 1 diabetes in the 280 children with presymptomatic type 1 diabetes was 24.9% ([95% CI, 18.5%-30.7%]; 54 cases; annualized rate, 9.0%). Two children had diabetic ketoacidosis. Median (IQR) psychological stress scores were significantly increased at the time of metabolic staging in mothers of children with presymptomatic type 1 diabetes (3 [1-7]) compared with mothers of children without islet autoantibodies (2 [1-4]) (P = .002), but declined after 12 months of follow-up (2 [0-4]) (P < .001).

Conclusions and relevance: Among children aged 2 to 5 years in Bavaria, Germany, a program of primary care-based screening showed an islet autoantibody prevalence of 0.31%. These findings may inform considerations of population-based screening of children for islet autoantibodies.

Figure 1.. Flow of Participants in a Study of the Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany

DKA indicates diabetic ketoacidosis. The control cohort was a sample of the children who did not have islet autoantibodies and were living in the Munich area.

Figure 2.. Multivariable Analysis of Relative Risks for Presymptomatic Type 1 Diabetes in a Study of the Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany

The multivariable analysis includes the variables that were significantly associated with increased relative risk for presymptomatic type 1 diabetes in unadjusted analyses (see eFigure 2 in the Supplement).

Figure 3.. Risk of Stage 3 Type 1 Diabetes in a Study of the Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany

A. The curve is truncated at 3.57 years of follow-up from screening as the number at risk reaches 15% (n = 42) of the included children. The median (interquartile range) observation time is 2.4 (1.0-3.3) years. GADA indicates glutamic acid decarboxylase autoantibody; IA-2A, islet antigen 2 autoantibody; IAA, insulin autoantibody; ZnT8A, zinc transporter 8 autoantibody.

Figure 4.. Psychological Stress Scores and Diagnosis of Presymptomatic Type 1 Diabetes in a Study of the Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany

Violin plots of Patient Health Questionnaire 9 (PHQ-9) depression scores of mothers and fathers of children with presymptomatic type 1 diabetes. Scores were assessed at the metabolic staging visit and at 6 and 12 months after diagnosis. Scores for children in the control cohort and children with symptomatic type 1 diabetes enrolled in the DiMelli study are also shown. Scores range from 0 to 27 and were interpreted as no to minimal depression if less than or equal to 4 and as severe depression if greater than 20. The violin plots display the density of PHQ-9 scores. The box plots display the median and interquartile range and extend to the upper and lower adjacent values.