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

Abstract

for the Fr1da Study Group 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; Յ4 indicates no to minimal depression; >20 indicates severe depression). RESULTSOf 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.

Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents

“…Effective prevention campaigns should be targeted to reach a high percentage of the general population and healthcare professionals, should be repeated and prolonged over time, and should monitor all factors influencing the occurrence of DKA [15]. Preschool screening for islet autoantibodies in the general population might be useful to prevent DKA at diagnosis, as shown in a public health screening programme among children aged 2-5 years in Bavaria, Germany, in which the prevalence of DKA at diagnosis was less than 5% [43]. Moreover, screening costs were kept low by using a relatively inexpensive and sensitive method.…”

Socioeconomic Inequalities Increase the Probability of Ketoacidosis at Diagnosis of Type 1 Diabetes: A 2014–2016 Nationwide Study of 2,679 Italian Children

“…Beyond the reports of cumulative effects of various actions, the results from this study also demonstrate the need to explore education and awareness-raising campaigns tailored to the needs of families, in particular for those with a low level of parent education and the ability to access resources and for children that are a younger age. Ideally, the frequency of DKA should be reduced to a minimum level comparable to that found in children with islet-positive autoantibodies detected by the Bavarian screening program (27), who developed overt disease. The proportion of children reporting pH value <7.30 at type 1 diabetes diagnosis was <5%.…”

Detecting Insulitis in Type 1 Diabetes with Ultrasound Phase-change Contrast Agents

“…Nanodroplet accumulation predicts disease effectively -A key goal for imaging diagnostics for T1D is to detect signatures of pre-symptomatic T1D early, where significant beta cell mass remains and thus therapeutic treatment can be most effective (2). Predicting T1D onset may also avoid complications associated with diabetic ketoacidosis (7). We detected signatures of insulitis prior to diabetes onset, where animals were euglycemic, that were absent in immunodeficient mice that did not develop diabetes.…”

“…As such there is a need to develop new methods to detect the progression if insulitis and b-cell mass decline during the pre-symptomatic phase of T1D. Furthermore, at clinical onset there is a high incidence of diabetic ketoacidosis (DKA) that can have severe health consequences (7). Thus identifying 'at risk' subjects and monitoring their underlying disease progression will also be important to mitigate the consequences of DKA.…”