Screening of pre-type 1 diabetes in high-risk paediatric population: a pilot study in Latvia

The incidence of type 1 diabetes (T1D) among the paediatric population in Latvia is gradually increasing, and ~ 50% of patients with newly diagnosed T1D present with diabetic ketoacidosis (DKA). This study aimed to initiate T1D screening for high-risk children to reduce the rate of DKA and enable early pre-symptomatic intervention. This prospective observational study was conducted at Children's Clinical University Hospital (CCUH) from March 2024 to February 2026. Siblings aged 2-17 years of patients with T1D were invited to participate. The parents completed a short questionnaire regarding participants' health status and family history. Screening was performed in two stages: (1) 3-screen ELISA and insulin autoantibody (IAA) ELISA testing; if ≥ 1 positive then (2) ELISA testing for all four autoantibodies (AAs) separately: IAA, insulinoma-associated antigen-2 (IA-2A), zinc transporter 8 (ZnT8A) and glutamic acid decarboxylase 65 (GAD-65A) antibodies, glycaemic status assessment, and screening for celiac disease and autoimmune thyroiditis. Participants with ≥ 2 AAs in the second screening underwent a 2 h-oral glucose tolerance test (OGTT). Parents of participating children were screened for anxiety and depression using GAD-7 (general anxiety disorder 7) and PHQ-9 (patient health questionnaire-9) instruments. Of the 83 participants in the first screening, 26 (31.3%) had ≥ 1 positive test results. This group more frequently had ≥ 1 family member with T1D than those with negative results (30.8 versus 5.3% respectively, p = 0.003). In the second screening stage, 13 participants (50%) tested negative for all 4 AAs, 9 (10.8%) had one positive AA (AA +), one participant had two AA + , and three children had three AA + . At the time of the second screening, all participants had normal glycaemic measurements, negative results for celiac disease and autoimmune thyroiditis screening. During observation period, two participants developed stage 3 T1D. Following the OGTT, another participant was diagnosed with stage 2 T1D, but two other participants with ≥ 2 AA + remained normoglycemic. The overall prevalence of depression and anxiety was similarly high among parents of children with both positive and negative T1D screening results; however, parents in the positive screening group more frequently exhibited severe anxiety.

Positive T1D screening with ≥ 2 AAs was observed in 5 (6.02%) participants. Three participants progressed to stage 2 or stage 3 T1D during follow-up, corresponding to a positive predictive value of 60%, within a relatively short observation period of 10-24 months. These findings support the implementation of T1D screening in Latvia, particularly in high-risk populations.

• Islet AA testing for several years has been used to screen for T1D in multiple international studies and national screening programs. • Timely detection of islet AA can prevent from DKA development and ensure presymptomatic insulin treatment with fewer complications.

• These data are of particular significance, because no prior screening initiatives for T1D have been reported in Latvia. • There is an urgent need to improve recognition of T1D in Latvia to decrease rates of DKA and other complications, and screening could be an effective tool for that.