ISPAD 2025 Symposium Summary

• Screening for T1D autoantibodies can detect early stage T1D months to years before onset of symptoms, enabling intervention in Stage 1 (≥2 IAbs + normoglycemia) and Stage 2 (≥2 IAbs + dysglycemia) disease.^1,2 
• Screening for all four primary autoantibodies (GADA, IA-2A, IAA, ZnT8A) are recommended to optimize early detection sensitivity and improve diagnostic accuracy for presymptomatic T1D.^3-5
• T1D screening programs demonstrate significant reduction in diabetic ketoacidosis (DKA) rates at diagnosis - Fr1da study showed lower DKA rates compared to unscreened populations, particularly critical for children below <10 years who have 30% DKA risk.^6,7
• Breakthrough T1D consensus recommends general population screening achieving 80% sensitivity with optimal cost-effectiveness at all three ages points (2–4 years, 6–8 years, and 10–15 years). Very young children (≤2 years) have an 87% 10-year progression risk to Stage 3 T1D compared to 44% in older children (>7.4 years), requiring more intense monitoring.⁸
• Only ~10% of individuals with T1D have a first-degree relative with the condition, making population-wide screening necessary to capture majority of cases rather than family-based screening alone.^9-14 
• Children with ≥2 IAbs have nearly 100% lifetime risk of developing clinical T1D (Stage 3) regardless of family history, emphasizing the importance of early identification and family education^15-17. ISPAD guidelines recommend frequent follow-up every 3 months for children <3 years with Stage 1, every 6 months for ages 3–9 years, and every 12 months for ≥9 years.¹⁸
• Early identification reduces parenting stress (11.8-point PIP score improvement), prevents employment disruption in mothers (32.7% work reduction avoided), and improves long-term outcomes through proactive management.^19,20

• Multiple international programs (Fr1da-Germany, ASK-US, TEDDY, ELSA-UK) demonstrate feasibility of population screening with >500,000 children screened globally, showing consistent clinical benefits and cost-effectiveness potential.

   

Talking Transformation with Young People and Their Families

• Healthcare professionals (HCPs) must acknowledge and validate the wide range of emotions (anxiety, shock, guilt, anger, grief) that children and families might experience upon confirmation of IAb positivity, with ~75% of parents in the ASK program showing anxiety symptoms after their child tested positive.^1-3
• Less than half (48.9%) of parents perceive their child as being at increased risk for T1D at the first monitoring visit after testing positive for IAbs, with factors such as lower parental education, single IAb positivity, lack of T1D familiarity, and ethnicity associated with lower risk perception.^3,4
• HCPs should find the right balance between healthy concern and excessive anxiety, use simple language avoiding medical jargon, employ consistent vocabulary when referring to T1D stages, and engage in active two-way conversations with families.^5-8 Age-appropriate communication is essential when communicating with children and adolescents.^1,9
• Accurate perception of risk is associated with staying engaged in monitoring and prevention of DKA. Signs and symptoms of hyperglycemia should be clearly communicated in writing, with awareness that symptom denial is frequent and symptoms are often attributed to unrelated factors. ^1,9-11
• Children and adolescents with T1D have more than 2-fold increased risk of mental health disorders compared to controls, with anxiety, mood/depressive disorders, eating disorders, and behavioral issues being most common.^11-15
• Psychosocial support should be integrated at each monitoring visit. HCPs should inquire about current needs and coping mechanisms with a low threshold for referral to T1D-trained mental health specialists. ^1,9
• When appropriate, responsibility for management should be gradually transferred from caregivers to young people with T1D, with conversations framed to encourage individual responsibility. HCPs should provide time to young people with T1D to share their level of understanding, perspectives, and preferences, knowing they can change their mind.^1,9
   

The Clinical Significance of Beta-cell Preservation in Early-stage T1D

• T1D results from autoimmune-mediated beta-cell dysfunction and destruction, progressing through distinct stages (Stage 1–4) from early autoimmunity with normoglycemia to long-standing disease with insulin dependence and often low/undetectable C-peptide levels.^1-3
• C-peptide serves as the primary biomarker for assessing beta-cell function, offering significant advantages over insulin measurement including constant clearance rate of 20–30-minute half-life, with no interference from exogenous insulin, and negligible hepatic extraction.^4-8
• Normal stimulated C-peptide levels are approximately 2.5–3.0 nmol/l, declining to 1.7–1.9 nmol/l in Stage 2, with 0.2 nmol/l commonly used as a cutoff for poor beta-cell reserve in Stage 3 T1D.^9-11
• A 20% decrease in C-peptide level from baseline is associated with 47% risk of progressing to Stage 3 T1D within 4 years, with 78% positive predictive value, demonstrating that decreased C-peptide levels are associated with increased risk of Stage 3 T1D.^12,13 C-peptide secretion rapidly decreased in individuals diagnosed during childhood and adolescence compared to adulthood, with greater variability in C-peptide decline rates observed among younger versus older individuals.¹⁴
• Higher residual beta-cell function is associated with achieving HbA1c <7.5% in 94% of children compared to only 18.4% in those with no detectable C-peptide.¹⁵
• Higher beta-cell function significantly reduces severe hypoglycemic events and lowers insulin requirements. Combined analysis of 21 randomized controlled trials (N=2711) showed that 24.8% higher C-peptide preservation at 6 months led to 0.55% reduction in HbA1c, with decreased rates of level 2/3 hypoglycemia (p<0.0001) and lower insulin doses.^16,17
• Higher beta-cell function is associated with 45% risk reduction for retinopathy and 39% risk reduction for nephropathy in longitudinal studies of individuals with T1D.¹⁸
• Despite improvements in management exogenous insulin, individuals with T1D face a constant burden. Therapeutic strategies to preserve beta-cell function target various aspects of the autoimmune process targeting autoimmune mechanisms, insulin sensitivity, and beta-cell regeneration essential for optimal T1D management.^19-22