What are the recommendations for screening for type 1 diabetes, particularly in pediatric and young adult populations with a family history of type 1 diabetes or symptoms such as polyuria, polydipsia, and unexplained weight loss?

Screening for Type 1 Diabetes

Screen children and adults with a first-degree relative with type 1 diabetes or those from the general population with high-risk genetic factors using islet autoantibody testing, as the presence of two or more autoantibodies confers a 70% risk of developing clinical diabetes within 10 years and 84% within 15 years. 1

Who Should Be Screened

High-Risk Populations Requiring Screening

• First-degree relatives of individuals with type 1 diabetes should be offered islet autoantibody screening through research studies (e.g., TrialNet) and national programs for early diagnosis 1
• Children from the general population can be effectively screened, as 90% of individuals who develop type 1 diabetes have no family history 1, 2
• Individuals with other autoimmune diseases including celiac disease, autoimmune thyroid disease, Addison's disease, juvenile idiopathic arthritis, vitiligo, and myasthenia gravis have increased risk and warrant consideration for screening 3
• Patients on immune checkpoint inhibitors (particularly those with HLA-DR4) should be monitored, as 76% of checkpoint inhibitor-related type 1 diabetes cases occur in this genetic subgroup 1

Symptomatic Individuals Requiring Immediate Testing

• Any child or adult presenting with polyuria, polydipsia, and unexplained weight loss requires immediate blood glucose measurement, not screening—this is diagnostic testing 1
• Additional acute symptoms include polyphagia, fatigue, and blurred vision occurring over days to weeks 1
• 25-50% of individuals are diagnosed with life-threatening diabetic ketoacidosis at presentation, making early identification critical 1

Screening Methodology

Autoantibody Panel

• Test for multiple islet autoantibodies simultaneously: GAD antibodies (GADA), IA-2 antibodies (IA-2A), zinc transporter 8 antibodies (ZnT8A), and insulin autoantibodies (IAA) 4
• Two or more positive autoantibodies define high risk and Stage 1 type 1 diabetes 1
• Single autoantibody positivity confers only 15% risk of progression within 10 years, versus 70% with two or more antibodies 4

Genetic Screening Considerations

• High-risk HLA genotypes (particularly HLA-DR4) can identify candidates for autoantibody screening in general population programs 1
• Genetic screening alone is insufficient—autoantibody testing remains the definitive risk marker 1

Screening Timing and Frequency

Optimal Age for Screening

• Screen children from the general population starting at age 2-3 years, as this captures the peak age of autoantibody seroconversion 1, 5
• For first-degree relatives, screening can begin earlier given higher baseline risk 2
• Repeat screening every 1-2 years in high-risk individuals with single autoantibody positivity or strong family history 5

Confirmation Testing

• Confirm positive autoantibody results with repeat testing using a different assay or laboratory to prevent misdiagnosis 5
• False positives occur, particularly with single autoantibody positivity, making confirmation essential before counseling about high risk 5

Risk Stratification After Positive Screen

Stage 1 Type 1 Diabetes (Two or More Autoantibodies, Normoglycemia)

• 70% progress to clinical diabetes within 10 years, 84% within 15 years 1
• Monitor with metabolic assessments every 3-6 months including fasting glucose, oral glucose tolerance testing, and HbA1c 4
• Consider teplizumab therapy to delay progression to clinical disease in eligible individuals 4

Stage 2 Type 1 Diabetes (Two or More Autoantibodies, Dysglycemia)

• Defined by impaired fasting glucose (100-125 mg/dL) or impaired glucose tolerance (2-hour glucose 140-199 mg/dL) or HbA1c 5.7-6.4% 1
• Higher and more imminent risk of progression to Stage 3 requiring insulin 1
• Intensify monitoring to every 3 months with glucose testing 4

Management of Screen-Positive Individuals

Immediate Actions

• Educate patients and families about symptoms of hyperglycemia (polyuria, polydipsia, weight loss) requiring urgent medical attention 1
• Provide written action plans for recognizing diabetic ketoacidosis symptoms 1
• Close follow-up prevents DKA at diagnosis—studies show screening programs reduce DKA rates from 40% to <5% at clinical onset 2

Screening for Associated Conditions

• Test for thyroid autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin) soon after positive islet autoantibody screen 1, 4
• Screen for celiac disease with IgA tissue transglutaminase antibodies (with total IgA level documentation) at time of autoantibody positivity 1, 6
• Repeat celiac screening within 2 years, then at 5 years 6

Critical Pitfalls to Avoid

• Do not delay diagnostic testing in symptomatic individuals by ordering autoantibody screening—measure blood glucose immediately if classic symptoms present 1
• Do not screen the general asymptomatic population without risk factors—the yield is too low and false positives create unnecessary anxiety 1, 7
• Do not diagnose type 1 diabetes based on autoantibodies alone—hyperglycemia meeting diagnostic criteria must be present for Stage 3 diagnosis 1
• Avoid testing thyroid function at time of diabetes diagnosis if patient is in DKA or has recent hyperglycemia, as results may be misleading (euthyroid sick syndrome) 1

Current Limitations

While population-wide screening is feasible and identifies the 90% of cases without family history, routine clinical implementation outside research programs is not yet recommended due to infrastructure requirements for counseling, monitoring, and intervention 1, 2. However, targeted screening in high-risk groups (first-degree relatives, other autoimmune diseases) should be offered through established programs like TrialNet 1, 2.