Consensus Guidance for Monitoring Children with Islet Autoantibody-Positive Pre-Stage 3 Autoimmune Type 1 Diabetes (T1D)

Screening and monitoring are critical to managing autoimmune T1D and reducing the likelihood of diabetic ketoacidosis (DKA) hospitalization or emergency care at the time of Stage 3 autoimmune T1D diagnosis.¹

Testing for islet autoantibodies against four major pancreatic autoantigens is currently available:

A combination of these four primary types of autoantibodies is recommended to detect autoimmunity.^1-3

The presence of islet autoantibodies alongside metabolic status defines the three stages of T1D.⁴

These screening criteria are recommended by the most recent ADA Standards of Care.¹

At-risk ≤1 autoantibody
Normoglycemia

How to confirm single IAb⁺ status¹

CONFIRM RESULTS
	After first detection of single IAb, follow the ‘rule of twos’, using two independent methods to confirm negative results for other IAbs.1
MONITORING FREQUENCY (children <3 years old)
	Monitor IAb+ status every 6 months for 3 years, then annually thereafter for 3 more years.1
	Metabolic monitoring includes random venous or capillary blood glucose and HbA1c values at the same frequency.1
	If no progression, stop autoantibody and metabolic monitoring and counsel for risk of clinical disease.1
MONITORING FREQUENCY (children ≥3 years old)
	Monitor IAb+ status annually for 3 years.1
	Metabolic monitoring includes annual random venous or capillary blood glucose and HbA1c testing for 3 years.1
	If no progression, stop autoantibody and metabolic monitoring and counsel for risk of clinical disease.1

Critical monitoring during early years (first two years after seroconversion):1 Islet autoantibody status and metabolic monitoring are most critical during this time. Ongoing metabolic monitoring is not essential beyond this period.

Stage 1 (early stage) ≥2 autoantibodies
Normoglycemia

How to confirm multiple IAb+ status¹

CONFIRM RESULTS
	After first detection of ≥2 IAbs, follow the ‘rule of twos’, using two independent methods to confirm positive status for other islet autoantibodies.1

	TWO-TEST CONFIRMATION NOT POSSIBLE? A single blood test positive for multiple islet autoantibody status identifies a person with sufficient risk for metabolic monitoring.1
	REVERTED STATUS? For adults with previously confirmed multiple IAb+ status who revert to single IAb+ or IAb− status, metabolic monitoring should follow the guidelines below for Stage 1.1

GENERAL GUIDELINES FOR METABOLIC MONITORING¹

	Conduct monitoring based on staging criteria and modalities described in Tables 1 and 5 of the consensus guidelines.1
	Ensure monitoring is done when the child is healthy and not experiencing intercurrent illness.1
	Provide SMBG meters and strips to all children with multiple islet autoantibody positivity or their parents.1
	During intercurrent illness (e.g., a cold), use SMBG to detect hyperglycemia.1
	For recent confirmation of multiple IAb+ status, perform SMBG tests on two different days over a 2-week period, then once every 1–3 months.1

Stage 2 (early stage) ≥2 autoantibodies
Glucose intolerance or dysglycemia

How to confirm multiple IAb+ status¹

CONFIRM RESULTS1
	After first detection of ≥2 IAbs, follow the ‘rule of twos’, using two independent methods to confirm positive status for other islet autoantibodies.1

	TWO-TEST CONFIRMATION NOT POSSIBLE? A single blood test positive for multiple islet autoantibody status identifies a person with sufficient risk for metabolic monitoring.1
	REVERTED STATUS? For adults with previously confirmed multiple IAb+ status who revert to single IAb+ or IAb− status, metabolic monitoring should follow the guidelines below for Stage 2.1

GENERAL GUIDELINES FOR METABOLIC MONITORING¹

	Monitor measures of glucose regulation (glycemic status) every 3 months.
	A longitudinal change in HbA1c of ≥10% from the confirmed islet autoantibody date may indicate dysglycemia and disease progression.1
	Perform an OGTT to assess T1D stage for therapy eligibility.1
	Measure random venous or capillary blood glucose simultaneously with HbA1c.1
	Use 10–14-day CGM periodically at a similar frequency as HbA1c measurement.1
	Monitor objective weight trends using a growth chart and ensure a healthy meal plan to preclude disordered eating behaviors as a cause of weight change.1

OGTT is the established gold standard to classify Stage 1, Stage 2 or Stage 3 T1D however if OGTT is not possible:1 Obtain a 2-hour postprandial capillary blood glucose measurement after a carbohydrate-rich meal to assess for dysglycemia.1

CGM usage
	CGM should be blinded to the individual and interpreted by trained HCPs.1
	Criteria for CGM metrics to diagnose Stage 2 or Stage 3 T1D require further research.1

All persons at risk through to Stage 2

PSYCHOSOCIAL SUPPORT FOR SINGLE AND MULTIPLE IAb+ INDIVIDUALS

	Emotional, cognitive and behavioral functioning should be assessed in people at risk of or with early-stage autoimmune type 1 diabetes and their family members, when appropriate. Anxiety, risk perception and behavior changes should specifically be assessed.1
	Ask the individual at risk or with early-stage type 1 diabetes and/or their caregivers and family members about their reactions upon receiving the news that they have type 1 diabetes-related autoantibodies. This can be accomplished using guiding questions and standardized and validated questionnaires.1
	At each monitoring visit, there should be enquiries into current needs, particularly coping.1
	Psychological care should be integrated into routine medical visits and, whenever possible, delivered by providers with diabetes-specific training.1

Stage 3 ≥1 autoantibodies
Persistent hyperglycemia with or without symptoms

Screening and subsequent monitoring for presymptomatic T1D prior to clinical onset of Stage 3 have several benefits, including reducing the risk of DKA and hospitalization, and providing opportunities for education and preparation for chronic disease management.^5,6

The decision to start insulin depends on a range of factors and consideration to do so should be referred to a specialist center.¹

For the full guidelines together with the evidence rating (A–E), please consult reference 1.

ADA, American Diabetes Association; CGM, continuous glucose monitoring; DKA, diabetic ketoacidosis; GAD, glutamic acid decarboxylase; HbA1c, glycated hemoglobin; HCP, healthcare professional; IA-2, insulinoma-associated antigen-2; IAA, insulin autoantibody; IAb, islet autoantibody; OGTT, oral glucose tolerance test; SMBG, self-monitoring of blood glucose; T1D, type 1 diabetes; T2D, type 2 diabetes; ZnT8, zinc-transporter 8.