How should individuals with positive T1D autoantibodies be monitored over time?

Key Takeaway

Metabolic monitoring in individuals who screened positive for ≥2 T1D autoantibodies to track progression of T1D¹

Primary purpose of monitoring is to potentially lower the risk of DKA at Stage 3 T1D diagnosis¹

Latest consensus guidance* recommends metabolic monitoring by choosing from multiple available tools, such as OGTT, random blood glucose checks, CGM, HbA1c testing, and SMBG.¹

Monitor early-stage T1D in primary care if the required skills and resources are available; refer to specialists upon onset of glucose abnormalities.¹

*Consensus report endorsed by EASD, ADA, AACE, ACD, ADCES, ADS, ISPAD, ATTD, DiaUnion, the Endocrine Society and JDRF International.

What are the next steps for individuals who test positive for T1D autoantibodies?

A positive screening for presence of ≥2 T1D antibodies indicate that the individual is in presymptomatic stage of T1D.² As per the latest consensus guidance, such individuals need metabolic monitoring for the presence of glucose abnormalities, an indicator of disease progression.^1,3,4

Presence of dysglycaemia, (fasting plasma glucose ≥100 mg/dL [≥5.6 mmol/L], 2-hour plasma glucose with 75 gm OGTT ≥140 mg/dL [≥7.8 mmol/L], 30/60/90 min glucose ≥200 mg/dL [≥11.1 mmol/L], and/or HbA1c ≥5.7% [≥39 mmol/mol]), in individuals who test positive for ≥2 T1D antibodies indicate Stage 2 T1D.³ Individuals in this stage have a 100% risk of progressing to symptomatic Stage 3 T1D within the next 15 years.² At this stage (Stage 2) you can provide such individuals and their caregivers the relevant disease-related education and psychosocial support needed to prepare for a possible Stage 3 T1D diagnosis.^4,5

What is the purpose of monitoring T1D autoantibodies and glycaemia?

The primary purpose of monitoring individuals with positive screening results for T1D antibodies is to potentially lower the risk of diabetic ketoacidosis (DKA) at Stage 3 T1D diagnosis.¹ DKA is a life-threatening condition which is associated with need for hospital admission and potential long-term complications.1 A lower risk of DKA is associated with lower incidence of severe hypoglycaemic events within 10 years post diagnosis.¹  Regular medical monitoring, including monitoring glucose abnormalities, will help identify disease progression early on.^1,4

Timely monitoring that helps in the early detection of Stage 3 T1D can enable you to promptly initiate early insulin therapy which will help to optimise HbA1c and potentially avoid long-term consequences of prolonged hyperglycaemia.¹ Monitoring further avoids misdiagnosis of type 2 diabetes and delay in treatment, and also it may increase patient referrals to clinical trials where appropriate.¹

Should you follow specific algorithms and tools to monitor individuals who test positive for T1D autoantibodies?

Monitoring of individuals who screened positive for islet autoantibodies can be largely divided into the two categories:

• Repeat antibody testing: Once an individual tests positive, the second confirmatory test should be done within 3 months.¹ A persistent presence of >1 autoantibody indicates presymptomatic Stage 1 T1D.¹ Repeat periodic assessments confirming presence of ≥2 autoantibodies along with onset of dysglycaemia indicates progression of disease to Stage 2 T1D.¹ 
• Metabolic monitoring: Choose from multiple available tools, such as regular oral glucose tolerance test (OGTT), random venous or capillary blood glucose, continuous glucose monitoring (CGM), HbA1c testing or self-monitoring of blood glucose (SMBG).¹ Testing C-peptide can help you assess measure of beta-cell function and distinguish stages of T1D.¹

A detailed description of the methods used for metabolic monitoring is provided in the table below.

At any point of monitoring if you observe onset of hyperglycaemia along with other clinical symptoms such as polyuria, polydipsia, weight loss, fatigue, hunger, blurry vision, and diabetic ketoacidosis (DKA), it indicates disease progression to symptomatic Stage 3 T1D.¹
 

The consensus guidance published in June 2024 provides a detailed algorithm for monitoring of individuals who have been screened positive for islet autoantibodies.¹ Below figure illustrates an algorithm for monitoring of people screened positive for ≥2 islet autoantibodies.¹

Decision path for monitoring of individuals screened positive for ≥1 islet autoantibodies¹

Adapted from Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetologia. Published online June 24, 2024.

*Monitoring frequency and methodology depends on age, length of time since first detection of islet autoantibody, number of islet autoantibodies detected and presence of symptoms of type 1 diabetes.

Ab, antibody; GP, general practitioner; PRN, pro re nata  (as needed); Sx, symptoms; T1D, type 1 diabetes

Are there any differences in metabolic monitoring approach in children versus adults?

Progression of T1D among islet autoantibody-positive adults is slower than children, which is why there are minor variations in monitoring approaches.¹ You can follow a more frequent metabolic monitoring for children compared to adults.¹ Also, children who have progressed to Stage 2 T1D need to be followed up in a specialty care setting.¹ Refer to the figure below for more details.

Where should the monitoring be conducted?

Monitoring should be conducted wherever there are the necessary skills and resources to perform the required tests. Early stage (Stage 1 T1D) monitoring can be done in primary-care setting. As soon as you observe indicators of progression of disease to Stage 2 T1D i.e. onset of glucose abnormalities, consider referring to specialty care provider.¹