How to act in the face of seroconversion?

Abstract

Autoimmunity in type 1 diabetes mellitus (T1DM) is identified by the presence of circulating antibodies against β-cell antigens (seroconversion), which are typically detected well before the clinical onset of diabetes. Islet autoantibodies include GADA, IAA, IA-2A, and ZnT8A.

T1DM can be described in stages: the presence of two or more autoantibodies with normoglycemia (Stage 1) or dysglycemia (Stage 2), or glucose levels meeting ADA criteria for diabetes (Stage 3).

Guidelines are currently available for developing monitoring plans during preclinical stages. Interdisciplinary support is crucial and should be based on education, metabolic monitoring, and psycho-emotional support.

Monitoring frequency depends on the individual's stage and age. A single positive autoantibody indicates an increased risk (15%) of T1DM. Metabolic monitoring is performed every 6 months for children under 3 years of age (for 3 years), followed by annual monitoring for another 3 years.

For children over 3 years old, monitoring is annual for 3 years. For adults, it is performed every 3 years, or potentially annually for those with a first-degree relative with T1DM, increased genetic risk, a history of dysglycemia, or stress-induced hyperglycemia. Stage 1 monitoring: every 3 months for those under 3 years old, every 6 months for ages 3 to 9, and every 12 months for children over 9 and adults.

Stage 2 monitoring: every 3 months for children and every 6 months for adults. Various tools exist to assess the risk of progression to clinical Stage 3. The oral glucose tolerance test (OGTT) remains the gold standard for staging T1DM, although it can be complex due to the need for multiple blood draws, particularly in young children.

HbA1c: A complementary measure that, alongside CGM, provides a fairly robust prediction of progression; it is more feasible and serves as a less invasive alternative to the OGTT. A 10% increase—even within the normal range—during follow-up indicates a risk of progression. It can be affected by other conditions that alter hemoglobin.

CGM: Useful and easily accessible. Observational studies have shown that spending 10% of the time above 140 mg/dL predicts an 85% risk of progression within one year. Capillary monitoring: Accessible and useful for home use during intercurrent illnesses. C-peptide: A universal marker of beta-cell function. Early detection alone does not alter the natural history of T1DM; what changes the course of the disease is the support provided following diagnosis during preclinical stages.