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Soluble adhesion molecules in pre-clinical Type 1 diabetes: a prospective study
A M Toivonen1, P Kulmala, K Savola
1Medical School, University of Tampere and Department of Paediatrics, Tampere University Hospital, Tampere, Finland.
Diabetologia
|April 10, 2003
Summary
Soluble intercellular adhesion molecule-1 (ICAM-1) levels were higher in siblings who developed Type 1 diabetes. However, ICAM-1 and L-selectin are not reliable predictors for identifying prediabetic individuals who will progress to clinical diabetes.
Area of Science:
- Immunology
- Endocrinology
- Diabetology
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic beta cells.
- Identifying individuals at high risk for T1D progression is crucial for early intervention.
- Adhesion molecules play a role in immune cell trafficking and inflammation, potentially involved in T1D pathogenesis.
Purpose of the Study:
- To evaluate serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and L-selectin in siblings with pre-clinical T1D.
- To determine if these adhesion molecules correlate with autoantibody status.
- To assess the potential of ICAM-1 and L-selectin to differentiate between siblings who progress to clinical T1D and those who remain non-diabetic.
Main Methods:
- A prospective case-control study involving autoantibody-positive siblings of children with T1D.
- Serum levels of ICAM-1 and L-selectin were measured using enzyme-linked immunosorbent assays over a 10-year observation period.
- Participants were categorized into progressors (developed T1D) and non-progressors (remained T1D-free).
Main Results:
- Significant variability in soluble adhesion molecule concentrations was observed in both progressors and non-progressors.
- Integrated ICAM-1 concentrations were higher in progressors, particularly 18-24 months before diagnosis (p=0.015).
- Integrated L-selectin concentrations and adhesion molecule levels did not differ significantly between progressors and non-progressors in relation to autoantibody status.
Conclusions:
- The findings suggest that the autoimmune process in T1D may initiate years before clinical manifestation, with peak activity around 1.5 years prior to diagnosis.
- Peripheral concentrations of ICAM-1 and L-selectin are not sufficiently distinct to identify prediabetic individuals who will inevitably progress to T1D.
- Substantial overlap in adhesion molecule levels between progressors and non-progressors limits their utility as predictive biomarkers for T1D development.