182-LB: Circulating Adhesion Molecules and Relationships to Micro and Macrovascular Outcomes: The TODAY Study

Atherosclerosis begins in childhood, accelerating in those with obesity, hypertension and type 2 diabetes (T2DM). Binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in this process. The TODAY study, a clinical trial of adolescents with T2DM, included three treatment arms. The primary end-point was treatment failure defined as A1c persistently >=8% over 6 months period or metabolic decompensation. The aims of the present analysis are to evaluate: 1) changes in ICAM, VCAM, E-Selectin and MCP-1 over time 2) whether treatment group influences levels of these biomarkers and 3) the association of these markers with macrovascular and microvascular outcomes. Participants from the TODAY cohort (n=515) with at least two of the four annual assessments of adhesion molecules at baseline, 12, 24, 36 months were included. Over the study period, there were significant increases in ICAM (p=0.002) and MCP-1 (p<0.001) and significant decreases in VCAM (p<0.001) and E-Selectin (p=0.016) across the entire cohort. There were no significant treatment group interactions. Participants who reached the primary outcome had higher E-Selectin compared to participants with sustained control over the duration of the study (p<0.0001). ICAM increased 2.0% (p<0.001), VCAM increased 1.5% (p<0.001), E-selectin increased 7.0% (p<0.001), and MCP-1 increased 1.4% (p=0.001) for every 1% increase in HbA1c. E-selectin was 9.5% (p<0.001) and 5.2% (p=0.017) higher and ICAM was 5.9% (p=0.001) and 4.5% (p=0.046) higher in participants with microalbuminuria or hyperfiltration respectively. E-selectin increased with increasing left ventricular mass and TAPSE, a measure of right ventricular function, (p=0.043 and p=0.001, respectively). This analysis demonstrates cellular adhesion molecules increase with increasing HbA1c in youth with T2DM, and ICAM and E-selectin are associated with worsening micro and macrovascular outcomes.