PB0507 - Insulin resistance links to procoagulant clot properties in young adult with type 1 diabetes: a cross-sectional observation study

Background: Individuals with Type 1 diabetes (T1D) and concomitant insulin resistance (IR) have a higher risk of vascular complications. Previous work has shown that fibrin clot properties can determine vascular risk.

Aims: We investigated the fibrin network in individuals with T1D and different degrees of IR, measured as estimated glucose disposal rate (eGDR).

Methods: A validated turbidimetric assay was employed to study plasma-derived fibrin clot properties in 47 individuals with T1D. HbA1c, waist circumference, and presence of hypertension were used to calculate eGDR using an established formula. Patients were categorised into eGDR tertiles and plasma clot maximum turbidity and time to 50% lysis were assessed in each group. In addition to plasma clots, we investigated the effects of IR on clots made from purified fibrinogen to understand whether IR induces qualitative changes in fibrinogen that results in altered clot characteristics.

Results: Plasma clot maximum absorbance, a measure of clot density, was highest in the low eGDR tertile compared to the middle (T2) and high tertiles (T3) (0.22+/-0.07, 0.19+/-0.04 and 0.17+/-0.04 AU, respectively; p = 0.004, T1 vs T3). Moreover, clot lysis time, an indicator of fibrinolysis potential, was longest in low eGDR tertile compared with middle and high (588+/-163, 523+/-104 and 47087 sec, respectively; p=0.02, T1 vs T3). Clots made from fibrinogen (1mg/ml) purified from pooled plasma of individuals with eGDR < 7 were denser than those with eGDR 7-7.9 or eGDR>8 (23.3+/-1.9, 22.4+/-1.1 and 22.1+/-1.0 fibers/100μm; p=0.02, eGDR < 7 vs eGDR>8), analysed using confocal microscopy.

Conclusion(s): IR is associated with procoagulant clot properties in individuals with T1D due, at least in part, to qualitative changes in fibrinogen. This may represent one mechanism for increased vascular risk in T1D individuals with concomitant IR.