Obesity and type 2 diabetes mellitus add up to induce platelet hyperreactivity and platelet activation

Platelet hyperreactivity and in vivo platelet activation, effectors of increased cardiovascular risk, have been associated with both type 2 diabetes (T2DM) and obesity, however, whether T2DM and obesity when combined further enhance platelet activation has not been explored.

We assessed several parameters of platelet reactivity and in vivo platelet activation, VWF activity and adipokine levels in 40 well characterized obese subjects without T2DM (metabolically healthy obese, MHO), non obese T2DM patients (metabolically unhealthy normal weight, MUNW), obese and T2DM patients (metabolically unhealthy obese, MUO) and age and sex-matched healthy controls (metabolically healthy normal weight, MHNW).

Both MUNW and MHO subjects showed enhanced platelet thrombus formation, increased response to collagen and ADP at light transmission aggregometry, raised urinary 11-dehydro-TxB₂, higher production of platelet reactive oxygen species and impaired platelet nitric oxide formation compared to MHNW, which were further significantly worsened in MUO. VWF activity and resistin levels were significantly higher in MUO patients compared to the other groups.

Our data show that the concomitant presence of T2DM and obesity exert a significant additive effect on platelet hyperreactivity and in vivo platelet activation compared with only one of these risk factors, and suggest that enhanced VWF and resistin levels in MUO subjects play a pathogenic role in the modulation of the platelet response to stimuli leading to a strong platelet hyperreactivity and in vivo platelet activation, in turn favoring enhanced cardiovascular risk.