Abstract 17744: In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes Mellitus
Introduction: While reduced responsiveness to low-dose aspirin has been associated with type 2 diabetes mellitus (T2DM), aspirin responsiveness remains unexplored in T1DM.
Hypothesis: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM) and platelet COX-1 inhibition, as assessed by serum TXB2 (sTXB2), in uncomplicated, normotensive, normolipidemic T1DM subjects on insulin therapy.
Methods: Upon informed consent, we enrolled 40 T1DM patients (26M, age 35±11yr, disease duration 16±11yr, BMI 24±2 kg/m2) and 10 healthy controls (6M, age 33±7yr). In 9 patients we assessed the stability of TXM excretion on 3 different visits. Thirty-one patients and all controls were given 100 mg daily aspirin for 21 days, and urinary TXM and sTXB2 were measured before and 24h after stopping aspirin. To assess the influence of glycemic variability on aspirin response, 26 patients underwent continuous glucose monitoring (CGM) for the first 24h after drug withdrawal.
Results: TXM excretion in T1DM was significantly higher than in controls (930 [659-1358] vs 568 [385-619] pg/mg creatinine; p<0.001) and quite stable across repeated sampling (p for linear trend = 0.755). By multivariate analysis, urinary TXM was associated with microalbuminuria (β=0.23; p=0.042) at baseline. The degree of inhibition at 24h after aspirin dosing was similar in T1DM and controls for both sTXB2 (98.2% vs 98.6%, p=0.607) and urinary TXM (68.8% vs 68.4%, p=0.962). CGM-derived mean and standard deviation glucose were not associated with sTXB2 or TXM inhibition at 24h.
Conclusions: We conclude that enhanced platelet activation in T1DM is independent of glycemic control and associated with kidney/endothelial damage. Moreover, in contrast to T2DM, the response to aspirin is unchanged, suggesting that the metabolic disturbance per se is not responsible for altered pharmacodynamics.
Author Disclosures: F. Zaccardi: None. F. Pagliaccia: None. A. Rizzi: None. G. Petrucci: None. A. Habib: None. L. Tanese: None. P. Rizzo: None. F. Martini: None. D. Pitocco: None. B. Rocca: None. C. Patrono: Other Research Support; Modest; Institutional grant for investigator-initiated research from Bayer. Speakers Bureau; Modest; Speaker fees from Bayer, Eli Lilly and Merck. Consultant/Advisory Board; Modest; Consultant fees from Bayer, Eli Lilly and Merck.
- © 2014 by American Heart Association, Inc.