Background Diabetes confers an increased risk for cardiovascular effects of airborne particles. Soluble CD40L decreased with UFP exposure. Plasma von Willebrand factor increased immediately after exposure. There were no effects of particles on plasma tissue factor coagulation factors VII or IX or D-dimer. Conclusions Inhalation of elemental carbon UFP for 2-hr transiently activated platelets and possibly the vascular endothelium in people with type 2 diabetes. perfusion chamber and also increased formation of platelet-neutrophil and platelet-monocyte aggregates which are markers of platelet activation (Lucking et al. 2008). However these exposures contained both particulate and gaseous emissions at relatively high concentrations so the causative agent or agents is unknown. CREB-H We have shown previously that inhalation of UFP consisting of elemental carbon as surrogates for UFP of combustion origin subtly altered both pulmonary and systemic vascular function in healthy subjects (Frampton et al. 2006 2007 Shah et Ritonavir al. 2008). We hypothesized that inhalation of carbon UFP without the gases and reactive organic molecules that are present in diesel exhaust would activate vascular endothelium and blood platelets and promote coagulation in subjects with type 2 diabetes. Materials and Methods The Research Subjects Review Board of the University Ritonavir of Rochester approved the study. Informed written consent was obtained from all subjects. Subjects Volunteers were 19 never-smokers 30-60 years of age with type 2 diabetes as defined by the World Health Organization (Alberti and Zimmet 1998). Subjects were recruited in Rochester New York using media advertisements; 38 persons were screened and 19 of those screened met the study criteria and completed the study. We attempted to balance subject recruitment by sex and age (30-45 vs. 46-60 years old). Subjects were required to be on a stable medication regimen for at least 3 months prior Ritonavir to entry and were continued on the same regimen during the study. Exclusion criteria included clinical cardiovascular disease major organ dysfunction uncontrolled hypertension frequent hypoglycemia statin-type lipid-lowering medications (because of the anti-inflammatory effects of these medications) platelet-active drugs including aspirin and occupational exposure to particles (e.g. welding foundry work). Subjects were asked to avoid nonsteroidal antiinflammatory drugs and phosphodiesterase enzyme inhibitors during the study and were questioned Ritonavir regarding compliance at each visit. Protocol This study was a double-blind randomized crossover design in which each subject inhaled both filtered air (0-10 particles/cm3) and elemental carbon UFP (50 μg/m3 count median diameter of 32 nm) by mouthpiece for 2 hr at rest with at least 3 weeks separating the exposures. Subjects were admitted to the University of Rochester General Clinical Research Center the evening prior to exposure and remained overnight. Baseline blood measurements were performed at approximately 0900 hours the following morning. The exposures began at approximately 0930 hours. The first measurements occurred at 1200 hours (0.5 hr after completion of the exposure) and again at 1530 hours (3.5 hr after exposure). The subjects were then allowed to leave the center and returned the following 2 days for blood draws at 0900 hours (21 and 45 hr after the end of the exposure). Details of particle generation and characterization have been published previously (Chalupa Ritonavir et al. 2002). The particles were generated in argon using an electric spark discharge between graphite electrodes in a commercial generator (Palas Aerosol Generator model GFG-1000; Palas Co. Karlsruhe Germany) modified to prevent off-gassing of organic materials from within the generator (McDonald et al. 2001). This produced particles consisting of > 95% elemental carbon without metals. Particle number (condensation particle counters Model 3220a; TSI Inc. St. Paul MN) mass (tapered element oscillating microbalance; Rupprecht and Patachnick Albany NY) and size distributions (Scanning Mobility Particle Sizer.