Impaired glucose metabolism and type 2 diabetes are associated with hypercoagulability: potential role of central adiposity and low-grade inflammation - The Hoorn Study

Introduction: Type 2 diabetes (DM2) is associated with greater risk for cardiovascular disease (CVD), which may, at least partially, be explained by prothrombotic alterations. We therefore investigated; first, the extent to which individuals with impaired glucose metabolism (IGM) and/or DM2 had greater levels of thrombin generation than those with normal glucose metabolism (NGM); and second, whether any differences were independent of other cardiovascular risk factors, such as smoking, hypertension, dyslipidaemia, (micro) albuminuria, glycemic control and (central) adiposity, and/or were potentially 'mediated' by low-grade inflammation (high-sensitivity C-reactive protein (hsCRP)). Materials and methods: We studied 744 individuals from the Hoorn Study (275 NGM, 176 IGM and 293 DM2, mean age 68.6 +/- 7.1 years). Thrombin generation in platelet-poor plasma was measured using the Calibrated Automated Thrombogram and three parameters were derived: lag time, peak height and endogenous thrombin potential (ETP). Data were analyzed with multiple linear regression analyses. Results: After adjustment for age, sex, prior CVD and smoking status, individuals with IGM or DM2 had a longer lag time [beta=0.14 min (95% CI: 0.02; 0.26)], higher peak height [beta=7.29 nM (-1.33; 15.91)] and ETP [beta=35.65nM* min (0.97; 70.34)] than those with NGM. These differences were attenuated to beta=0.06 min (-0.07; 0.19), 3.82 nM (-5.46; 13.10) and 16.34 nM*min (-20.92; 53.59), respectively, when further adjusted for waist circumference and hsCRP. Conclusion: Individuals with IGM or DM2 had up to 4% higher thrombin generation compared with NGM, which may be explained, to a great extent, by the greater levels of central adiposity and related low-grade inflammation characterizing these individuals.