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

Abstract

IntroductionType 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 methodsWe studied 744 individuals from the Hoorn Study (275 NGM, 176 IGM and 293 DM2, mean age 68.6±7.1years). 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. ResultsAfter adjustment for age, sex, prior CVD and smoking status, individuals with IGM or DM2 had a longer lag time [ß=0.14min (95% CI: 0.02; 0.26)], higher peak height [ß=7.29 nM (−1.33; 15.91)] and ETP [ß=35.65nM*min (0.97; 70.34)] than those with NGM. These differences were attenuated to ß=0.06min (−0.07; 0.19), 3.82nM (−5.46; 13.10) and 16.34nM*min (−20.92; 53.59), respectively, when further adjusted for waist circumference and hsCRP. ConclusionIndividuals 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.