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Serum thrombospondin (TSP)-2 is a glycoprotein expressed in extracellular matrix increasing during tissue remodeling. Recent studies have shown that TSP-2 is useful as a prognostic factor of patients with heart failure and associated with cardiovascular death. However, the clinical importance of serum TSP-2 in healthy subjects is still unknown. We examined the relations between TSP-2 and coronary risk factors.A periodic epidemiological survey was performed in a community dwelling in Uku town, Nagasaki, Japan. A total of 445 residents received a health check-up examination including blood tests such as fasting serum levels of TSP-2. Insulin resistance was evaluated using HOMA-IR. All statistical analyses were performed using SAS system.The mean age was 67 ± 9.4 years old. There are no significant differences between the ages and sexes and serum TSP-2 level (mean:20.9 ± 8.5 ng/mL). We performed uni and multivariate analyses. Serum TSP-2 levels were significantly correlated to plasma glucose (p < 0.001), insulin (p < 0.001), HOMA-IR (p < 0.001), eGFR (p < 0.01; inversely), high sensitive CRP (p < 0.01) and NT-proBNP (p < 0.001). Moreover, in multiple stepwise linear regression analysis, TSP-2 levels were independently and significantly associated with HOMA-IR (p < 0.001), high sensitive CRP (p < 0.05), and NT-proBNP (p < 0.001).To the best of our knowledge, this is the first report to examine the significant relationship between TSP-2 and insulin resistance even in healthy subjects.