Serum lipopolysaccharide-binding protein levels and the incidence of metabolic syndrome in a general Japanese population: the Hisayama Study

Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population.Methods: 1,869 community-dwelling Japanese individuals aged >= 40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1- 4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 mu g/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model.Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59- 5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend=0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend=0.07).Conclusions: In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.