Abstract 021: Retinol Binding Protein-4 and Fetuin-A Predict Incident Metabolic Syndrome and Metabolic Tracking Prospectively in Younger Adults: A Multimarker Adipokine Panel Approach from the Framingham Study

Abstract

Introduction: Recent investigations have highlighted the central role of mediators produced by adipose tissue in the pathogenesis of metabolic dysregulation. We evaluated a multimarker panel of 6 adipokines (adiponectin, leptin, leptin receptor, fetuin-A, adipocyte-fatty acid binding proteins, retinol binding protein-4 [RBP4]) and related them prospectively to the incidence of metabolic syndrome (MetS) and change in metabolic traits on follow-up in a community-based sample of younger adults. We hypothesized that these adipokines would be associated with incidence of MetS and with longitudinal tracking of its components. Methods and Results: We evaluated the adipokine panel measured in 2208 Framingham third generation cohort participants (55% women; mean age 40 years). On follow-up (mean 6 years), 253 individuals developed new-onset MetS. After adjustment for standard clinical risk factors, the multimarker adipokine panel was associated with incident MetS (P = 0.002). Using a backward elimination process, both RBP4 and fetuin-A were significantly associated with development of MetS (multivariable-adjusted OR per 1-SD increment log marker, 1.23 [P= 0.01] and 1.17 [P= 0.03], respectively). Using the group with both the RBP4 and fetuin-A under the median serving as the referent, individuals with levels of both RBP4 and fetuin-A above the median experienced an increased risk for developing MetS (multivariable adjusted OR = 1.7 [95% CI, 1.10 - 2.65], P = 0.01). In multivariable adjusted logistic regression models, both RBP4 and fetuin-A were significantly associated with an increase in systolic BP (P =0.004 and P = 0.045, respectively) and increased fasting glucose. In addition, RBP4 was significantly associated with longitudinal increase in diastolic BP (P = 0.007). Conclusions: Our findings, based on prospective follow-up of a large community-based sample of younger adults, suggest higher levels of RBP4 and fetuin-A are associated with incident MetS and may constitute potential future therapeutic targets.