Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study

Background Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross‐sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS. Methods and Results Participants in the community‐based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002–2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin‐A, fatty acid–binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow‐up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m 2 ) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal‐weight with MetS (metabolically obese, normal‐weight) with normal‐weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin‐A and fatty acid–binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin ( P <0.001 for all). The adipokine panel was associated with incident MetS (263 new‐onset cases; P =0.002). Higher circulating concentrations of retinol‐binding protein 4 and fetuin‐A were associated with incidence of MetS (odds ratio per 1‐ SD increment log marker, 1.21; 95% CI , 1.03–1.41 [ P =0.02] and 1.17; 95% CI, 1.01–1.34 [ P =0.03], respectively). Conclusions In our community‐based sample of young to middle‐aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol‐binding protein 4 and fetuin‐A marked future cardiometabolic risk.