Context: High retinol-binding protein 4 (RBP4) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations is scarce about relationship between RBP4 and metabolic diseases.

Objective: We evaluated plasma RBP4 distribution and its association with metabolic syndrome (MetS) among middle-aged and older Chinese.

Research Design and Methods: We evaluated plasma RBP4 in a cross-sectional sample of 3289 Chinese aged from 50 to 70 years in Beijing and Shanghai by utilizing an in-house developed and validated sandwich enzyme-linked immunosorbent assay. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results: RBP4 levels were higher in male and Beijing residents, compared to female and Shanghai participants (both P < 0.001). RBP4 levels were associated positively with body mass index (BMI), waist circumference, triglyceride, total and low-density lipoprotein cholesterol, blood pressure, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), while negatively with high-density lipoprotein cholesterol and adiponectin (all P < 0.001). In the highest RBP4 quartile, the MetS risk was significantly higher (odds ratio [OR]: 2.58; 95% confidence interval [CI]: 2.08–3.20) than in the lowest quartile after adjustment for potential confounders. This association remained strong (OR: 2.25; 95% CI: 1.72–2.94) after further controlling for C-reactive protein, adiponectin, HOMA-IR and BMI.

Conclusions: This first large-scale population study shows elevated RBP4 levels are strongly and independently associated with MetS. Prospective studies are needed to establish the role of RBP4 in the development of MetS and related diseases.