Fatty Acid-Binding Protein 4 and Risk of Type 2 Diabetes, Myocardial Infarction, and Stroke: A Prospective Cohort Study

Context: Adipocyte fatty acid-binding protein (FABP4) is expressed in adipose tissue and may impair glucose homeostasis and promote atherosclerotic processes. Objective: We examined the association between serum FABP4 and risk of type 2 diabetes (T2D), myocardial infarction (MI), and stroke. Design: Case-cohort study embedded within a sample of 27,548 participants of the EPIC-Potsdam cohort. Participants and Setting: A randomly selected subcohort (n=2194) of participants who were free of cardiovascular disease and T2D at study baseline and 728 incident T2D cases, 206 incident stroke cases, and 185 incident MI cases with an average 8.2 (+/- 1.7) years of follow-up. Main Outcome Measures: Incident T2D, MI, and stroke. Results: In amultivariable-adjustedmodel, the hazard ratios (HRs) in the highest vs lowest quartile of FABP4 were 1.81 (95% CI, 1.21 to 2.70; P-trend = 0.01) for T2D, 0.93 (95% CI, 0.55 to 1.55; P-trend = 0.68) forMI, and 1.41 (95% CI, 0.80 to 2.49; P-trend = 0.24) for stroke, respectively. In analyses stratified by sex, no statistically significant differences could be seen for associations between FABP4 and T2D and MI (P-interaction by sex 5 0.27 and 0.84, respectively), whereas a higher risk of stroke was observed in men (HR: 2.70, 95% CI 1.20 to 6.00; P = 0.04), but not in women (HR: 0.70, 95% CI 0.31 to 1.60; P = 0.53; P-interaction = 0.02). Conclusions: These data support the hypothesis that elevated FABP4 levels may contribute to T2D risk. In contrast, our data did not support the hypothesis that circulating FABP4 may be relevant for MI, whereas the observed association with stroke in men may need further evaluation.