Abstract 1319: Plasma Levels of Fatty Acid Binding Proteins 4 and 5 are Markers of Adiposity and the Metabolic Syndrome but are not Independent Predictors of Subclinical Atherosclerosis in Type 2 Diabetes
Objectives: Adipocyte-fatty acid binding protein (aP2) or FABP4 is expressed predominantly in adipose and macrophages. Its less abundant family member, FABP5 (Mal1), is more diffusely expressed but also found in adipocytes and macrophages. Gene deletion studies in rodents suggest that FABP4, to a greater extent than FABP5, modulates obesity and atherosclerosis. Preliminary clinical studies support a relationship of circulating FABP4 with obesity and the metabolic syndrome (MetSyn). However, there are no studies of circulating FABPs and atherosclerosis in humans.
Methods: We evaluated the association of FABP4 and 5 (ELISA, Biovender) with cardiovascular risk factors, NCEP-defined MetSyn and Coronary Artery Calcification (CAC) in 846 asymptomatic, type 2 DM subjects (62.5% Caucasian, 32.5% African-American; 60% male; aged 58.6±9.2) recruited to the Penn Diabetes Heart Study.
Findings: Levels [(median (IQ range)] of FABP4 [37.1 (23.0–55.2) vs 20.9 (14.0–31.0) ng/mL; p<0.001] and FABP5 [1.5 (1.2–1.9) vs 1.4 (1.1–1.8) ng/mL; p<0.01] were higher in women than men. FABP4 was significantly correlated with waist circumference (r=0.4, p<0.001), levels of leptin (r=0.5, p<0.001), insulin (r=0.21, p<0.001), hsCRP (r=0.23, p<0.001), triglycerides (r=0.25, p<0.001) and inversely with HDL cholesterol (women r=−0.23, p<0.001; men r=−0.11, p<0.05). Plasma FABP5 had similar, but weaker biomarker correlations. Both were strongly associated with MetSyn (FABP4 χ2=29.8, p<0.0001; FABP5 χ2=36.2, p<0.0001). Notably, FABP4 [22.7 (15.0–35.9) vs 34.4 (22.9–55.0), p<0.001], but not FABP5 (p<0.89), levels were lower in subjects on thiazolidinedione therapy. In tobit regression, FABP4, but not FABP5, levels above the median were associated with CAC scores after adjustment for age, gender and ethnicity [1.68 (1.05–2.66), Ratio (CI), p<0.03] but this was attenuated after further adjusting for BMI and established risk factors [1.52 (0.49–2.48), Ratio (CI), p<0.09].
Conclusion: Both FABP 4 and 5 are biomarkers of adiposity and MetSyn. In the first study of its kind, plasma FABP4, but not FABP5, was associated with CAC in type 2 DM, but neither were independent predictors of this subclinical atherosclerosis measure.