Plasma levels of FABP4, but not FABP3, are associated with increased risk of diabetes.

Little is known about the association between plasma concentrations of fatty acid binding protein 3 and 4 and the risk of diabetes in population-based cohorts. In a prospective nested case-control design, we studied 149 cases of diabetes and 149 matched controls from the Physicians' Health Study. Plasma fatty acid binding proteins were measured on frozen specimens collected between 1995 and 2001 by ELISA. Cases of diabetes were self-reported and validated in a subsample via review of medical records. We used conditional logistic regression to estimate multivariable relative risks. The mean age at baseline was 64.9 years and median plasma fatty acid binding protein 3 and 4 were 2.12 ng/ml (IQR 1.62-2.66) and 15.32 ng/ml (IQR 12.14-18.73), respectively. In separate models, each fatty acid binding protein was positively associated with the risk of diabetes in a conditional logistic regression adjusting for matching variables, smoking, and hypertension. However, upon adjustment for each other, only fatty acid binding protein 4 (but not 3) was positively associated with the risk of diabetes [relative risk (95 % CI) 1.0 (reference), 2.73 (1.08-6.89), 2.66 (1.11-6.42), and 6.89 (2.83-16.80) across consecutive quartiles of fatty acid binding protein 4, P for trend <0.0001]. The FABP4-diabetes association was modified by body mass index (P interaction 0.03). Our data showed a positive association between plasma fatty acid binding protein 4 but not 3 and the risk of diabetes in US male physicians. The interaction with body mass index warrants further investigations.