Aim: To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction. Methods: Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age-and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. Result: Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71 +/- 0.93 ng/ml versus 2.69 +/- 2.02 ng/ml, p = 0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452 +/- 0.254 ng/ml versus 0.409 +/- 0.275 ng/ml, p > 0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR) = 1.71, 95% confidence interval (1.30-2.25); p < 0.0001]. Conclusion: The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group. (C) 2011 Elsevier Ireland Ltd. All rights reserved.