This study tested the hypotheses that correlations between direct measures of insulin sensitivity and proxy indices of insulin sensitivity derived from fasting values, (i) would not be affected by ethnicity, and (ii) would be stronger in overweight vs. weight-reduced states. We further hypothesized that associations between proxy indices and fat distribution would be similar to those between directly measured insulin sensitivity and fat distribution. Testing was performed in weight-stable conditions in 59 African-American (AA) and 62 white-American (WA) overweight, premenopausal women before and after a weight loss intervention. Subjects were retested 1 year following weight loss. Proxy indices were correlated against the insulin sensitivity index S I determined via minimal modeling. Fat distribution was assessed using computed tomography. Correlations between Si and proxy indices were consistently stronger among overweight women (r = 0.44-0.52) vs. weight-reduced women (r = 0.18-0.32), and among AA (r = 0.49-0.56, baseline; 0.24-0.36, weight-reduced) vs. WA (r = 0.38-0.46, baseline; 0.19-0.31, weight-reduced). Among subjects who regained >3 kg after 1 year, correlations between S I and proxy indices were similar to those observed at baseline, whereas correlations were weak among women who maintained their reduced body weight. S I and all proxy indices were similarly correlated with intra-abdominal adipose tissue (IAAT) at baseline, but not after weight loss. In conclusion, correlations between S I and proxy indices were affected by both ethnicity and weight status. If proxy indices are used in multiethnic populations, or in populations including both lean and overweight/obese subjects, data should be interpreted with caution.