Among obesity-prone individuals, metabolic state may interact with diet in determining body composition. We tested the hypotheses that, among 103 weight-reduced women over 1 year, (i) insulin sensitivity would be positively associated with change in %fat; (ii) this association would be modulated by dietary glycemic load (GL); and (iii) changes in fat distribution would be related to indexes of glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and postchallenge insulin and glucose, and glucose tolerance were assessed during intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution were examined using dual-energy X-ray absorptiometry and computed tomography. Dietary GL was assessed on 67 women using food records. On average, women showed a +5.3 +/- 3.0% change in %fat over 1 year, with the magnitude of this change being greater in relatively insulin sensitive women (+6.0 +/- 0.4%, mean +/- s.e.m.) than in relatively insulin resistant women (+4.4 +/- 0.4 kg; P < 0.05). Women who were relatively insulin sensitive and who consumed a higher GL diet showed a +6.8 +/- 0.7% change in %fat, which was greater than those who were less insulin sensitive, regardless of diet (P < 0.05), but did not differ from women who were relatively insulin sensitive and who consumed a lower GL diet (P = 0.105). Changes in intra-abdominal and deep subcutaneous abdominal fat were inversely associated with the postchallenge decline in serum glucose. In conclusion, greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet. The potential association between indexes of glucose disposal and changes in fat distribution warrants further study.