Ghrelin levels increase before and decrease after meals, potentially playing a role in meal initiation and satiety in an inverse pattern to that of insulin. The role of ghrelin in childhood obesity, a state associated with hyperinsulinism and insulin resistance, is not fully understood. Therefore, the aims of the present study were to investigate the dynamics of ghrelin suppression after an oral glucose tolerance test (OGTT) in normal weight (NW) vs overweight (OW) children and the relationship of ghrelin suppression to insulin sensitivity. Thirty-seven NW (15 males and 22 females; 9.4 +/- 0.2 yr old) and 23 OW (13 males and 10 females; 9.4 +/- 0.3 yr old) prepubertal children underwent a 3-h OGTT with measurements of ghrelin, glucose, and insulin. The fasting glucose to insulin ratio and the whole body insulin sensitivity index were used to assess the relationship of insulin sensitivity to fasting ghrelin and ghrelin response to the OGTT, respectively. Fasting ghrelin levels were significantly lower in OW vs NW youth and were mainly influenced by insulin sensitivity independent of adiposity. OGTT-induced absolute suppression in ghrelin was approximately 50% less in OW vs NW children, resulting in a similar percent suppression from baseline in the two groups despite a significantly higher insulin response in OW. The suppression of ghrelin correlated positively with the whole body insulin sensitivity index (r = 0.43; P = 0.001) and negatively with the change in insulin at 30 min (r = -0.31; P = 0.02). Fasting ghrelin, the change in insulin, and the change in glucose during the OGTT were the significant independent variables contributing to the variance in absolute suppression of ghrelin (r2 = 0.42; P < 0.001). Only the change in glucose contributed significantly to the variance in the percent suppression of ghrelin (r2 = 0.14; P = 0.019). Fasting ghrelin and ghrelin suppression after OGTT are modulated by insulin sensitivity. Alterations in ghrelin suppression in OW children may be yet another manifestation of the insulin resistance of obesity. Whether this is responsible for differences in satiety in OW individuals merits additional investigation.