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To examine the effect of an equivalent weight loss, by gastric bypass surgery (GBP) or by diet, on peptide YY3–36 (PYY3–36), ghrelin, and leptin levels and to determine the effect of diabetes status on PYY3–36 levels.The increased PYY3–36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery.Of the 30 morbidly obese women who participated in the study, 21 had type 2 diabetes mellitus, and were studied before and after equivalent weight loss of 10 kg by either GBP (n = 11) or by diet (n = 10).PYY3–36 levels were higher in obese diabetic as compared with nondiabetic individuals (64.1 ± 34.4 pg/mL vs. 39.9 ± 21.1 pg/mL; P < 0.05). PYY3–36 levels increased markedly in response to oral glucose after GBP (peak: 72.3 ± 20.5 pg/mL–132.7 ± 49.7 pg/mL; P < 0.001; AUC0–180: 51.5 ± 23.3 pg/mL.min−1–91.1 ± 32.2 pg/mL.min−1P < 0.001), but not after diet (peak: 85.5 ± 51.9 pg/mL–84.8 ± 41.13 pg/mL; P = NS; AUC0–180: 68.3 ± 38.5 pg/mL.min−1–61.1 ± 42.2 pg/mL.min−1P = NS). Fasting ghrelin levels increased after diet (425 ± 91 pg/mL–519 ± 105 pg/mL; P < 0.05), but did not change after GBP (506 ± 121 pg/mL–482 ± 196 pg/mL; P = NS).Diabetes status seems to be a determinant of PYY3–36 levels. GBP, but not diet-induced weight loss, resulted in markedly increased glucose-stimulated PYY3–36 levels. The increase in stimulated PYY3–36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss. Changes in PYY3–36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss.