INTRODUCTION: Obesity is associated with insulin resistance (IR) and diabetes (DM). Some obese individuals, however, have normal insulin-glucose metabolism. While gastric bypass (GB) cures IR and DM, its effects on normal physiology have not been described; in addition, there are reports of postoperative pathological hypoglycemia. We studied IR and beta-cell sensitivity for patients undergoing gastric bypass. METHODS: 123 patients undergoing GB had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Twenty nine (24%) patients with DM were excluded from this analysis. Homeostasis model of assessment was used to estimate IR (HOMA-IR) and beta-cell sensitivity (HOMA-B). Patients were categorized with IR if HOMA-IR > 3.6. HOMA-B of 100 signified normal beta-cell sensitivity. Student’s t-test was used to determine whether differences were significant. RESULTS: Adipose mass, as estimated by BMI, did not correlate with IR. Forty three (35%) patients had IR. Correction of IR for this group occurred by 12 days postoperatively. Fifty one (41%) patients did not have IR, with normal HOMA-IR and HOMA-B preoperatively. They demonstrated an increase of beta-cell sensitivity by 12 days postoperatively, which corrected by six-months. Major alterations in HOMA-IR or HOMA-B occurred by 12 days, after which the IR and non-IR groups mirrored each other. CONCLUSIONS: Adipose mass, in and of itself, does not lead to IR. Severely obese individuals can be categorized as insulin resistant or non-insulin resistant, and the effect of GB depends upon this preoperative physiology; IR decreases in the former and beta-cell sensitivity increases in the latter. Metabolic characterization of patients is imperative in order to determine preoperative risk of obesity and assess outcomes following GB.