Effects of Ingestion Routes on Hormonal and Metabolic Profiles in Gastric-Bypassed Humans

Context: Gastric bypass surgery (GBP) results in the rapid resolution of type 2 diabetes. Most studies aiming to explain the underlying mechanisms are limited to data obtained after a postsurgical recovery period, making assessment of confounding influences from, for example, weight loss and altered nutrient intake difficult. Objective: To examine the impact of GBP on hormonal and metabolite profiles under conditions of identical nutrient intake independent of weight loss, we studied GBP patients fitted with a gastrostomy tube to enable the administration of nutrients to bypassed segments of the gut. Thus, this model allowed us to simulate partially the preoperative condition and compare this with the postoperative situation in the same patient. Design: Patients (n = 4) were first given a mixed meal test (MMT) orally and then via the gastrostomy tube, preceded by overnight and 2-hour fasting, respectively. Blood samples were assessed for hormones and metabolites. Results: The oral MMT yielded 4.6-fold increase in plasma insulin (P < .05), 2-fold in glucagon-like peptide-1 (P < .05), and 2.5-fold in glucose-dependent insulinotropic peptide (P < .05) plasma levels, compared with the gastrostomy MMT. The changes in hormone levels were accompanied by elevated branched-chain amino acid levels (1.4-2-fold, P < .05) and suppressed fatty acid levels (similar to 50%, P < .05). Conclusions: These data, comparing identical nutrient delivery, demonstrate markedly higher incretin and insulin responses after oral MMT than after gastric MMT, thereby providing a potential explanation for the rapid remission of type 2 diabetes observed after GBP. The simultaneous increase in branched-chain amino acid questions its role as a marker for insulin resistance.