To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux‐en‐Y gastric bypass (RYGB) and specifically the contribution of the concurrent peri‐operative dietary restrictions, which may also alter glucose metabolism.

In order to assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled 10 patients with type 2 diabetes scheduled to undergo RYGB. All patients underwent a 10‐day inpatient supervised dietary intervention equivalent to the peri‐operative diet (diet‐only period), followed by, after a re‐equilibration (washout) period, an identical period of pair‐matched diet in conjunction with RYGB (diet and RYGB period). We conducted extensive metabolic assessments during a 6‐hour mixed‐meal challenge test, with stable isotope glucose tracer infusion performed before and after each intervention.

Similar improvements in glucose levels, β‐cell function, insulin sensitivity and post‐meal hepatic insulin resistance were observed with both interventions. Both interventions led to significant reductions in fasting and postprandial acyl ghrelin. The diet‐only intervention induced greater improvements in basal hepatic glucose output and post‐meal gastric inhibitory polypeptide (GIP) secretion. The diet and RYGB intervention induced significantly greater increases in post‐meal glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY) and glucagon levels.

Strict peri‐operative dietary restriction is a main contributor to the rapid improvement in glucose metabolism after RYGB. The RYGB‐induced changes in the incretin hormones GLP‐1 and PYY probably play a major role in long‐term compliance with such major dietary restrictions through central and peripheral mechanisms.