Effects of Proximal Gut Bypass on Glucose Tolerance and Insulin Sensitivity in Humans

Roux-en-Y gastric bypass (RYGB) surgery produces a significant improvement in glucose metabolism prior to substantial weight loss; this is proposed to result from an enhanced incretin effect secondary to bypass of the duodenum and proximal jejunum. However, the caloric restriction that occurs early after surgery also has beneficial metabolic effects. To dissect the contribution of nutrient bypass of the proximal gut to improved glucose tolerance after RYGB surgery from caloric restriction, we induced a “non-surgical, proximal gut bypass” by directly administering a glucose load to the jejunum via a nasally inserted feeding tube.We studied 10 obese participants (BMI = 41.3 ± 7.4 kg/m2; 36 ± 9 years; 60% female; HbA1c = 5.5 ± 0.5%) on two occasions. At each visit, a 50-g glucose load was administered to either the stomach or proximal jejunum in random order. Blood was sampled −10, 0, 2, 4, 6, 8, …