The “hindgut hypothesis” raised by Cummings et al 24 suggests that accelerated transit of concentrated nutrients (particularly glucose) to the distal intestine results in increased production of insulinotropic and appetite-controlling substances, which account for the reversal of hyperglycemia and obesity.
In contrast, the “foregut hypothesis” raised by Rubino et al 28 suggests that nutrient interactions in the duodenum are diabetogenic and, hence, bypassing the duodenum would reverse this defect. Their conclusions come from experiments in rodents that underwent jejunoileal bypass and subsequent refeeding through the bypassed intestine.
GUT HORMONES AND OTHER PEPTIDES ALTERED BY BARIATRIC SURGERY
Incretin hormones: GLP-1, GIP
Gastrointestinal hormones that increase insulin release after a meal are known as incretins. Of interest, they have this effect only when glucose is ingested orally—not when it is infused intravenously. 29,30
Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) account for 50% to 60% of nutrient-related insulin secretion. In addition to stimulating insulin, GLP-1 suppresses glucagon and slows gastric emptying, which delays digestion and reduces postprandial glycemia. GLP-1 also acts on the hypothalamus to induce satiety.
Laferrère et al 31 and others 32,33 documented robust increases in postprandial levels of GLP-1 within 4 weeks after Roux-en-Y surgery. GLP-1 levels did not increase with comparable weight loss induced by diet.
Rubino et al 28,34 documented similar findings that occurred prior to marked weight loss, suggesting that the benefit of Roux-en-Y surgery on remission of diabetes may not be completely attributable to reduced caloric intake and weight loss. Insulin secretion is generally reduced after gastric restrictive procedures (eg, laparoscopic adjustable gastric banding) and biliopancreatic diversion, 35 and is increased after Roux-en-Y gastric bypass. 32,33,36
Noninsulinotropic peptides: Ghrelin, peptide YY
Noninsulinotropic gut peptides that are altered after Roux-en-Y surgery include ghrelin and peptide YY.
Ghrelin, a hormone derived from the gastric fundus, stimulates appetite. Ghrelin concentrations are lower after Roux-en-Y surgery, indicating that suppression of hunger signals helps sustain weight loss. In contrast, ghrelin levels increase with diet-induced weight loss. 37 However, the data on ghrelin levels at various times after bariatric surgical procedures are not consistent. 33,38
Peptide YY, like GLP-1, is secreted by L cells of the distal small intestine and is responsible for increasing satiety and delaying gastric emptying after meals. Numerous studies have consistently documented increases in postprandial peptide YY and GLP-1 levels after gastric bypass. 32,33,39–41
ACUTE EFFECTS OF BARIATRIC SURGERY ON INSULIN SECRETION, SENSITIVITY
Bariatric surgery alters both insulin secretion and insulin sensitivity, thus improving glucose regulation.
The relationship between insulin secretion and sensitivity is a hyperbolic curve, so that any change in insulin sensitivity is balanced by a reciprocal and proportionate change in insulin secretion. The development of type 2 diabetes is characterized by a reduction in insulin secretion (decompensation) relative to the severity of insulin resistance.
In the first 6 weeks after Roux-en-Y gastric bypass or biliopancreatic diversion, insulin sensitivity improves while insulin secretion increases disproportionately, associated with a robust increase in GLP-1, and resulting in normal glucose homeostasis. 16,31,42