Faculty Peer Reviewed
The lifetime risk of developing diabetes for persons born in 2000 is around 35% and the NHANES database has suggested a greater than fourfold increase in prevalence over the last three generations. While bariatric surgery has become the most effective treatment for obesity, it has also been found to be an extremely effective treatment for type 2 diabetes. It was initially thought that the weight loss experienced by patients after bariatric surgery was responsible for improved glycemic control. However, patients experience improvement after only a few days, suggesting that hormonal changes are partly responsible. Discovering exactly which hormones are involved and how they “cure” diabetes has proven difficult.
The major players seem to be the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP); peptide YY (PYY); and ghrelin. GLP-1 is secreted by the L cells of the distal ileum in response to ingested nutrients, and acts as a potent insulin secretagogue. It has also been shown to slow gastric emptying and induce satiety in the central nervous system. GLP-1 increases lipogenesis in adipocytes and glycogenesis in liver cells and skeletal muscle.
GIP is secreted by the K cells of the duodenum and jejunum in response to carbohydrate and fat intake, and acts on pancreatic beta cells as an insulin secretagogue. However, it has no effect on gastric emptying or satiety. Like GLP-1, PYY is secreted by the L cells of the ileum, increases satiety, and slows gastric emptying through binding of receptors in the central and peripheral nervous systems.
Ghrelin is a hormone secreted by cells in the gastric fundus and proximal gut that acts on the hypothalamus to stimulate appetite and food intake, as well as decrease energy expenditure and fat catabolism. Serum ghrelin levels are high before a meal to stimulate appetite and decrease afterward. Ghrelin also acts in a paracrine manner in the pancreas to inhibit insulin secretion. Serum ghrelin levels are inversely proportional to body weight, while weight loss causes increased ghrelin levels , both of which suggest that ghrelin is important in maintaining body weight at a “set point.”
The hypothesis that the caloric restriction induced by bariatric surgery is responsible for improved blood glucose levels does not explain why bypass procedures have better diabetes remission rates than restrictive procedures. Moreover, bypass procedures cause remission in a few days, but remission doesn’t occur until months after laparoscopic gastric banding (LAGB).
There are two theories, both supported by studies of surgical procedures conducted on mice, to explain the rapid improvement in glucose metabolism following bypass procedures. In the hindgut hypothesis, rapid delivery of nutrients to the distal bowel increases secretion of GLP-1 and PYY, thus increasing glucose-dependent insulin secretion. The foregut theory, in contrast, suggests that causing food to bypass the duodenum and the jejunum prevents secretion of an unidentified “putative signal” that contributes to insulin resistance and type 2 diabetes.
Consistent with the hindgut theory, GLP-1 levels increase as much as threefold soon after bypass, but not after gastric banding, and PYY has been shown to increase as soon as two days after bypass. The effect of LAGB and bypass on GIP secretion is not as well understood, though studies have shown decreased levels two weeks after bypass. This makes sense physiologically, as GIP is secreted by cells in the proximal gut that would be bypassed by the procedure. Ghrelin levels after gastric bypass are more variable, and seem to be based on surgical technique. The amount of residual ghrelin-producing tissue and vagal innervation seem to determine the post-operative levels.
As more about the hormonal changes seen after bypass and gastric banding is learned, it becomes clear that it is not simply weight loss that causes improvements in glucose tolerance. Gastric banding is an effective treatment for diabetes; thus, more research should be done to assess its safety in patients with diabetes who are not obese. Further studies of patients after bariatric surgery will continue to elucidate the pathophysiologic mechanisms involved in diabetes. Based on these studies, medications can be created that mimic the effects of bypass in the body to treat diabetes effectively without an invasive surgical procedure.
Amy Dinitz is a 4th year medical student at NYU School of Medicine
Reviewed by Manish Parikh, MD, Assistant Professor, Bariatric Surgery, NYU Langone Medical Center
Image courtesy of Wikimedia Commons
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