GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass
- Department of Internal Medicine II, Clinical Research Unit, Clinical Center of the Ludwig-Maximilians University, Campus Grosshadern, Munich, Germany
- Corresponding author: Jörg Schirra, .
The worldwide increase in obesity is associated with a higher prevalence of type 2 diabetes (T2D), and severe obesity occurs with the greatest risk (1). Bariatric surgery is currently the most effective treatment not only for weight loss but also for prevention or treatment of T2D in such patients (2). It leads to remission or improvement of T2D in the majority of morbidly obese (3,4). Roux-en-Y gastric bypass (RYGB) is one of the most frequently performed procedures. With RYGB, the stomach is reduced to a small proximal pouch (30–50 mL) and anastomosed to the jejunum, thereby bypassing the majority of the stomach and duodenum. After RYGB, T2D improves rapidly often before significant weight loss occurs. The mechanisms behind this phenomenon are not clearly resolved. Caloric restriction contributes. Extreme caloric restriction to the limit just tolerated in patients after surgery improved insulin resistance in obese subjects similarly as found in after the first week after RYGB (5). Of interest, the malabsorptive component of the RYGB procedure approximately accounts only for up to 11% of the total reduction in combustible energy absorption (6). Changes of adipokine-induced inflammation and insulin resistance (7) and reduction of branched-chain amino acids correlating with insulin resistance (8) have been proposed as further mechanisms operating after bariatric surgery complementing the sole weight loss.
A popular hypothesis points to an antidiabetic effect after RYGB of postprandially exaggeratedly released gut peptides, such as glucagon-like peptide 1 (GLP-1), already starting early after surgery. The release of GLP-1 depends on gastric emptying (GE) velocity (9). It lowers postprandial glycemia by stimulation of insulin, inhibition of glucagon secretion, and delay of GE. For example, …