Abstract
Given the availability of human studies of the relatively specific and potent glucagon-like peptide (GLP)-1 receptor antagonist exendin (Ex) 9–39, it was just a question of time for the first study of GLP-1 receptor blockade after gastric bypass surgery to appear. In this issue of Diabetes , Salehi et al. (1) report such studies in two groups of individuals previously operated on for obesity with Roux-en-Y gastric bypass (RYGB) surgery: one asymptomatic group and one control group with recurrent hypoglycemia after the operation. The background is that these operations not only bring about a massive weight loss (reductions in BMI from 52 to 33/32 kg/m2 in the current study), but also bring about resolution of type 2 diabetes, if present, in a high percentage (80–90%) of patients. In the current study, three of twelve individuals in both operated groups had type 2 diabetes before the operation, which was resolved completely in all cases. RYGB was originally conceived as a restrictive and malabsorptive procedure, but actually it is neither. The normal function of the stomach is to retain and process food stuff until allowing a controlled emptying precisely adjusted to the digestive capacity of the proximal intestine. The reservoir is lost after the operation and, in effect, a straight tube is constructed that allows unimpeded passage of ingested nutrients directly to the alimentary limb of the Y-anastomosis and directly onwards to the “common limb,” where nutrients are admixed with digestive secretions and digestion starts. This is nicely illustrated in studies of acetaminophen absorption, which proceeds at a maximal rate immediately upon meal ingestion without the slightest retardation (2). Furthermore, balance studies have documented that there is no malabsorption of macronutrients after RYGB (3 …
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