Going With the Flow: Adaptation of β-Cell Function to Glucose Fluxes After Bariatric Surgery
- 1Department of Medicine, Division of Endocrinology, University of Cincinnati, Cincinnati, Ohio
- 2Cincinnati VA Medical Center, Cincinnati, Ohio.
- Corresponding author: David A. D’Alessio, .
Roux-en-Y gastric bypass (RYGB) surgery induces remission of type 2 diabetes (T2D) at higher rates than restrictive bariatric surgeries (1) or intensive medical treatment (2). While weight loss induced by lifestyle interventions or bariatric surgery improves glucose tolerance gradually by enhancing insulin sensitivity (3–5), some of the antidiabetic effect of RYGB is immediate and independent of the amount of weight loss (5–7). The dramatic resolution of diabetes after RYGB is consistent with processes rapidly engaged by the restructured gastrointestinal system to alter postprandial glucose regulation.
Individuals with RYGB have larger postprandial glucose excursions, with higher and earlier peaks and lower glucose nadirs, as early as 1 week after surgery (7). In parallel with this change in glycemia, meal ingestion shifts the postprandial insulin response upward and to the left (7), with more rapid insulin secretion over a shorter period. It is not clear to what extent the increased β-cell secretion is a response to greater glycemic stimulus or whether other factors are at play. There is experimental support for greater stimulation by gastrointestinal hormones, especially glucagon-like peptide 1 (8), and neural inputs to the β-cell (9) following RYGB are increased. Regardless of the underlying mechanism, a majority of patients with T2D benefit from RYGB in the short term, and the enhanced insulin response is thought to contribute significantly to this outcome. Interestingly, beneficial effects of surgery on β-cell function are more difficult to ascertain in nondiabetic subjects after RYGB, since many measures of insulin secretion are actually diminished over time as insulin sensitivity improves (10). It is now apparent that RYGB also has a significant impact on glucagon secretion. The notable feature after surgery is …