Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: Mechanisms of Diabetes Remission and Role of Gut Hormones

Sep 24, 2013The Journal of clinical endocrinology and metabolism

How gastric bypass and sleeve surgery may lead to diabetes remission through gut hormones

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Abstract

In a study of 35 obese patients with type 2 diabetes, remission was observed in 13 after Roux-en-Y gastric bypass (RYGB) and in 7 after sleeve gastrectomy (SLG).

Both RYGB and SLG improved β-cell glucose sensitivity early and long term, but insulin sensitivity improved long term only.
Hormonal responses to meals varied, with RYGB showing increased glucagon and GLP-1 responses early post-surgery, while PP response decreased.
At one year, PYY levels increased while PP, amylin, ghrelin, and GLP-1 levels decreased after RYGB.
SLG produced similar hormonal changes to RYGB, except for an increased PP response and unchanged amylin levels.
In patients who achieved remission, fasting GLP-1 levels were higher, but their meal response was less pronounced compared to nonremitters.

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CONTEXT: In obese patients with type 2 diabetes (T2DM), Roux-en-Y-gastric-bypass (RYGB) and sleeve gastrectomy (SLG) improve glycemic control.

OBJECTIVE: The objective of this study was to investigate the mechanisms of surgery-induced T2DM improvement and role of gastrointestinal hormones. PATIENTS, SETTING, AND INTERVENTION: In 35 patients with T2DM, we performed a mixed-meal test before and 15 days and 1 year after surgery (23 RYGB and 12 SLG).

MAIN OUTCOME MEASURES: Insulin sensitivity, β-cell function, and amylin, ghrelin, PYY, pancreatic polypeptide (PP), glucagon, and glucagon-like peptide-1 (GLP-1) responses to the meal were measured.

RESULTS: T2DM remission occurred in 13 patients undergoing RYGB and in 7 patients undergoing SLG. Similarly in the RYGB and SLG groups, β-cell glucose sensitivity improved both early and long term (P < .005), whereas insulin sensitivity improved long term only (P < .006), in proportion to body mass index changes (P < .001). Early after RYGB, glucagon and GLP-1 responses to the meal increased, whereas the PP response decreased. At 1 year, PYY was increased, and PP, amylin, ghrelin, and GLP-1 were reduced. After SLG, hormonal responses were similar to those with RYGB except that PP was increased, whereas amylin was unchanged. In remitters, fasting GLP-1 was higher (P = .04), but its meal response was flat compared with that of nonremitters; postsurgery, however, the GLP-1 response was higher. Other hormone responses were similar between the 2 groups. In logistic regression, presurgery β-cell glucose sensitivity (positive, P < .0001) and meal-stimulated GLP-1 response (negative, P = .004) were the only predictors of remission.

CONCLUSIONS: RYGB and SLG have a similar impact on diabetes remission, of which baseline β-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

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Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: Mechanisms of Diabetes Remission and Role of Gut Hormones

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