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Review
. 2018 Sep 10:9:530.
doi: 10.3389/fendo.2018.00530. eCollection 2018.

Weight-Independent Mechanisms of Glucose Control After Roux-en-Y Gastric Bypass

Blandine Laferrère  1 , François Pattou  2   3
Affiliations
Review

Weight-Independent Mechanisms of Glucose Control After Roux-en-Y Gastric Bypass

Blandine Laferrère et al. Front Endocrinol (Lausanne). .

Abstract

Roux-en-Y gastric bypass results in large and sustained weight loss and resolution of type 2 diabetes in 60% of cases at 1-2 years. In addition to calorie restriction and weight loss, various gastro-intestinal mediated mechanisms, independent of weight loss, also contribute to glucose control. The anatomical re-arrangement of the small intestine after gastric bypass results in accelerated nutrient transit, enhances the release of post-prandial gut hormones incretins and of insulin, alters the metabolism and the entero-hepatic cycle of bile acids, modifies intestinal glucose uptake and metabolism, and alters the composition and function of the microbiome. The amelioration of beta cell function after gastric bypass in individuals with type 2 diabetes requires enteric stimulation. However, beta cell function in response to intravenous glucose stimulus remains severely impaired, even in individuals in full clinical diabetes remission. The permanent impairment of the beta cell may explain diabetes relapse years after surgery.

Keywords: beta cell function; bile acids; gastric bypass surgery; glucagon-like peptide 1 (GLP-1); microbiome; sodium glucose transporter 1 (SGLt1); type 2 diabetes.

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Figures

Figure 1
Figure 1
Schematic representation of anatomical changes after RYGB.
Figure 2
Figure 2
Mechanistic model of improved glycemia after RYGB. RYGB improves glucose metabolism via weight loss, and via weight-independent mechanisms, including stimulation of gut peptides, alteration of bile acids enterohepatic cycle, remodeling of the gastrointestinal track, and alteration of the microbiome. Solid lines: evidence based mechanisms; dashed lines: possible mechanisms. RYGB, Roux-en-Y gastric bypass surgery; HGP, hepatic glucose production; BA derivation, bile acids derivation; GI, gastro intestinal; GNG, gluconeogenesis; GLP-1, glucagon-like-peptide 1; PYY, peptide YY; OXY, oxyntomodulin; GSIS, glucose-stimulated insulin secretion; PPG, post-prandial glucose; ↑: increase; ↓: decrease.
See this image and copyright information in PMC

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