The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study

Abstract

Objective: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.

Research design and methods: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.

Results: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.

Conclusions: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

© 2021 by the American Diabetes Association.

Figures

Figure 1

Schematic drawing of the standard limb and the long limb RYGB including the median small intestinal lengths as measured intraoperatively.

Figure 2

GLP-1, glucose, and insulin responses during the mixed meal tolerance test. Data are plotted as means ± SD. A mixed effects model analysis with Bonferroni adjustment was used for multiple comparisons. Stars in blue and red indicate statistical significance in the within-group comparison of the standard limb and long limb groups, respectively, to baseline. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 3

Measures of hepatic and peripheral insulin sensitivity during the euglycemic hyperinsulinemic clamp. Ra at the low-dose insulin infusion (measure of hepatic insulin sensitivity) and Rd at the high-dose insulin infusion (measure of peripheral insulin sensitivity. Data are plotted as means ± SD. N = 23 in each group. A mixed effects model analysis with Bonferroni adjustment was used for multiple comparisons. Stars in blue and red indicate statistical significance in the within-group comparison of the standard limb and long limb groups, respectively, to baseline. *P < 0.05, **P < 0.01, ***P < 0.001.