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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

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posted on 06.11.2020, 21:42 by Alexander Dimitri Miras, Anna Kamocka, Belén Pérez-Pevida, Sanjay Purkayastha, Krishna Moorthy, Ameet Patel, Harvinder Chahal, Gary Frost, Paul Bassett, Lidia Castagnetto-Gissey, Lucy Coppin, Nicola Jackson, Anne Margot Umpleby, Stephen Robert Bloom, Tricia Tan, Ahmed Rashid Ahmed, Francesco Rubino
Objective

Roux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial 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 hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial 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

Fifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.

Results

Both groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.

Conclusion

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.

Funding

This research was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation programme. Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre, the NIHR Imperial Clinical Research Facility and NIHR King’s Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The Section of Endocrinology and Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and is supported by the NIHR Biomedical Research Centre Funding Scheme.

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