Postprandial plasma GLP-1 levels are elevated in individuals with postprandial hypoglycaemia following Roux-en-Y gastric bypass - a systematic review

Abstract

Background and aims: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined.

Materials and methods: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA_1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ² estimate and I² statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias.

Results: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA_1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ² = 0.2, I² = 54.3. No publication bias was evident.

Conclusion: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA_1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515.

Keywords: Bariatric surgery; Glucagon-like peptide-1; Hypoglycaemia; Incretin; Metabolic surgery; Postprandial.