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 (HbA1c) 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). HbA1c 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 HbA1c 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.

Gut motility and hormone changes after bariatric procedures

“…Additionally, the study found that a shorter Roux limb length correlates with a greater increase in postprandial GLP-1 levels, potentially enhancing glycemic control postsurgery [17]. Interestingly, in another meta-analysis In a comparison of 12 studies involving patients who underwent RYGB, it was found that those with postsurgery hypoglycemia showed notably higher peak levels of GLP-1, insulin, and C-peptide, in contrast to those without hypoglycemia, whereas peak GIP and glucagon levels did not differ significantly between the groups [18]. In a meta-analysis of 28 studies with 653 participants, there was a notable increase in GLP-1 levels following LSG, corresponding with significant decreases in body mass index and substantial total body weight loss [12].…”

“…Lesser amounts of PYY are also produced in the pancreatic islets of Langerhans and the gigantocellular reticular nucleus in the rostral medulla [23,24]. PYY [3–10,11 ▪ ,12–18,19 ▪ ,20–35] is known for its significant appetite-suppressing effects [8]. Research in animals demonstrates that PYY's [3–10,11 ▪ ,12–18,19 ▪ ,20–35] interaction with the Y2 receptor leads to the deactivation of NPY/AgRP neurons and the activation of POMC neurons within the hypothalamus's arcuate nucleus.…”

“…PYY [3–10,11 ▪ ,12–18,19 ▪ ,20–35] is known for its significant appetite-suppressing effects [8]. Research in animals demonstrates that PYY's [3–10,11 ▪ ,12–18,19 ▪ ,20–35] interaction with the Y2 receptor leads to the deactivation of NPY/AgRP neurons and the activation of POMC neurons within the hypothalamus's arcuate nucleus. Additionally, PYY is involved in lowering plasma ghrelin levels and diminishing the responsiveness of arcuate nucleus neurons to ghrelin.…”

Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus

“…Another systemic review showed that following RYGB, individuals experiencing post-bariatric surgery hypoglycemia exhibit heightened GLP-1, insulin, and C-peptide in response to nutrients, with lower HbA1c levels. These findings propose that inhibiting GLP-1 could be a reasonable intervention to prevent hypoglycemia in patients dealing with post-bariatric surgery hypoglycemia following RYGB[ 88 ]. In addition, GLP-1 RAs showed a potential role in the remission of psoriasis, as noted in case reports following bariatric surgery, which opens up intriguing avenues for research and potential novel approaches to treating psoriasis[ 89 ].…”

Physiological Appetite Regulation and Bariatric Surgery

“…Studies that used GLP-1R antagonists corrected the underlying hypoglycaemia in symptomatic patients, suggesting a role for GLP-1 in the underlying pathophysiology [ 213 ]. In other studies following RYGB individuals with post-RYGB hypoglycaemia had greater postprandial GLP-1 and insulin concentrations but not GIP when compared with individuals who had the same bariatric surgery but did not develop hypoglycaemia [ 215 ]. One hypothesis, supported by cross-sectional studies, is that postprandial hyperinsulinemia after RYGB can be attributed to the combined effects of more rapid nutrient transit from the gastric pouch to the gut coupled with an increased incretin effect [ 214 , 216 ].…”