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Energy restriction and Roux-en-Y gastric bypass reduce postprandial ?-dicarbonyl stress in obese women with type 2 diabetes.

ABSTRACT: Dicarbonyl compounds are formed as byproducts of glycolysis and are key mediators of diabetic complications. However, evidence of postprandial ?-dicarbonyl formation in humans is lacking, and interventions to reduce ?-dicarbonyls have not yet been investigated. Therefore, we investigated postprandial ?-dicarbonyl levels in obese women without and with type 2 diabetes. Furthermore, we evaluated whether a diet very low in energy (very low calorie diet [VLCD]) or Roux-en-Y gastric bypass (RYGB) reduces ?-dicarbonyl stress in obese women with type 2 diabetes.In lean (n?=?12) and obese women without (n?=?27) or with type 2 diabetes (n?=?27), we measured the ?-dicarbonyls, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and glucose in fasting and postprandial plasma samples obtained during a mixed meal test. Obese women with type 2 diabetes underwent either a VLCD or RYGB. Three weeks after the intervention, individuals underwent a second mixed meal test.Obese women with type 2 diabetes had higher fasting and particularly higher postprandial plasma ?-dicarbonyl levels, compared with those without diabetes. After three weeks of a VLCD, postprandial ?-dicarbonyl levels in diabetic women were significantly reduced (AUC MGO -14%, GO -16%, 3-DG -25%), mainly through reduction of fasting plasma ?-dicarbonyls (MGO -13%, GO -13%, 3-DG -33%). Similar results were found after RYGB.This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma ?-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive ?-dicarbonyls in obese individuals with type 2 diabetes.ClinicalTrials.gov NCT01167959.

SUBMITTER: Maessen DE

PROVIDER: S-EPMC4969347 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Energy restriction and Roux-en-Y gastric bypass reduce postprandial α-dicarbonyl stress in obese women with type 2 diabetes.

Maessen Dionne E DE Hanssen Nordin M NM Lips Mirjam A MA Scheijen Jean L JL Willems van Dijk Ko K Pijl Hanno H Stehouwer Coen D CD Schalkwijk Casper G CG

Diabetologia 20160616 9

<h4>Aims/hypothesis</h4>Dicarbonyl compounds are formed as byproducts of glycolysis and are key mediators of diabetic complications. However, evidence of postprandial α-dicarbonyl formation in humans is lacking, and interventions to reduce α-dicarbonyls have not yet been investigated. Therefore, we investigated postprandial α-dicarbonyl levels in obese women without and with type 2 diabetes. Furthermore, we evaluated whether a diet very low in energy (very low calorie diet [VLCD]) or Roux-en-Y g ...[more]

PMID: 27312699

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Project description:Background and aimsBariatric 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 methodsThe 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.ResultsFrom 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.ConclusionFollowing 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.

Dataset Information

Energy restriction and Roux-en-Y gastric bypass reduce postprandial ?-dicarbonyl stress in obese women with type 2 diabetes.

Publications

Energy restriction and Roux-en-Y gastric bypass reduce postprandial α-dicarbonyl stress in obese women with type 2 diabetes.

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