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Effects of Roux-en-Y gastric bypass on fasting and postprandial levels of the inflammatory markers YKL-40 and MCP-1 in patients with type 2 diabetes and glucose tolerant subjects.

ABSTRACT: The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT).Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year) RYGB.Fasting state MCP-1 levels decreased after RYGB in both groups (P values < 0.0001) whereas fasting YKL-40 levels were unchanged (P values ? 0.120). Postprandial MCP-1 levels showed a tendency towards a decrease on most study days; however, the changes were only significant at 1 week (P = 0.001) and 1?yr (P < 0.0001) in the T2D group and at 3?mo after RYGB in the NGT group (P = 0.009). YKL-40 levels showed a slight, postprandial suppression on all study days in the T2D group (all P values ? 0.021).Fasting MCP-1 levels, but not YKL-40 levels, decrease after RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers are discrete and inconsistent.

SUBMITTER: Thomsen SB

PROVIDER: S-EPMC3835778 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Effects of Roux-en-Y gastric bypass on fasting and postprandial levels of the inflammatory markers YKL-40 and MCP-1 in patients with type 2 diabetes and glucose tolerant subjects.

Thomsen Stine Brinkløv SB Rathcke Camilla Noelle CN Jørgensen Nils Bruun NB Madsbad Sten S Vestergaard Henrik H

Journal of obesity 20131103

<h4>Background</h4>The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT).<h4>Methods</h4>Ten obese patients with T2D and 10 subjects with NGT were exam ...[more]

PMID: 24303210

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Project description:BACKGROUND:Obesity is characterized by low grade inflammation and an altered secretion of inflammatory cytokines from the adipose tissue. Weight loss has shown to reduce inflammation; however, changes in cytokine profiles during massive weight loss are not well described. The present study explored the hypothesis that Roux-en-Y gastric bypass (RYGB) reduces circulating levels of pro-inflammatory cytokines, while increasing anti-inflammatory cytokines in obese subjects with type 2 diabetes (T2D) and in obese normal glucose tolerant (NGT) subjects. METHODS:Thirteen obese subjects with T2D [weight; 129?±?14 kg, glycated hemoglobin (HbA1c); 7.0?±?0.9%, body mass index (BMI); 43.2?±?5.3 kg/m(2), mean?±?SD] and twelve matched obese NGT subjects [weight; 127?±?15 kg, HbA1c; 5.5?±?0.4%, BMI; 41.5?±?4.8 kg/m(2), mean?±?SD] were examined before, one week, three months, and one year after surgery. Interleukin (IL)-6, leptin, adiponectin, IL-8, transforming growth factor beta (TGF-?), and the incretin hormone glucagon-like peptide-1 (GLP-1) were measured in the fasting state and during a liquid meal. Insulin resistance was evaluated by HOMA-IR. RESULTS:Weight loss did not differ between the two groups. Before surgery, HbA1c was higher and HOMA-IR lower in T2D patients, however, converged to the values of NGT subjects one year after surgery. Circulating cytokine concentrations did not differ between the two groups at any time point. One week after surgery, circulating IL-6 and IL-8 were increased, while adiponectin and leptin were reduced compared with pre-surgical concentrations. Three months after surgery, IL-8 was increased, leptin was reduced, and no change was observed for IL-6, TGF-?, and adiponectin. One year after surgery, concentrations of IL-6, TGF-?, and leptin were significantly reduced compared to before surgery, while adiponectin was significantly increased. CONCLUSIONS:One year after RYGB, fasting concentrations of IL-6 and leptin were reduced, while no changes were observed in IL-8. TGF-? was decreased and adiponectin increased in both T2D and NGT obese subjects. This study is the first to examine IL-8 and TGF-? in obese subject after RYGB. Resolution of inflammation could offer a potential explanation for the health improvement associated with major weight loss after bariatric surgery. TRIAL REGISTRATION:http://www.clinicaltrials.gov (NCT01579981).

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.

Project description:To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1,000 patients undergoing Roux-en-y gastric bypass and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than one hundred thousand gene expression traits representing four metabolically relevant tissues; liver, omental adipose, subcutaneous adipose and stomach. We successfully identified 24,531 eSNPs corresponding to ~10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high quality disease map for each tissue in morbidly obese patients to not only inform genetic associations indentified in this cohort, but in previously published genome wide association studies as well. eSNPs and gene co-expression modules identification in morbidly obese patients represent a great resource that will aid in elucidating the key networks associated with morbid obesity, response to RYGB and disease as a whole. Keywords: Tissue profiling in a human cohort. Liver tissue was collected from patients at the time of RYGB surgery at Massachusetts General Hospital between 2000 and 2007. Samples were collected in RNAlater (Ambion/Applied Biosystems), stored at -80° and shipped to Rosetta Inpharmatics Gene Expression Laboratory Seattle, WA for extraction, amplification, labeling, and microarray processing. Samples processed ranged in size from 100-200mg. Total RNA extracted from liver was converted to fluorescently labeled cRNA that was hybridized to custom 44K DNA oligonucleotide microarrays manufactured by Agilent Technologies as described previously (Hughes et al. 2001; Schadt et al. 2008). Successful gene expression profiling results were collected from 651 liver samples.

Dataset Information

Effects of Roux-en-Y gastric bypass on fasting and postprandial levels of the inflammatory markers YKL-40 and MCP-1 in patients with type 2 diabetes and glucose tolerant subjects.

Publications

Effects of Roux-en-Y gastric bypass on fasting and postprandial levels of the inflammatory markers YKL-40 and MCP-1 in patients with type 2 diabetes and glucose tolerant subjects.

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