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Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery.

ABSTRACT: Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass (n = 7) or sleeve gastrectomy (n = 3). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was done on samples taken at 4 months before (baseline) and 6 and 12 months after BS. Four hundred sixty-seven proteins were quantified by SWATH-MS. Principal component analysis resolved samples from distinct time points after selection of key discriminatory proteins: 25 proteins were differentially expressed between baseline and 6 months post-surgery; 39 proteins between baseline and 12 months. Eight proteins (SHBG, TF, PRG4, APOA4, LRG1, HSPA4, EPHX2 and PGLYRP) were significantly different to baseline at both 6 and 12 months post-surgery. The panel of proteins identified as consistently different included peptides related to insulin sensitivity (SHBG increase), systemic inflammation (TF and HSPA4-both decreased) and lipid metabolism (APOA4 decreased). We found significant changes in the proteome for eight proteins at 6- and 12-months post-BS, and several of these are key components in metabolic and inflammatory pathways. These may represent potential biomarkers of remission of T2DM.

SUBMITTER: Iqbal Z

PROVIDER: S-EPMC8396849 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale & objectiveThe association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations.Study designProspective observational study.Study participants737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years.PredictorsDemographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides.OutcomesEstimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes.Analytical approachLinear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission.ResultsRemission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD.LimitationsA minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results.ConclusionsRemission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes.

Project description:AIM:To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. METHODS:A total of 40 adults [mean ± sd body mass index 36 ± 3 kg/m(2) , age 48 ± 9 years, glycated haemoglobin (HbA1c) 9.7 ± 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-?, high-sensitivity C-reactive protein (hs-CRP)] were also assessed. RESULTS:At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and ?-cell function (C-peptide0-120 /glucose0-120 × Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced ?-cell function, lower triglyceride levels and fat loss. CONCLUSIONS:Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key to achieving higher type 2 diabetes remission rates after bariatric surgery.

Project description:BackgroundAlthough bariatric surgery is an effective treatment for type 2 diabetes (T2D) in patients with morbid obesity, further studies are needed to evaluate factors influencing the chance of achieving diabetes remission. The objective of the present study was to investigate the association between T2D duration and the chance of achieving remission of T2D after bariatric surgery.Methods and findingsWe conducted a nationwide register-based cohort study including all adult patients with T2D and BMI ≥ 35 kg/m2 who received primary bariatric surgery in Sweden between 2007 and 2015 identified through the Scandinavian Obesity Surgery Registry. The main outcome was remission of T2D, defined as being free from diabetes medication or as complete remission (HbA1c < 42 mmol/mol without medication). In all, 8,546 patients with T2D were included. Mean age was 47.8 ± 10.1 years, mean BMI was 42.2 ± 5.8 kg/m2, 5,277 (61.7%) were women, and mean HbA1c was 58.9 ± 17.4 mmol/mol. The proportion of patients free from diabetes medication 2 years after surgery was 76.6% (n = 6,499), and 69.9% at 5 years (n = 3,765). The chance of being free from T2D medication was less in patients with longer preoperative duration of diabetes both at 2 years (odds ratio [OR] 0.80/year, 95% CI 0.79-0.81, p < 0.001) and 5 years after surgery (OR 0.76/year, 95% CI 0.75-0.78, p < 0.001). Complete remission of T2D was achieved in 58.2% (n = 2,090) at 2 years, and 46.6% at 5 years (n = 681). The chance of achieving complete remission correlated negatively with the duration of diabetes (adjusted OR 0.87/year, 95% CI 0.85-0.89, p < 0.001), insulin treatment (adjusted OR 0.25, 95% CI 0.20-0.31, p < 0.001), age (adjusted OR 0.94/year, 95% CI 0.93-0.95, p < 0.001), and HbA1c at baseline (adjusted OR 0.98/mmol/mol, 95% CI 0.97-0.98, p < 0.001), but was greater among males (adjusted OR 1.57, 95% CI 1.29-1.90, p < 0.001) and patients with higher BMI at baseline (adjusted OR 1.07/kg/m2, 95% CI 1.05-1.09, p < 0.001). The main limitations of the study lie in its retrospective nature and the low availability of HbA1c values at long-term follow-up.ConclusionsIn this study, we found that remission of T2D after bariatric surgery was inversely associated with duration of diabetes and was highest among patients with recent onset and those without insulin treatment.

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Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery.

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