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.

Highlights

  • Obesity is a chronic disease which in many cases requires complex management, while being recognized as the fastest growing problem affecting public health worldwide [1,2,3]

  • Different studies have shown that reductions in waist circumference after Bariatric surgery (BS) are associated with a greater probability of type 2 diabetes mellitus (T2DM) remission [13,14,15]

  • BS resulted in a significant reduction in body mass index (BMI) after 6- and 12-months (p < 0.0001), systolic and diastolic blood pressure after 12 months (p < 0.05) but not 6 months, HbA1c after 6- and 12-months (p < 0.0001)

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Summary

Introduction

Obesity is a chronic disease which in many cases requires complex management, while being recognized as the fastest growing problem affecting public health worldwide [1,2,3]. Obesity often has multiple predisposing and precipitating factors and is itself associated with a high mortality rate and with comorbid conditions such as type 2 diabetes mellitus (T2DM), metabolic syndrome, hypertension, dyslipidemia, several cancers [4], premature cell ageing [5], sleep apnea and osteoarthritis [6,7]. Bariatric surgery (BS) has been shown to be an effective therapy for weight loss, and improves a variety of metabolic parameters conferring protection from cardiovascular (CVD) and other diseases [9,10]. Immediate post-operative weight-independent effects combined with weight loss can result in remission of T2DM in up to 80% of patients [10]. Different studies have shown that reductions in waist circumference after BS are associated with a greater probability of T2DM remission [13,14,15]

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