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

      Iqbal, Zohaib; email: zohaib@doctors.org.uk; Fachim, Helene A.; email: helene.fachim@manchester.ac.uk; Gibson, J. Martin; email: martin.gibson@manchester.ac.uk; Baricevic-Jones, Ivona; email: ivona.baricevic-jones@manchester.ac.uk; Campbell, Amy E.; email: amy.campbel@manchester.ac.uk; Geary, Bethany; orcid: 0000-0002-5592-5532; email: bethany.geary@manchester.ac.uk; Donn, Rachelle P.; orcid: 0000-0001-6976-9828; email: Rachelle.donn@manchester.ac.uk; Hamarashid, Dashne; email: hamarashiddashne@gmail.com; Syed, Akheel; orcid: 0000-0001-8696-7121; email: akheel.syed@manchester.ac.uk; Whetton, Anthony D.; orcid: 0000-0002-1098-3878; email: tony.whetton@manchester.ac.uk; et al. (MDPI, 2021-08-18)
      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.