title: Glycated lysine-141 in haptoglobin improves the diagnostic accuracy for type 2 diabetes mellitus in combination with glycated hemoglobin HbA1cand fasting plasma glucose.
abstract: BACKGROUND
  Recent epidemiological studies indicate that only 30-50% of undiagnosed type 2 diabetes mellitus (T2DM) patients are identified using glycated hemoglobin (HbA1c) and elevated fasting plasma glucose (FPG) levels. Thus, novel biomarkers for early diagnosis and prognosis are urgently needed for providing early and personalized treatment.
  
  
  METHODS
  Here, we studied the glycation degrees of 27 glycation sites representing nine plasma proteins in 48 newly diagnosed male T2DM patients and 48 non-diabetic men matched for age (range 35-65 years). Samples were digested with trypsin and enriched for glycated peptides using boronic acid affinity chromatography. Quantification relied on mass spectrometry (multiple reaction monitoring) using isotope-labelled peptides as internal standard.
  
  
  RESULTS
  The combination of glycated lysine-141 of haptoglobin (HP K141) and HbA1cprovided a sensitivity of 94%, a specificity of 98%, and an accuracy of 96% to identify T2DM. A set of 15 features considering three glycation sites in human serum albumin, HP K141, and 11 routine laboratory measures of T2DM, metabolic syndrome, obesity, inflammation, and insulin resistance provided a sensitivity of 98%, a specificity of 100%, and an accuracy of 99% for newly diagnosed T2DM patients.
  
  
  CONCLUSIONS
  Our studies demonstrated the great potential of glycation sites in plasma proteins providing an additional diagnostic tool for T2DM and elucidating that the combination of these sites with HbA1cand FPG could improve the diagnosis of T2DM.
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.|Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Sandro
authors.initials: S
authors.lastname: Spiller
authors.affiliation: School of Electrical Engineering and Computer Science, Ohio University, Athens, OH USA.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department for Internal Medicine, Clinic for Endocrinology and Nephrology, University Hospital Leipzig, Universität Leipzig, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: School of Electrical Engineering and Computer Science, Ohio University, Athens, OH USA.
authors.forename: Lonnie
authors.initials: L
authors.lastname: Welch
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.|Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
keywords: Biomarker; Fasting plasma glucose (FPG); Glycation sites; HbA1c; Multiple reaction monitoring (MRM); Plasma proteins; Protein glycation; Type 2 diabetes mellitus