Glycated lysine-141 in haptoglobin improves the diagnostic accuracy for type 2 diabetes mellitus in combination with glycated hemoglobin HbA1c and fasting plasma glucose

Abstract

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 HbA1c provided 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 HbA1c and FPG could improve the diagnosis of T2DM.

Keywords

• Biomarker
• Fasting plasma glucose (FPG)
• Glycation sites
• HbA1c
• Multiple reaction monitoring (MRM)
• Plasma proteins