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Pharmaceuticals 2018, 11(2), 38; https://doi.org/10.3390/ph11020038

Diagnostic Accuracy of Protein Glycation Sites in Long-Term Controlled Patients with Type 2 Diabetes Mellitus and Their Prognostic Potential for Early Diagnosis

1
Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy and Center for Biotechnology Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany
2
School of Electrical Engineering and Computer Science, Ohio University, Stocker Center 354, Athens 45701, OH, USA
3
Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Liebigstr. 21, 04103 Leipzig, Germany
*
Authors to whom correspondence should be addressed.
Received: 3 April 2018 / Revised: 24 April 2018 / Accepted: 24 April 2018 / Published: 30 April 2018
(This article belongs to the Collection Choices of the Journal)
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Abstract

Current screening tests for type 2 diabetes mellitus (T2DM) identify less than 50% of undiagnosed T2DM patients and provide no information about how the disease will develop in prediabetic patients. Here, twenty-nine protein glycation sites were quantified after tryptic digestion of plasma samples at the peptide level using tandem mass spectrometry and isotope-labelled peptides as internal standard. The glycation degrees were determined in three groups, i.e., 48 patients with a duration of T2DM exceeding ten years, 48 non-diabetic individuals matched for gender, BMI, and age, and 20 prediabetic men. In long-term controlled diabetic patients, 27 glycated peptides were detected at significantly higher levels, providing moderate diagnostic accuracies (ACCs) from 61 to 79%, allowing a subgrouping of patients in three distinct clusters. Moreover, a feature set of one glycated peptides and six established clinical parameters provided an ACC of 95%. The same number of clusters was identified in prediabetic males (ACC of 95%) using a set of eight glycation sites (mostly from serum albumin). All patients present in one cluster showed progression of prediabetic state or advanced towards diabetes in the following five years. Overall, the studied glycation sites appear to be promising biomarkers for subgrouping prediabetic patients to estimate their risk for the development of T2DM. View Full-Text
Keywords: biomarker; fasting plasma glucose (FPG); glycated hemoglobin (HbA1c); glycation sites; multiple reaction monitoring (MRM); plasma proteins; type 2 diabetes mellitus (T2DM) biomarker; fasting plasma glucose (FPG); glycated hemoglobin (HbA1c); glycation sites; multiple reaction monitoring (MRM); plasma proteins; type 2 diabetes mellitus (T2DM)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Spiller, S.; Li, Y.; Blüher, M.; Welch, L.; Hoffmann, R. Diagnostic Accuracy of Protein Glycation Sites in Long-Term Controlled Patients with Type 2 Diabetes Mellitus and Their Prognostic Potential for Early Diagnosis. Pharmaceuticals 2018, 11, 38.

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