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.

Highlights

  • Diabetes mellitus (DM) is a group of diseases characterized by hyperglycemia resulting from absolute insulin deficiency or insulin resistance, together with a relative insulin secretion defect

  • 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

  • Recent data indicate that every third adult living in developed countries has prediabetes [4,5], which is an intermediate state of hyperglycemia defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)

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Summary

Introduction

Diabetes mellitus (DM) is a group of diseases characterized by hyperglycemia resulting from absolute insulin deficiency (type 1 DM) or insulin resistance, together with a relative insulin secretion defect (type 2 DM). Recent data indicate that every third adult living in developed countries has prediabetes [4,5], which is an intermediate state of hyperglycemia defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). The latter is detected by an oral glucose tolerance test (OGTT). Prediabetes is connected to a high risk for developing diabetes and associated complications [8] indicating that early detection of prediabetic states followed by immediate lifestyle interventions including weight reduction, calorie-reduced diets and increased physical activity will allow preventing or slowing down the transition from prediabetes to T2DM [9]

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