Dataset Information

A new strategy for early diagnosis of type 2 diabetes by standard-free, label-free LC-MS/MS quantification of glycated peptides.

ABSTRACT: The early diagnosis of diabetes, one of the top three chronic incurable diseases, is becoming increasingly important. Here, we investigated the applicability of an (18)O-labeling technique for the development of a standard-free, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the early diagnosis of type 2 diabetes mellitus (T2DM). Rather than attempting to identify quantitative differences in proteins as biomarkers, glycation of the highest abundance protein in human plasma, human serum albumin (HSA), was monitored through quantitative analysis of HSA characteristic peptides using the (18)O-labeling technique. Eight glucose-sensitive peptides and one glucose-insensitive peptide were discovered. The glucose-insensitive peptide served as the internal standard, and a standard-free, label-free LC-MS/MS method was developed. This method was then used to select putative biomarkers for T2DM in a clinical trial with 389 human plasma samples. As a result, three of the eight glucose-sensitive peptides (FKDLGEENFK, LDELRDEGK, and KVPQVSTPTLVEVSR) were selected and could be used as potential biomarkers for the early diagnosis of T2DM.

SUBMITTER: Zhang M

PROVIDER: S-EPMC3806625 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A new strategy for early diagnosis of type 2 diabetes by standard-free, label-free LC-MS/MS quantification of glycated peptides.

Zhang Mei M Xu Wei W Deng Yulin Y

Diabetes 20130726 11

The early diagnosis of diabetes, one of the top three chronic incurable diseases, is becoming increasingly important. Here, we investigated the applicability of an (18)O-labeling technique for the development of a standard-free, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the early diagnosis of type 2 diabetes mellitus (T2DM). Rather than attempting to identify quantitative differences in proteins as biomarkers, glycation of the highest abundance protein in hu ...[more]

PMID: 23894188

Similar Datasets

Project description:N-1-(deoxyfructosyl) valine of β-hemoglobin, commonly referred to as HbA1c, is the "gold standard" for clinical detection of diabetes. Instead of quantifying the full-length HbA1c glycated protein, in the present study, we proposed the peptide-based strategy to quantify the depletion of the tryptic peptides of hemoglobin for the diagnosis of type 2 diabetes mellitus (T2DM). The peptides were discovered and validated as T2DM biomarkers by label-free LC-ESI-DMRM method without reference material. The glucose could react with hemoglobin's free amino group of N-terminus and ϵ-amino group of lysine residues and leave the modification on the hemoglobin tryptic peptides. Thus, there are two types of peptides in the hemoglobin: sensitive peptides and insensitive peptides to glucose due to the differential sensitivity of lysine residues to glycation. To discover two types of peptides of hemoglobin, we first developed the assay of liquid chromatography-electrospray ionization mass spectrometry coupled with dynamic multiple reaction monitoring. The protein coverage reaches 94.2%. Moreover, the hemoglobin was incubated with the 500 mmol/L glucose for 20 days, 40 days and 60 days in vitro to screen the sensitive peptides and insensitive peptides to glucose. A total of 14 sensitive peptides and 4 insensitive peptides were discovered. Furthermore, the LC-ESI-DMRM method was also utilized to validated the glucose-sensitive peptides by 40 clinical samples with healthy control individuals (n = 20) and type 2 diabetes mellitus patients (n = 20). Three putative sensitive peptides (LLGNVLVCVLAHHFGK, VVAGVANALAHKYH, LRVDPVNFK) from the hemoglobin showed excellent sensitivity and specificity based on receiver operating characteristic analysis and were verified as the promising biomarkers for the diagnosis of diabetes mellitus. And one peptide (LLVVYPWTQR) was found as glucose-insensitive peptide. Taken together, the findings of this study suggest that quantification of hemoglobin tryptic peptides using label-free and standard-free LC-ESI-DMRM is an alternative method for the diagnosis of T2DM, which could be combined with other MS-based blood biomarkers for diagnosis of multiple diseases in MS single shot.

Dataset Information

A new strategy for early diagnosis of type 2 diabetes by standard-free, label-free LC-MS/MS quantification of glycated peptides.

Publications

A new strategy for early diagnosis of type 2 diabetes by standard-free, label-free LC-MS/MS quantification of glycated peptides.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets