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Background  Early diagnosis of type 2 diabetes mellitus (T2DM) is still difficult. Screening of plasma biomarkers has great significance of optimizing diagnosis and predicting the complications of T2DM.    Methods  We used a special diet, Purina #5008, to induce diabetes in Zucker leptin receptor gene-deficient rats (fa/fa) to establish Zucker diabetic fatty (ZDF) rats, simulating the early stage of T2DM. The differentially expressed proteins (DEP) and lipids (DEL), as potential biomarkers, were screened to compare the plasma expression levels in ZDF rats and their basic diet-fed wild-type controls (fa/+) by Tandem Mass Tags (TMT) and liquid chromatography-tandem mass spectrometry.    Results  These two groups had different plasma proteins and lipids profiles consisting of 84 DEPs and, 179 DELs identified in the positive ion mode and 178 DELs in the negative ion mode, respectively. Enrichment analysis of these different indicators showed that oxidative stress, insulin resistance and metabolic disorders of glycan and lipid played an important role in generating the difference. Some markers can be used as candidate biomarkers in prediction and treatments of T2DM, such as ceruloplasmin, apolipoprotein C-I, apolipoprotein C-II and apolipoprotein C-IV.    Conclusion  These plasma differences help to optimize the diagnosis and predict the complications of T2DM, although this remains to be verified in the crowd. Trace elements related-metalloproteins, such as ceruloplasmin, and lipid metabolism and transport-related apolipoprotein C are expected to be candidate biomarkers of T2DM and should be given more attention.

Metalloproteins and apolipoprotein C: candidate plasma biomarkers of T2DM screened by comparative proteomics and lipidomics in ZDF rats