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. 2015 Mar 20;10(3):e0119983.
doi: 10.1371/journal.pone.0119983. eCollection 2015.

N-glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters

Roberto Testa  1 , Valerie Vanhooren  2 , Anna Rita Bonfigli  3 , Massimo Boemi  4 , Fabiola Olivieri  5 , Antonio Ceriello  6 , Stefano Genovese  7 , Liana Spazzafumo  8 , Vincenzo Borelli  9 , Maria Giulia Bacalini  9 , Stefano Salvioli  9 , Paolo Garagnani  10 , Sylviane Dewaele  2 , Claude Libert  2 , Claudio Franceschi  11
Affiliations

N-glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters

Roberto Testa et al. PLoS One. .

Abstract

Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome.

Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins.

Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS).

Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. 1A. The abundance of α(1,6)-arm monogalactosylated, core-α-1,6-fucosylated diantennary glycan NG1(6)A2F, assessed by peak 3 (P3) levels, in CTR and T2DM patients with and without MS.
The boxplots represent a comparison of peak 3 levels in males in six classes of subjects: CTR without MS, CTR with MS, T2DM- without MS, T2DM- with MS, T2DM+ without MS, T2DM+ with MS. 1B. The abundance of α(1,6)-arm monogalactosylated, core-α-1,6-fucosylated diantennary glycan NG1(6)A2F, assessed by peak 3 (P3) levels, in CTR and T2DM patients with and without MS. The boxplots represent a comparison of peak 3 levels in females in six classes of subjects: CTR without MS, CTR with MS, T2DM- without MS, T2DM- with MS, T2DM+ without MS, T2DM+ with MS.
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