Dataset Information

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

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, ?(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 ?(1,6)- and ?(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.

SUBMITTER: Testa R

PROVIDER: S-EPMC4368037 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

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

Testa Roberto R Vanhooren Valerie V Bonfigli Anna Rita AR Boemi Massimo M Olivieri Fabiola F Ceriello Antonio A Genovese Stefano S Spazzafumo Liana L Borelli Vincenzo V Bacalini Maria Giulia MG Salvioli Stefano S Garagnani Paolo P Dewaele Sylviane S Libert Claude C Franceschi Claudio C

PloS one 20150320 3

<h4>Background</h4>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 c ...[more]

PMID: 25793407

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Project description:BackgroundCardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increasingly diagnosed in older individuals who may have diabetes mellitus (DM). We evaluated the impact of DM on metabolic profile, renal and cardiovascular outcomes during treatment and follow-up of individuals with glomerulonephritis.MethodsWe performed a retrospective cohort study of 601 consecutive adults with biopsy-proven glomerulonephritis for factors associated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were excluded.ResultsThe median patient age was 49.8 years (36.7-60.9 years) with estimated glomerular filtration rate of 56.7 mL/min/1.73 m2 (27.7-93.2 mL/min/1.73 m2). DM was present in 25.4%. The most frequent diagnoses were minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) (29.5%), lupus nephritis (21.3%), immunoglobulin A (IgA) nephropathy (19.1%), and membranous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 individuals with lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, MCD/FSGS, membranous nephropathy, and IgA nephropathy, 52 (10.2%) developed kidney failure at a median 16.4 months (IQR, 2.3-32.2 months), while 29 (5.7%) had cardiovascular-related hospitalizations at 12.9 months (IQR, 4.8-31.8 months) and 31 (6.1%) died at 13.5 months (IQR, 2.5-42.9 months) after diagnosis. Cox regression analysis found that baseline DM was independently associated with kidney failure (adjusted hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.06-4.05, p = 0.03) and cardiovascular-related hospitalization (adjusted HR, 2.69; 95% CI, 1.21-5.98, p = 0.02) but not with mortality.ConclusionDM was strongly associated with kidney failure and hospitalization for cardiovascular events in patients with biopsy-proven glomerulonephritis.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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