title: 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, 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.
authors: Experimental models in Clinical Pathology, Italian National Research Center on Aging (INRCA), Ancona, 60127, Italy.
authors: Roberto
authors: R
authors: Testa
authors: VIB Inflammation Research Center, Technologiepark 927, B-9052, Ghent, Belgium; Department of Molecular Biology, Ghent University, Technologiepark 927, B-9052, Ghent, Belgium.
authors: Valerie
authors: V
authors: Vanhooren
authors: Scientific Direction, Italian National Research Center on Aging (INRCA), Ancona, 60124, Italy.
authors: Anna Rita
authors: AR
authors: Bonfigli
authors: Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), 60127, Ancona, Italy.
authors: Massimo
authors: M
authors: Boemi
authors: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, 60020, Italy; Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA), Ancona, 60127, Italy.
authors: Fabiola
authors: F
authors: Olivieri
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, 08017, Spain.
authors: Antonio
authors: A
authors: Ceriello
authors: Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni (MI), 20099, Italy.
authors: Stefano
authors: S
authors: Genovese
authors: Center of Biostatistic, Italian National Research Center on Aging (INRCA), Ancona, 60124, Italy.
authors: Liana
authors: L
authors: Spazzafumo
authors: Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, 40126, Italy.
authors: Vincenzo
authors: V
authors: Borelli
authors: Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, 40126, Italy.
authors: Maria Giulia
authors: MG
authors: Bacalini
authors: Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, 40126, Italy.
authors: Stefano
authors: S
authors: Salvioli
authors: Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, 40126, Italy; Center for Applied Biomedical Research, St. Orsola-Malpighi University Hospital, Bologna, 40138, Italy; Interdepartmental Centre "L. Galvani" CIG, University of Bologna, Piazza di Porta S. Donato 1, Bologna, 40126, Italy.
authors: Paolo
authors: P
authors: Garagnani
authors: VIB Inflammation Research Center, Technologiepark 927, B-9052, Ghent, Belgium; Department of Molecular Biology, Ghent University, Technologiepark 927, B-9052, Ghent, Belgium.
authors: Sylviane
authors: S
authors: Dewaele
authors: VIB Inflammation Research Center, Technologiepark 927, B-9052, Ghent, Belgium; Department of Molecular Biology, Ghent University, Technologiepark 927, B-9052, Ghent, Belgium.
authors: Claude
authors: C
authors: Libert
authors: Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, 40126, Italy; Center for Applied Biomedical Research, St. Orsola-Malpighi University Hospital, Bologna, 40138, Italy; Interdepartmental Centre "L. Galvani" CIG, University of Bologna, Piazza di Porta S. Donato 1, Bologna, 40126, Italy; IRCCS, Institute of Neurological Sciences of Bologna, Bologna, 40124, Italy.
authors: Claudio
authors: C
authors: Franceschi
mesh_terms: D000368:Aged; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D005260:Female; D054794:Glycomics / Q000379:methods; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism*; D008875:Middle Aged; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; D011134:Polysaccharides