Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

Toma Keser, Ivan Gornik, Frano Vučković, Najda Selak, Tamara Pavić, Edita Lukić, Ivan Gudelj, Hrvoje Gašparović, Bojan Biočina, Therese Tilin, Annika Wennerström, Satu Männistö, Veikko Salomaa, Aki Havulinna, Wei Wang, James F. Wilson, Nishi Charutvedi, Markus Perola, Harry Campbell, Gordan LaucOlga Gornik

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesisBetter understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes.MethodsUsing a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 307 controls).ResultsIndividuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude.Conclusions/interpretationIncreased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications.KeywordsDiabetes predisposition Hyperglycaemia N-linked glycans Plasma N-glycome Type 2 diabetes
Original languageEnglish
JournalDiabetologia
Early online date13 Sep 2017
DOIs
Publication statusPublished - Dec 2017

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