High throughput profiling of whole plasma N-glycans in type II diabetes mellitus patients and healthy individuals: A perspective from a Ghanaian population

Eric Adua; Elham Memarian; Alyce Russell; Irena Trbojević-Akmačić; Ivan Gudelj; Julija Jurić; Peter Roberts; Gordan Lauc; Wei Wang

doi:10.1016/j.abb.2018.10.015

High throughput profiling of whole plasma N-glycans in type II diabetes mellitus patients and healthy individuals: A perspective from a Ghanaian population

Arch Biochem Biophys. 2019 Jan:661:10-21. doi: 10.1016/j.abb.2018.10.015. Epub 2018 Oct 24.

Authors

Eric Adua¹, Elham Memarian², Alyce Russell¹, Irena Trbojević-Akmačić², Ivan Gudelj², Julija Jurić², Peter Roberts¹, Gordan Lauc³, Wei Wang⁴

Affiliations

¹ School of Medical and Health Sciences, Edith Cowan University, 6027, WA, Australia.
² Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia.
³ Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia; University of Zagreb, Faculty of Pharmacy and Biochemistry, 10000, Zagreb, Croatia. Electronic address: glauc@genos.hr.
⁴ School of Medical and Health Sciences, Edith Cowan University, 6027, WA, Australia; School of Public Health, Taishan Medical University, Taian, 271000, Shandong, China; Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, 100069, China. Electronic address: wei.wang@ecu.edu.au.

PMID: 30365935
DOI: 10.1016/j.abb.2018.10.015

Abstract

Aberrant protein glycosylation may reflect changes in cell metabolism of type II diabetes mellitus (T2DM) and offers fresh vistas for discovering potential biomarkers. However, the functional significance of T2DM N-glycan alterations is underexplored, since to date, N-glycan profiling studies have been performed in selected populations. Geographically and genetically isolated populations are needed for validation of specific biomarkers. This age-sex matched cross sectional study comprising 232 T2DM patients and 219 controls was conducted in Ghana, Western Africa. Blood plasma samples were collected for clinical assessment after which plasma N-glycans were freed and analysed by ultra-performance liquid chromatography (UPLC). High branching (HB) [W = 46328; q = 0.00072], tri-galactosylated (G3) [W = 44076; q = 0.00096], antennary fucosylated (FUC_A) [W = 43055; q = 0.0000763], and triantennary (TRIA) [W = 44624; q = 0.0025], N-glycan structures were increased in T2DM whereas low branching (LB) [W = 46328; q = 0.00072], non-sialylated (S0) [W = 46929; q = 0.00292], monogalactosylation (G1) [W = 44091; q = 0.0000763], core fucosylation (FUC_C), [W = 46497; q = 0.00096], biantennary galactosylation (A2G) [W = 45663; q = 0.000763], and biantennary (BA) [W = 46376; q = 0.00072], structures were decreased compared to controls. Nine N-glycan peaks (GPs (GP1, GP4, GP7, GP11, GP17, GP19, GP22, GP26, GP29)) were found to predict case status based on Akaike's information criterion (AIC) and Bayesian information criterion (BIC) model selection. Adjusting for age, sex and other co-variates in this model yielded an area under the curve (AUC) of 80.5% with sensitivity of 79% and specificity of 73%, indicating the predicting power of N-glycans as robust biomarkers. Our results show that hyperglycemia influences N-glycan complexities among Ghanaians. N-glycan profiling in distinct populations has affirmed the potentiality of N-glycan profiles as generic biomarkers which may facilitate better prognosis for T2DM.

Keywords: Biomarker; N-Glycans; Type II diabetes mellitus; Ultra-performance liquid chromatography.

Publication types

Clinical Trial
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers / blood
Cross-Sectional Studies
Diabetes Mellitus, Type 2 / blood*
Female
Ghana
Humans
Male
Middle Aged
Polysaccharides / blood*

Substances

Biomarkers
Polysaccharides