Type II diabetes mellitus (T2DM) is a well-recognised cause of death worldwide. In fact, over one million deaths in 2015 were attributed to T2DM while the disease prevalence is still rising. This is because, despite considerable efforts, we still do not have reliable diagnostic and prognostic biomarkers to anticipate effective treatments, support better clinical outcomes, and move towards personalised medicine. Recently, N-glycosylation profiles have emerged as robust and field tested candidates for improving patient stratification and revolutionising T2DM therapeutics. Glycans bind to protein backbone in a process termed glycosylation and thus far, it is regarded as the most complex and abundant co- and post-translational process in the cell. N-glycans which are a subclass of glycan types bind to asparagine side chains of proteins in the consensus sequence Asn-X-Thr/Ser (where X is any amino acid except proline).
Although these structures are fairly stable within an individual they change under influence of an external perturbation, with different physiological parameters such as age, and pathophysiological conditions such as metabolic syndrome and T2DM.
In this study, we undertook an observational study to determine plasma N-glycosylation patterns longitudinally among 253 T2DM patients and the correlations between environmental factors and derived plasma N-glycan traits over a 6-month period.
From January to April 2016, 253 Ghanaian T2DM individuals were recruited (in Ghana, Western Africa) and depending on the date of first visit, each participant was called back after 6 months.
Demographic and anthropometric information were obtained while fasting blood samples were collected for clinical assessments. After which plasma N-glycans were freed, fluorescently labelled and analyzed by ultra-performance liquid chromatography (UPLC).
Followed by Wisconsin’s Ranked Sum (paired) tests and Spearman correlations for data analyses. Two tailed q-value <0.05 after adjusting for false discovery rate was considered significant.
There were statistical differences between males and females at baseline: body mass index (BMI) (χ2=13.26, q=0.0080), education (χ2=20.3, q=0.0003), occupation (χ2=23.08, q=0.0003), waist to height ratio (U=4733.5, q=0.0001), triglycerides (U=5919, q=0.0458) and high density lipoproteins (HDL-c) (U=4485, q=0.0001). Significant differences were observed between baseline and follow up: HDL-c (W=526, q=0.000), low density lipoprotein cholesterol (LDL-c) (W=6488, q=0.002) and TG (W=2513, q=0.000). However, fasting plasma glucose (FPG) and total cholesterol (TC) were not statistically different at baseline and follow up. Similarly, plasma N-glycosylation profiles were unchanged when comparing paired data at baseline and follow up.
Our results showed moderate differences in biochemical measures at baseline compared to follow up. However, these did not cause a significant change in plasma N-glycosylation profiles. The study makes a significant contribution to our understanding of the stability or constancy of plasma N-glycosylation profiles in the absence of co-morbidities.
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