The potential of N-glycosylation profiles as biomarkers for monitoring the progression of Type II diabetes mellitus towards diabetic kidney disease

Background: On a global scale, type II diabetes mellitus (T2DM) remain a major health problem and it is the driver for chronic kidney disease (CKD). Despite this association, we still do not have sufficient biomarkers to anticipate better outcomes. N-glycosylation profiles are robust biomarkers and can be used for early monitoring of the progression of T2DM towards CKD. Methods: In this cross-sectional study, we recruited 241 T2DM patients from January to May 2016. Demographic and anthropometric data were collected, following which fasting blood samples were collected for clinical analyses. Renal function decline was determined by estimation of glomerular filtration rate (eGFR) and N-glycosylation profiles were analysed by Ultra-performance liquid chromatography (UPLC). Results: The prevalence of undiagnosed CKD was 31.53%. Compared to men, women had a statistically significantly higher HbA1c (p = 0.031), TG (p = 0.015), HDL-c (p < 0.0001), creatinine (<0.0001), urea (p < 0.028) and uric acid (p < 0.0001). T2DM patients with undiagnosed CKD had higher serum creatinine (145.75 ± 50.83 vs 88.59 ± 19.46, p < 0.0001), higher uric acid (361.10 ± 115.37 vs 294.54 ± 97.75; p < 0.0001) and higher urea (5.17 ± 2.35 vs 3.58 ± 1.19; p < 0.0001). After performing logistic regression and adjusting for age, sex and BMI, three N-glycan peaks [OR (95%CI): (GP12 (0.05(0.01–0.54), p = 0.013)); GP16 (0.61(0.43–0.87), p = 0.006)); GP22 (0.60(0.39–0.92), p = 0.018)) were associated with renal function. Conclusion: There was an increased prevalence of undiagnosed CKD among T2DM patients. This prevalence is the consequence of uncontrolled modifiable risk factors, which collectively may lead to end stage renal disease (ESRD). Although, the identified N-glycans could not adequately predict incident CKD, our investigation indicates the potential role of N-glycosylation in renal function and that their inclusion may improve risk stratification for CKD.