Dietary glycocalyx mimetic reduces vascular risk in Type 2 diabetes: evidence from urinary peptidomic classifiers in a South-Asian Surinamese Cohort

Abstract

Aims: Following up on a prior placebo-controlled trial (NCT03889236), we examined the effects of an oral glycocalyx-mimetic supplement and a fasting-mimicking diet (FMD) on three urinary peptidomic-based classifiers, which indicate future heart failure (HF2), coronary artery disease (CAD160), and chronic kidney disease (CKD273) risk in South-Asian Surinamese adults with type 2 diabetes mellitus. Methods: Forty-four participants were randomly allocated to one of three 12-week interventions: daily glycocalyx-mimetic capsules (n = 18), placebo (n = 14), or a five-day FMD repeated every four weeks (n = 12). Baseline and week-12 urine were profiled via capillary electrophoresis-mass spectrometry (CE-MS). The pre-validated support vector machine (SVM) classifiers (HF2, CAD160, CKD273) produced risk scores that were evaluated through paired t-tests for each group. Peptide-level changes were analyzed using paired Wilcoxon signed-rank tests, and all p-values were Benjamini-Hochberg corrected (alpha = 0.05). Results: Glycocalyx-mimetic supplementation significantly reduced HF2 scores (mean Delta=-0.58, 95 % CI-0.83 to-0.33, adjusted p < 0.001) and altered the abundance of 17 peptides, primarily decreasing collagen-derived fragments, suggesting improved extracellular-matrix turnover. The risk scores for CAD160 and CKD273 remained unchanged. FMD and placebo did not produce any meaningful changes in classifier scores. Conclusions: In this cohort, glycocalyx-mimetic supplementation improved the urinary peptidomic signature associated with heart-failure risk, whereas an FMD did not. Urinary peptidomics offers a sensitive molecular method for monitoring the effects of (dietary) interventions.