In conditions of hyper-homocysteinaemia (HHcy), such as in diabetes, vascular disease or certain inflammatory disorders, Hcy-driven MMP-9 activity promotes a feed-forward loop: ECM disruption strengthens inflammatory cell activity, inflammation sustains Hcy-mediated cell stress and MMP-9 induction, and barrier damage accelerates organ dysfunction. This evidence concerns the gene MMP9 and diabetes mellitus.