Diabetes mellitus (DM) affects 537 million adults (10% of the population) worldwide.1 DM is characterized by elevated blood glucose (hyperglycemia); the pancreas produces insufficient insulin, but may also be associated with insulin resistance.2

Hyperglycemia affects the endothelial glycocalyx (eGCX) and leads to complications affecting the eyes, kidneys, nervous and cardiovascular system.3 Cardiomyopathy, atherosclerosis, and heart failure are the major macrovascular complications; diabetic nephropathy, retinopathy and neuropathy are microvascular complications. The syndecans (SDCs) are the major proteoglycans in the eGCX. The SDCs convert into soluble active ligands that can modulate biological processes through a process called shedding. Hyperglycemia increases SDCs shedding.4 SDCs shedding is involved in the development of diabetic complications. Recent studies suggest that DM can alter the structure and function of SDC which can then lead to the pathology associated with DM. Understanding the diabetic changes to SDCs may provide new opportunities to treat the complications of DM. In this review, we discuss previous studies that have used animal models and human-based approaches to better understand the role of SDCs in the onset and progression of diabetic complications.