Methylglyoxal, a Diabetic Biomarker for Insulin Resistance, Vascular Dysfunction and Neuropathies

Diabetes mellitus is a pandemic metabolic disease characterized by chronically elevated blood glucose concentration due to insulin dysfunction. Diabetics are prone to limbs fungal infections and ulcers due to vascular injury and end-organ damage such as nephropathy, retinopathy and neuropathic pain all of which are associated with methylglyoxal elevation. Methylglyoxal is generated through carbohydrate, lipid and protein metabolism which are all found to be exacerbated in diabetes. Moreover, methylglyoxal is highly reactive with various cellular and interstitial molecules such as proteins and phospholipids to form stable adducts and advanced glycation end products. Methylglyoxal induces insulin resistance, pancreatic β-cells cytotoxicity, and induces endothelial dysfunction that accelerates retinopathy, another diabetes complication. Additionally, methylglyoxal induces hyperalgesia and neuronal inflammation associated with neuropathic pain. Therefore, methylglyoxal might represent a potential therapeutic target in diabetes and associated complications.