The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.