Intrinsic factors implicated in the sequence of diabetic ulceration : the potential role of core2 B1,6-N-acetylglucoseaminyltransferase (core2GlcNAcT-I) (core 2 transferase)

Abstract

Peripheral neuropathy is an insidious complication of diabetes mellitus with notable secondary events, such as vascular dysfunction and plantar ulceration. Traditional doctrine maintains that diabetic ulceration is a direct consequence of concurrent neuropathy and pressure. It was hypothesised that neuropathic ulceration is promoted by capillary occlusion, the resultant hypoxia leading to expeditious cell death. The Golgi enzyme, core 2 transferase, was implicated in this event, given its mediation of intercellular signalling and leukocyte / endothelial adhesion. Hence, an upregulation of this particular facilitator would increase leukocyte / endothelial binding and thereby, effect microcirculatory stasis and post-occlusion ischaemia.

Type II diabetic study groups, with and without neuropathy (n=20), were canvassed and set against aged matched non-diabetic controls (n=5). All participants were subjected to anthropometric testing prior to venous blood sampling for the key marker, core 2 transferase. Additional blood chemistry and clinical testing (VPT and 10g monofilament) was further undertaken to demonstrate possible correlations with core 2 transferase upregulation.

The outcome of this study identified that core 2 transferase was significantly elevated in both diabetic study groups, in comparison to control participants (p<0.001). This trend was further continued, when comparing diabetic neuropathic individuals to both remaining groups (p<0.001). Subsequent linear regression modelling identified three principal correlations with core 2 transferase over-expression: VPT, 10g monofilament and creatinine levels. Using each of the above correlations as independent co-variates, adjusted models identified a very robust Rsq of 0.911 (91% predictability) for VPT and creatinine, as clinical markers for core 2 transferase specificity.

Consequently, these findings positively implicate core 2 transferase activity within a diabetic population and moreover, offer validated clinical tools to facilitate its early detection.

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