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J Clin Endocrinol Metab. 2012 Dec;97(12):4640-9. doi: 10.1210/jc.2012-2229. Epub 2012 Oct 12.

Exploring leukocyte O-GlcNAcylation as a novel diagnostic tool for the earlier detection of type 2 diabetes mellitus.

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  • 1Cardio-Metabolic Research Group, Department of Physiological Sciences, Stellenbosch University, Room 2005, Mike De Vries Building, Merriman Avenue, Stellenbosch 7600, South Africa.

Abstract

CONTEXT:

Because current tests available for the diagnosis of diabetes have shortcomings, a novel screening method for the earlier and more efficient detection of type 2 diabetes would be a significant clinical advance.

OBJECTIVE:

The hexosamine biosynthetic pathway usually acts as a fuel sensor, and its activation leads to O-linked β-N-acetylglucosamine (O-GlcNAc) modification of target proteins (O-GlcNAcylation) in a glucose-responsive manner. O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are responsible for O-GlcNAc addition and removal, respectively. Because higher hexosamine biosynthetic pathway flux is linked to insulin resistance/type 2 diabetes, we hypothesized that increased O-GlcNAcylation of leukocyte proteins can detect the onset of pre- and overt diabetes.

DESIGN, SETTING AND PATIENTS:

Seventy-four participants from Bellville and Stellenbosch (Western Cape, South Africa) were recruited and classified as normal, prediabetic, and diabetic individuals (American Diabetes Association criteria).

MAIN OUTCOME MEASURES:

Leukocytes isolated from study subjects were evaluated for O-GlcNAc, OGA, and O-GlcNAc transferase expression by flow cytometry and immunofluorescence microscopy.

RESULTS:

Flow cytometric analysis of leukocyte subtypes revealed increased O-GlcNAcylation in granulocytes vs. lymphocytes (P < 0.001). Diabetic individuals displayed higher leukocyte O-GlcNAcylation (P < 0.01), whereas granulocyte analysis showed an increase for prediabetic subjects (P < 0.01). However, OGA expression increased in leukocytes of diabetic subjects and is likely an adaptation to attenuate higher O-GlcNAcylation observed (P < 0.001).

CONCLUSIONS:

Together our data demonstrate that leukocyte (particularly granulocyte) O-GlcNAcylation could help detect pre- and overt diabetes and offer clinical value as unique markers for the earlier and more efficient detection of type 2 diabetes.

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PMID:
23066116
[PubMed - indexed for MEDLINE]
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