Abstract
BackgroundHemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. However, it has proven to be insensitive at pre-diabetic threshold values. O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. Healthy, young males (18–35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts.FindingsThe relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. Moreover, a positive association between HOMA-IR and O-GlcNAc emerged, while no relationship was found between HbA1c and HOMA-IR. This effect was not related to OGT expression.ConclusionsResults indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies.Electronic supplementary materialThe online version of this article (doi:10.1186/1758-5996-6-96) contains supplementary material, which is available to authorized users.
Highlights
Current estimates indicate there are 347 million diagnosed cases of diabetes worldwide, 90% of these being attributable to type 2 diabetes (T2D) [1]
Results indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to Hemoglobin A1c (HbA1c) in this population
The extent of metabolic disease risk in children and young adults is correlated with the presence of the same risk factors identified in adults including obesity and insulin resistance [2]
Summary
Current estimates indicate there are 347 million diagnosed cases of diabetes worldwide, 90% of these being attributable to type 2 diabetes (T2D) [1]. Studies have examined changes in the O-GlcNAc of erythrocytes and leukocytes of healthy, pre-diabetic and overtly diabetic adults in order to gain an enhanced understanding of this modification as it relates to the development of the disease [4,7,8]. These studies show that in overt diabetes, O-GlcNAc analysis has the potential to identify metabolic disturbances better than HbA1c [7,8]. Young males (18–35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts
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