title: O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males.
abstract: BACKGROUND
  Hemoglobin 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Results 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.
authors.affiliation: Faculty of Kinesiology, University of Calgary, 3300 University Drive NW, Calgary, Alberta T2N 4N1 Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Myslicki
authors.affiliation: Faculty of Kinesiology, University of Calgary, 3300 University Drive NW, Calgary, Alberta T2N 4N1 Canada ; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4 Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.affiliation: Faculty of Kinesiology, University of Calgary, 3300 University Drive NW, Calgary, Alberta T2N 4N1 Canada.
authors.forename: Dustin S
authors.initials: DS
authors.lastname: Hittel
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4 Canada.
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Hughey
authors.affiliation: Faculty of Kinesiology, University of Calgary, 3300 University Drive NW, Calgary, Alberta T2N 4N1 Canada.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Belke
keywords: HOMA-IR; Insulin resistance; Metabolism; Obesity; Young adult