Diabetes & Metabolism Journal

Original Article

Complications
Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus: Hae Kyung Kim, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee; Diabetes Metab J. 2022;46(1):104-116. Published online July 13, 2021; DOI: https://doi.org/10.4093/dmj.2020.0273

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Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

Citations

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Review

O-GlcNAc Modification: Friend or Foe in Diabetic Cardiovascular Disease: Udayakumar Karunakaran, Nam Ho Jeoung; Korean Diabetes J. 2010;34(4):211-219. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.211

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Abstract PDF PubReader

O-Linked β-N-acetyl glucosaminylation (O-GlcNAcylation) is a dynamic post-translational modification that occurs on serine and threonine residues of cytosolic and nuclear proteins in all cell types, including those involved in the cardiovascular system. O-GlcNAcylation is thought to act in a manner analogous to protein phosphorylation. O-GlcNAcylation rapidly cycles on/off proteins in a time scale similar to that for phosphorylation/dephosphorylation of proteins. Several studies indicate that O-GlcNAc might induce nuclear localization of some transcription factors and may affect their DNA binding activities. However, at the cellular level, it has been shown that O-GlcNAc levels increase in response to stress and augmentation of this response suppresses cell survival. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are major hallmarks of type 2 diabetes and diabetes-related cardiovascular complications. Thus, O-GlcNAc and its metabolic functions are not yet well-understood; focusing on the role of O-GlcNAc in the cardiovascular system is a viable target for biomedical investigation. In this review, we summarize our current understanding of the role of O-GlcNAc on the regulation of cell function and survival in the cardiovascular system.

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Journal of Biological Chemistry.2012; 287(35): 30024. CrossRef
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Diabetes.2011; 60(5): 1399. CrossRef

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