Diabetes Metab J.  2021 May;45(3):349-357. 10.4093/dmj.2019.0211.

Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy

• Choi MS
• Jun JE
• Park SW
• Yoo JH
• Ahn J
• Kim G
• Jin SM
• Hur KY
• Lee MK
• Kim JH

• KMID: 2516337
• DOI: http://doi.org/10.4093/dmj.2019.0211

Abstract

Background
Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy.
Methods
This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed.
Results
The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV.
Conclusion
This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

Keyword

Diabetes mellitus, type 1; Diabetic nephropathies; Diabetic neuropathies

Figure

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  Fig. 1. Flowchart for selection of study subjects. uNAG, urinary N-acetyl-β-D-glucosaminidase; uACR, urine albumin-to-creatinine ratio; GFR, glomerular filtration rate.

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  Fig. 2. Scatter plots of Pearson’s correlation coefficients between parameters of heart rate variability and urinary N-acetyl-β-Dglucosaminidase (uNAG) in subjects with type 1 diabetes mellitus without albuminuria. (A) Correlation between log-low frequency (LF) and log-uNAG (Pearson’s correlation R2=0.0882, P<0.001). (B) Correlation between log-high frequency (HF) and log-uNAG (Pearson’s correlation R2=0.0802, P<0.001). (C) Correlation between log-standard deviation of all NN intervals (SDNN) and log-uNAG (Pearson’s correlation R2=0.0757, P<0.001). (D) Correlation between log-root mean square of successive RR interval differences (RMSSD) and log-uNAG (Pearson’s correlation R2=0.0659, P<0.001).

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