Urinary N-acetyl-β-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes

Abstract

Recently, several renal tubular damage markers have gained considerable attention because of their clinical implications as sensitive and specific biomarkers for early stage diabetic kidney disease. However, little is known about the demographic and glucometabolic factors affecting levels of urinary N-acetyl-β-d-glucosaminidase (NAG), a marker of proximal tubular damage, in type 2 diabetes mellitus (T2DM).The aim of this study was to investigate the clinical relevance of urinary NAG with regard to demographic and glucometabolic parameters, as well as nephropathic parameters, by comparing the glomerulopathic marker of albuminuria.In this retrospective cross-sectional study, we enrolled a total of 592 patients with either prediabetes (N = 29) or T2DM (N = 563). Glucometabolic parameters (glucose, hemoglobin A1c, glycated albumin [GA], insulin, C-peptide, homeostasis model assessment [HOMA] of insulin resistance, HOMA-β, postprandial C-peptide-to-glucose ratio [PCGR], and urinary glucose-to-creatinine ratio) and nephropathic parameters (urinary NAG, albumin-to-creatinine ratio [ACR], and estimated glomerular filtration rate) were measured.The levels of urinary NAG showed moderate positive correlation with the levels of urinary ACR in T2DM (r = 0.46). In correlation analysis, urinary NAG was more strongly correlated with body mass index (BMI) (r = −0.22; P < 0.001 vs. r = −0.02; P = 0.74), plasma stimulated glucose (r = 0.25; P < 0.001 vs. r = 0.08; P = 0.10), GA (r = 0.20; P < 0.001 vs. r = 0.13; P = 0.01), PCGR (r = −0.17; P = 0.001 vs. r = −0.09; P = 0.11), and HOMA-β (r = −0.10; P = 0.05 vs. r = −0.02; P = 0.79) than urinary ACR. In multiple regression analysis, age, lower BMI, stimulated glucose, GA, and urinary ACR predicted increased urinary NAG.In conclusion, increase in urinary NAG may be related to glycemic parameters reflecting glucose fluctuation and decreased insulin secretory capacity in patients with T2DM. Further longitudinal, prospective studies are needed to investigate a causal relationship between glucose fluctuations, renal tubular damage, and other vascular complications of diabetes.

Correlation of Urine N-Acetyl-Beta-D-Glucosaminidase Activity With Urine Albumin Creatinine Ratio in Type 2 Diabetes Mellitus

“…Similarly, a research conducted by Bouvet et al 10 also revealed a strong and statistically significant correlation between urine NAG and UACR (r=0.628) (p<0.001) in type 2 DM patients. Unlike the research conducted by Bouvet et al, a research conducted by Kim et al 11 showed a moderate and statistically significant correlation between urine NAG and UACR (R=0.458) (p<0.001) in patients with type 2 DM.…”

“…16 Nevertheless, this research did not measure BMI of each research subject. Thus, the different median values of UACR in this research from those in the previous researches conducted by Piwowar et al 12 and Kim et al 11 may be related to differences in GFR and BMI of the research subjects.…”

“…Unlike these results, a research conducted by Piwowar et al 12 showed that the median value of UACR was 109 (259) mg/g in type 2 DM patients. A research conducted by Kim et al 11 even also revealed that the median value of UACR was 17.43 (52.92) mg/g in patients with type 2 diabetes.…”

“…In addition, a research conducted by Bouvet et al 10 on the clinical use of NAG in Argentina showed that there was a stronger correlation of NAG (r=0.628; p <0.0001) with UACR than with levels of blood glucose, HbA1c, serum creatinine and glomerular filtration rate. Meanwhile, a research conducted by Kim et al 11 on the usefulness of NAG in patients with type 2 diabetes in South Korea argued that there was a moderate correlation of NAG with UACR (r=0.458, p<0.001). As a result, this research aimed to reveal the correlation of NAG with UACR in type 2 diabetes patients visiting the Dr. M. Djamil Hospital in Padang.…”

Association Between Clinical Biomarkers and Optical Coherence Tomography Angiography Parameters in Type 2 Diabetes Mellitus

“…18,19 The role of insulin indices as DR biomarker is of increasing interest. 20 We expected that subclinical microvascular abnormalities of the macula appearing on OCT-A assessments might serve as a noninvasive and useful biomarker showing a significant correlation with some of the most representative and common existing biomarkers of DR.…”