Urinary N-Acetyl-β-d-Glucosaminidase (NAG) Levels and Risk of Cardiovascular Events in Diabetic Patients

Figures & data

Table 1 Clinical Characteristics in Patients with Type 2 Diabetes Mellitus (N = 357)

Characteristic	eGFR ≥ 60 mL/Min per 1.73 m^2 (N = 178)	eGFR < 60 mL/Min per 1.73 m^2 (N = 179)	P value
Age (Y)	68.3±9.6	70.5±10.6	0.009
Male, n (%)	105 (58.9)	102 (57.0)	0.158
CV events, n (%)	8 (4.5)	18 (10.1)	<0.001
Duration of diabetes (years)	6.9 (4.1–12.4)	11.9 (7.3–13.3)	<0.001
Smoking history, n (%)	64 (36.0)	71 (39.7)	0.045
Drinker history, n (%)	102 (57.3)	111 (62.0)	0.052
BMI (kg/m^2)	27.3±6.3	29.5 ±7.1	<0.001
Systolic blood pressure (mmHg)	146.4±11.8	155.5±16.4	<0.001
Diastolic blood pressure (mmHg)	83.1±9.3	87.5±9.8	<0.001
Moderate physical activity, n (%)	66 (37.1)	72 (40.2)	0.096
Urinary NAG (IU/L)	32.6±4.2	41±4.8	<0.001
Urinary NAG (U/g creatinine)	4.3 (2.1–7.2)	12.6 (8.4–17.2)	<0.001
Estimated GFR (mL/min per 1.73 m2)	70.6±5.7	48.4±6.9	<0.001
Serum albumin (g/L)	43.4±3.1	38.3±3.6	<0.001
Serum hemoglobin (g/L)	115±19	108±19	0.079
Serum C-reactive protein (mg/L)	1.9 (0.6–7.6)	7.3 (1.1–12.5)	<0.001
Serum total cholesterol (mmol/L)	5.1±0.2	5.4.±0.3	0.134
Serum triglycerides (mmol/L)	3.4±0.2	3.5±0.4	0.115
Serum HDL cholesterol (mmol/L)	1.4±0.1	1.6±0.2	<0.097
Serum LDL cholesterol (mmol/L)	1.6±0.4	1.7±0.5	0.231
Serum creatinine (mmol/L)	68 ±5	135 ±11	<0.001
Serum uric acid (mmol/L)	288 ±10	305 ±13	0.042
Hemoglobin A1c (%)	6.8±0.3	6.9±0.2	0.344
Fasting plasma glucose (mmol/L)	8.5±0.2	8.6±0.4	0.403

Notes: Data are presented as mean ± SD for normally distributed data, as median (interquartile range) for nonnormally distributed data, and as n (%) for categoric variables.

Abbreviations: NAG, N-acetyl-β-d-glucosaminidase; CV, cardiovascular; BMI, body mass index; eGFR, estimated glomerular filtration rate; HDL, high density lipoprotein; LDL, low density lipoprotein.

Table 2 Multivariate Cox Regression Analysis of Predicting CV Events in Patients with Type 2 Diabetes Mellitus (N = 357)

	Crude	Model 1	Model 2
Estimated GFR (mL/min per 1.73 m^2)	1.42 (1.22–1.76)	1.36 (1.18–1.76)	1.32 (1.14–1.68)
P value	0.017	0.019	0.021
Urinary NAG (IU/L)	1.59 (1.31–1.98)	1.47 (1.26–1.89)	1.43 (1.23–1.93)
P value	0.009	0.010	0.015
Urinary NAG (U/g creatinine)	1.64 (1.39–2.62)	1.57 (1.34–2.41)	1.51 (1.31–2.27)
P value	0.002	0.007	0.010

Notes: Model 1: Adjusted for no. Model 2: Adjusted for age, gender, smoking history, drinking history and BMI. Model 3: Adjusted for age, gender, smoking history, drinking history, BMI, systolic blood pressure, diastolic blood pressure and moderate physical activity.

Abbreviations: NAG, N-acetyl-β-d-glucosaminidase; CV, cardiovascular; BMI, body mass index; eGFR, estimated glomerular filtration rate.

Figure 1 Kaplan–Meier analysis for cardiovascular events free stratified by urine NAG.

Table 3 Sensitivity Analysis of Predicting CV Events in Patients with Type 2 Diabetes Mellitus By Adding “Duration of Diabetes” as the covariate (N = 357)

	Crude	Model 1	Model 2
Estimated GFR (mL/min per 1.73 m^2)	1.32 (1.21–1.73)	1.25 (1.18–1.69)	1.23 (1.13–1.64)
P value	0.035	0.40	0.41
Urinary NAG (IU/L)	1.38 (1.25–1.84)	1.33 (1.21–1.76)	1.27 (1.18–1.72)
P value	0.011	0.018	0.023
Urinary NAG (U/g creatinine)	1.43 (1.27–2.35)	1.38 (1.25–2.14)	1.35 (1.23–2.09)
P value	0.007	0.009	0.012

Notes: Model 1: Adjusted for duration of diabetes. Model 2: Adjusted for age, gender, smoking history, drinking history, BMI, duration of diabetes and duration of diabetes. Model 3: Adjusted for age, gender, smoking history, drinking history, BMI, systolic blood pressure, diastolic blood pressure, moderate physical activity and duration of diabetes.

Abbreviations: NAG, N-acetyl-β-d-glucosaminidase; CV, cardiovascular; BMI, body mass index; eGFR, estimated glomerular filtration rate.

Table 4 Stratified Analysis of Predicting CV Events in Patients with Type 2 Diabetes Mellitus By Adding “eGFR ≥ 60 mL/min per 1.73 m²” as the covariate (N = 357)

	Crude	Model 1	Model 2
eGFR ≥ 60 mL/min per 1.73 m^2
Urinary NAG (IU/L)	1.15 (1.03–1.73)	1.08 (0.93–1.58)	1.04 (0.89–1.47)
P value	0.037	0.053	0.157
Urinary NAG (U/g creatinine)	1.06 (0.94–1.87)	1.04 (0.92–1.84)	1.02 (0.88–1.73)
P value	0.146	0.205	0.226
eGFR < 60 mL/min per 1.73 m^2
Urinary NAG (IU/L)	1.53 (1.29–2.93)	1.53 (1.29–2.81)	1.50 (1.27–2.96)
P value	0.010	0.011	0.016
Urinary NAG (U/g creatinine)	1.56 (1.19–2.69)	1.49 (1.17–2.52)	1.44 (1.15–2.49)
P value	0.006	0.008	0.010

Notes: Model 1: Adjusted for duration of diabetes. Model 2: Adjusted for age, gender, smoking history, drinking history, BMI, duration of diabetes and duration of diabetes. Model 3: Adjusted for age, gender, smoking history, drinking history, BMI, systolic blood pressure, diastolic blood pressure, moderate physical activity and duration of diabetes.

Abbreviations: NAG, N-acetyl-β-d-glucosaminidase; CV, cardiovascular; BMI, body mass index; eGFR, estimated glomerular filtration rate.

Table 5 ROC Analysis of Predicting CV Events in Patients with Type 2 Diabetes Mellitus (N=357)

Variables	AUC	Standard Error	95% CI	P value
Estimated GFR (mL/min per 1.73 m^2)	0.74	0.03	0.65–0.93	0.012
Urinary NAG (IU/L)	0.78	0.04	0.68–0.96	0.009
Urinary NAG (U/g creatinine)	0.81	0.05	0.72–0.97	<0.001

Abbreviations: NAG, N-acetyl-β-d-glucosaminidase; CV, cardiovascular; eGFR, estimated glomerular filtration rate; AUC, area under the curve.