Abstract
Urinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.
Highlights
The health and economic burden of diabetic kidney disease (DKD) has increased significantly due to its strong association with cardiovascular disease and end-stage renal disease[1]
A distinctive pattern was observed between log-Urinary N-acetyl-β-D-glucosaminidase (uNAG) and log-uACR in terms of age and diabetes duration: elevated log-uNAG was more closely associated with older age, whereas log-uACR was positively correlated with longer duration of diabetes
When log-uNAG level was added to the conventional risk factors including log-uACR, age, sex, body mass index (BMI), diabetes duration, angiotensin blocker use, fasting plasma glucose, and hemoglobin level, its discriminatory performance significantly improved from area under the curve (AUC) 0.699 to 0.748 (P = 0.043)
Summary
The health and economic burden of diabetic kidney disease (DKD) has increased significantly due to its strong association with cardiovascular disease and end-stage renal disease[1]. A more sensitive marker that can reflect subclinical kidney damage due to glucose dysregulation is needed to improve the risk stratification and monitoring of DKD in T1D patients in the early stages of DKD. In a nested case-control study of T1D patients with early DKD in the Diabetes Control and Complications Trial (DCCT), uNAG and submicroalbuminuric albumin excretion rate predicted the onset of micro- and macroalbuminuria, independent of each other[7]. Postprandial hyperglycemia and glycemic excursion has been postulated as a distinctive, crucial pathogenesis of micro- and macrovascular complications[15] It remains unclear whether elevated uNAG level is associated with high G/A ratio among T1D patients with early stage DKD. We further investigated whether the measurement of uNAG might have additive discriminatory value for the identification of T1D patients at risk for progression of DKD, in addition to conventional risk factors such as hyperglycemia and albuminuria
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