Urinary α1-Microglobulin as a Marker of Nephropathy in Type 2 Diabetic Asian Subjects in Singapore

OBJECTIVE: This study examines urinary alpha(1)-microglobulin as a marker of early nephropathy in type 2 diabetic Chinese, Malays, and Asian Indians in Singapore. RESEARCH DESIGN AND METHODS: A cross-sectional study was performed on 590 consecutive type 2 diabetic patients (296 males, 294 females) who were on routine follow-up at a primary care clinic. Information was obtained from interviews, case notes, and blood and urine samples. Because the distribution of urinary alpha(1)-microglobulin levels was highly skewed, these levels were log-transformed, and geometric means were calculated. There was correction for variability in urine flow by dividing by urine creatinine levels, given as mg/mmol urine creatinine, and adjustment for confounding variables. RESULTS: Urinary alpha(1)-microglobulin was higher in men than in women and was directly related to age, but no ethnic differences were apparent. It was directly related to duration of diabetes, with adjusted geometric means of 1.19 and 1.43 mg/mmol urine creatinine for a duration of <10 and > or =10 years, respectively (P = 0.07). Urinary alpha(1)-microglobulin was highest in patients on insulin, followed by those on oral medication and then those on diet alone (adjusted geometric means: 1.47, 1.36, and 0.86 mg/mmol urine creatinine, respectively; P = 0.01). Levels were also higher in patients with poor glucose control, as measured by HbA(1c), fasting plasma glucose, and 2-h postprandial plasma glucose (P < 0.01 for each). Urinary alpha(1)-microglobulin was directly related to albuminuria, with adjusted geometric means for normoalbuminuria, microalbuminuria, and macroalbuminuria of 1.06, 1.47, and 4.72 mg/mmol urine creatinine, respectively (P < 0.01). However, of patients with normoalbuminuria, 33.6% had raised urinary alpha(1)-microglobulin. Likewise, of patients with normal urinary alpha(1)-microglobulin, 27.6% had albuminuria. CONCLUSIONS: Urinary alpha(1)-microglobulin was related to duration, severity, and control of diabetes. Urinary alpha(1)-microglobulin and albumin were directly related, but in some patients, one was present in the absence of the other. Hence, in addition to albuminuria (which measures glomerular dysfunction), urinary alpha(1)-microglobulin (which measures proximal tubular dysfunction) is useful for the early detection of nephropathy in diabetic subjects.