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

Abstract

SING-LIN LING, MBBS, MSC 2OBJECTIVE -This study examines urinary ␣ 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 ␣ 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 ␣ 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 Ͻ10 and Ն10 years, respectively (P ϭ 0.07). Urinary ␣ 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 ϭ 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 Ͻ 0.01 for each). Urinary ␣ 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 Ͻ 0.01). However, of patients with normoalbuminuria, 33.6% had raised urinary ␣ 1 -microglobulin. Likewise, of patients with normal urinary ␣ 1 -microglobulin, 27.6% had albuminuria.CONCLUSIONS -Urinary ␣ 1 -microglobulin was related to duration, severity, and control of diabetes. Urinary ␣ 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 ␣ 1 -microglobulin (which measures proximal tubular dysfunction) is useful for the early detection of nephropathy in diabetic subjects.

Plasma Metallothionein Antibody, Urinary Cadmium, and Renal Dysfunction in a Chinese Type 2 Diabetic Population

“…It is interesting to note in the present study that the prevalence of tubular dysfunction only (with ␤ 2 -microglobulinuria but without albuminuria) reached 7% (Table 2). This finding indicates that both glomerular and tubular dysfunctions were involved in diabetic nephropathy, which is in accordance with the results of a previous study conducted in Singapore (21). The results suggest that greater emphasis should be placed on tubular dysfunction within the diabetic population, although diabetic renal damage is manifested primarily as glomerular dysfunction.…”

Study of Diabetic Hypertensive Nephropathy in the Local Population of Pakistan

“…Decreases level of this protein affect immunocompetence in diabetic renal disease remains unstudied. The other component of AMBP protein, 1-microglobulin, in urine was directly related to progressive albuminuria in Chinese, Malays, and Asian Indians with type 2 diabetes (Hong, C. Y., et al 2003). This is in contrast to the decreasing levels of this protein observed in our study.…”

Novel Biomarkers for Early Diagnosis and Progression of Diabetic Nephropathy

“…Another interesting study showed that urinary α 1 MG excretion was not increased significantly between normoalbuminuric diabetic patients and healthy controls (Kalansooriya et al 2007). These findings suggested that urinary RBP and α 1 MG measuring proximal tubular dysfunction could be useful markers for the early detection of DN (Hong et al 2003) complementing markers of glomerular dysfunction such as albumin rather than outperforming it (Matheson et al 2010). Conversely the use of β 2 MG for the detection of DN may be more uncertain.…”

“…Urinary RBP (Lapsley et al 1993) and α 1 MG were elevated in diabetic patients with normal UAE (Hong et al 2003). Urinary RBP excretion increased concomitantly with that of NAG in type 2 diabetic patients (Shimizu et al 1992), and urinary α 1 MG levels have been associated or correlated with both transferrin(O'Donnell et al 1991) and albumin (Hong et al 2003) excretion (two markers of glomerular damage). Another interesting study showed that urinary α 1 MG excretion was not increased significantly between normoalbuminuric diabetic patients and healthy controls (Kalansooriya et al 2007).…”