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

Abstract

OBJECTIVE -It has been reported that diabetes may increase the risk of cadmium-induced kidney damage. The presence of metallothionein antibody (MT-Ab) increased the susceptibility for tubular damage among cadmium workers. This study focused on the relationships between levels of MT-Ab, urinary cadmium, and kidney function in a Chinese type 2 diabetic population. RESEARCH DESIGN AND METHODS-A cross-sectional study was performed on 229 type 2 diabetic patients (92 men and 137 women) who were recruited from two community centers in one district of Shanghai City in China. Information was obtained from interviews, health records, and blood and urine samples.RESULTS -Levels of the tubular biomarker ␤ 2 -microglobulin increased significantly when the levels of MT-Ab and urinary cadmium were elevated in male and female subjects; in contrast, the levels of urinary albumin, a glomerular biomarker, did not display such a pattern. After adjusting for potential confounding covariates, logistic regression showed that the odds ratios (ORs) of tubular dysfunction increased upon 1) increasing the MT-Ab concentration from a low to high level ) and 2) increasing the level of urinary cadmium from Ͻ1 to Ն1 g/g creatinine (3.34 [1.17-9.53]); the OR of patients currently smoking was 3.51 (1.14 -10.80) relative to that of those who had never smoked.CONCLUSIONS -This study proves that the presence of MT-Ab can potentiate tubular dysfunction among diabetic subjects and that patients with high MT-Ab levels are more prone to development of tubular damage. Diabetes Care 29:2682-2687, 2006T he incidence and prevalence of diabetes are rising globally. It is predicted that the number of patients worldwide with diabetes will reach 366 million by the year 2030, with 42 million of them residing in China (1). For patients with diabetes, kidney disease is a dreaded complication. Currently, the susceptibility to toxic hazards in populations at high risk is of increasing concern. In such high-risk groups, diabetes is one condition that can be suspected of increasing the susceptibility to toxicants.Cadmium is a well-known nephrotoxic agent with an extremely long biological half-life of 15-30 years in humans (2). From some cross-sectional population studies, it was reported that diabetes could augment the risk of cadmiuminduced renal damage, especially tubular dysfunction (3,4). Several experimental studies have demonstrated an increased susceptibility toward cadmium nephrotoxicity (5,6) in spontaneously diabetic mice and hamsters, when compared with normal animals of the same strain. Streptozotocin-induced diabetic rats are more susceptible to cadmium nephrotoxicity than are normal rats when they are exposed subchronically to cadmium chloride in drinking water (7,8).Metallothioneins (MTs) comprise a family of stress proteins that contain a high content of cysteine and divalent metals. Several physiological roles have been proposed for MTs, including detoxification of toxic heavy metals, e.g., cadmium, homeostasis of essential metals, e.g., zinc and co...

Early biomarkers of cadmium exposure and nephrotoxicity

“…The urinary excretion of Cd and metallothionein have been used both as markers of Cd exposure and of Cdinduced proximal tubule injury (Bernard 2004;Chen et al 2006c;Mueller et al 1998;Shaikh and Smith 1986;Shaikh et al 1987). The typical patterns for the urinary excretion of Cd and metallothionein are illustrated by the animal data shown in Fig.…”

“…For population monitoring, a cutoff value of 300 lg/g b 2 -microgobulin creatinine has been used (Huang 2004;OSHA 1999). Other investigators have recommended lower critical exposure levels or bench mark dosage levels (BMDL) derived from mathematical models that are based on doseresponse data and reflect levels of Cd exposure that do not result in adverse health effects (Chen et al 2006c;Uno et al 2005). Even though b 2 -microglobulin has proven to be a very useful biomarker, its lack of stability in acidic urine can be problematic.…”

Possibilidade do uso de Mexilhão Dourado contaminado com metais tóxicos em dietas para frangos de corte

“…Esta possui baixo peso molecular e capacidade de se ligar com até sete átomos de Cd, os quais são transformados em forma biologicamente inativa e acumulados no organismo. Atualmente, esta proteína é o principal mecanismo de defesa dos animais em relação ao Cd (CHEN et al, 2006).…”

Cadmium: An Environmental Heavy Metal with Nephrotoxic Potency, Especially in Diabetic Population

“…In a cross sectional study among 229 Chinese type 2 DM patients, Chen et al 28 had proved that the presence of metallothionein antibody (MT-Ab) can potentiate tubular dysfunction among diabetic subjects and the patients with high MT-Ab levels are more prone to develop tubular damage.…”