Cadmium-Induced Tubular Dysfunction in Type 2 Diabetes: A Population-Based Cross-Sectional Study

The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of β-microglobulin (βM) above 300 µg/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics ( = 81) and non-diabetics ( = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and βM excretion rates (E and E) to creatinine clearance (C) as E/C and E/C. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold ( < 0.001) and 3-fold ( = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of E/C increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% ( < 0.001) and 15% ( = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, E/C was associated with E/C (β = 0.375, = 0.001) and obesity (β = 0.273, = 0.015). In the non-diabetic group, E/C was associated with age (β = 0.458, < 0.001) and E/C (β = 0.269, < 0.001). However, after adjustment for age, and body mass index (BMI), E/C was higher in the diabetics than non-diabetics of similar E/C ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden.