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 2 -microglobulin (β 2 M) 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 ( n = 81) and non-diabetics ( n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and β 2 M excretion rates (E Cd and E β2M ) to creatinine clearance (C cr ) as E Cd /C cr and E β2M /C cr . Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold ( p < 0.001) and 3-fold ( p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of E Cd /C cr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% ( p < 0.001) and 15% ( p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, E β2M /C cr was associated with E Cd /C cr (β = 0.375, p = 0.001) and obesity (β = 0.273, p = 0.015). In the non-diabetic group, E β2M /C cr was associated with age (β = 0.458, p < 0.001) and E Cd /C cr (β = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), E β2M /C cr was higher in the diabetics than non-diabetics of similar E Cd /C cr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden.