Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

Abstract

BackgroundIt has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. AimTo test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). MethodsAll 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. ResultsThe mean B-Cd (n=590) was 0.53µg/L (median 0.34µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56µg/L) and DM (point estimate +0.40mg Alb/12h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15mg/12h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT regarding effect of B-Cd on eGFR or RBP. ConclusionThe present study provides support for the hypothesis that women with DM have higher risk of renal glomerular damage from cadmium exposure compared to women without DM.