title: Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women.
abstract: BACKGROUND
  It 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.
  
  
  OBJECTIVE
  To 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).
  
  
  METHODS
  All 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.
  
  
  RESULTS
  The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg 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 (>15 mg/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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg P.O. Box 414, SE-405 30 Gothenburg, Sweden. Electronic address: lars.barregard@amm.gu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Barregard
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Electronic address: goran.bergstrom@wlab.gu.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Electronic address: bjorn.fagerberg@wlab.gu.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
mesh_terms: D000418:Albumins / Q000378:metabolism; D002104:Cadmium / Q000009:adverse effects / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D016017:Odds Ratio; D013548:Sweden
chemical_list: D000418:Albumins; D002104:Cadmium
keywords: Albumin; Cadmium; Estimated glomerular filtration rate; Kidney; Retinol-binding protein; Type 2 diabetes